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COMMUNITY OF SANT’EGIDIO
D R E A MDrug Resource Enhancement
against AIDS and Malnutrition
Treating AIDS in AfricaA model for introducing antiretroviral treatment
of HIV into healthcare systems in limited resource countries
L E O N A R D O I N T E R N AT I O N A L
TREATING AIDS IN AFRICA
DREAM, a total-approach program for treating AIDS in Africa,has been active in the field since March 2002, after two years ofpreparation work. Given its innovative approach, including anti-retroviral therapy, and its initial choice of Mozambique – a coun-try with low economic resources – as its institutional partner, rais-ing the funds needed to start up and develop the project has be-come a central problem.Time and funding have been the two poles – at times conflicting –within which we have acted, in the need to get the infrastructure,professional figures, and intervention models into the field withthe urgency that the pandemic and lack of therapy demand.This is why DREAM was started with scant initial funding, suffi-cient for the first phase but not for its development: in the hopeand conviction of being able to attract more substantial resourcesonce the entire project becomes more understandable, effective,and verifiable on the field. And this has happened.DREAM would not have been possible without a prompt openingof credit – at times of small proportions and at times more sub-stantial – and trust from sponsors of all kinds that, although con-tributing in different amounts, were each for their own part im-portant in subsequent development phases: UniCredito Italiano,Trenta Ore per la Vita, Sue Ryder Care, Fondazione Monte deiPaschi di Siena, Generalitat de Catalunya, Messaggero di Sant’An-tonio, Zecchino d’Oro, Dopolavoro Ferrovie dello Stato, Accen-tus, Viva gli Anziani, Il Paese dell’Arcobaleno, Regione Campania,Regione Emilia Romagna, CEI, Action Medeor, Ferrovie dello Sta-to, Farmindustria, Misericordia di Siena, Caritas tedesca, Flan-ders, GTZ, Fons Català de Cooperaciò al Desenvolupament, Co-muni dell’Umbria per l’Africa, the Finnish Embassy in Mozam-bique, Wine for Life, Merck Sharp e Dohme Italia, the Province ofNaples and Rissho Kosei-Kai.DREAM’s main sponsor is UniCredito Italiano – a partnership de-cisive for the whole program’s rapid development on Mozambicanterritory. This solid, transparent joint venture of broad socialreach is a centrepiece for other alliances and collaborations thatare now enabling DREAM to grow quickly, yielding important re-sults for the population of Mozambique and for similar projects inother countries in sub-Saharan Africa.Many common citizens have also made their contribution to mak-ing DREAM a dream come true.Therefore, on behalf of all Mozambicans, and of all those who willbenefit from the DREAM program elsewhere in Africa in the fu-ture, we would like to thank:
UniCredito Italiano – Main Sponsor
Trenta Ore per la Vita
Sue Ryder Care
Fondazione Monte dei Paschi di Siena
Generalitat de Catalunya
Messaggero di S.Antonio
Lo Zecchino d’oro
Dopolavoro Ferrovie dello Stato
Accentus
Viva gli Anziani
Il Paese dell’Arcobaleno
Action Medeor
Farmindustria
Flanders
The Finnish Embassy in Mozambique
Fons Català de Cooperaciò al Desenvolupament
Wine for Life
Ferrovie dello Stato
Rissho Kosei-KaiRKK
Community of Sant’Egidio
D R E A MDRUG RESOURCE ENHANCEMENT
AGAINST AIDS AND MALNUTRITION
TREATING AIDS IN AFRICAA model for introducing antiretroviral
treatment of HIV into healthcare systems in limited resource countries
Maria Cristina MarazziMichelangelo Bartolo
Ersilia BuonomoSusanna Ceffa
Stefano CapparucciAndrea De Luca
Leonardo Emberti Gialloreti Fulvio Erba
Paola GermanoGiovanni GuidottiGiuseppe Liotta
Massimo Magnano San LioLeonardo Palombi
Elio PittiglioGraziella Tintisona
Many thanks for the original contribution to the elaboration ofthe contents of this handbook to:
Noorjeah Abdel Magid, Marco Calgaro, Giuseppe Dardo,Sandra Loureiro, Pasquale Narciso, Carlo Federico Perno,
Stefano Vella, Kriesten Wouters, Sergio Benedetti.
L E O N A R D O I N T E R N AT I O N A L
© Copyright 2003 Leonardo International s.r.l.© Copyright 2003 Comunità di Sant’Egidio
Leonardo International s.r.l.Viale Majno 24 – 20129 MilanoTel. 02 76318720 – Fax. 02 76318728www.leonardointernational.comwww.santegidio.org
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The Community of Sant’Egidio
The Community of Sant’Egidio began in Rome in 1968, inthe period following the Second Vatican Council. Today it isa movement of lay people and has more than 40,000 mem-bers, dedicated to evangelisation and charity, in Rome, inItaly and in more than 60 countries throughout the world.The Community of Sant’Egidio is a “Church public lay as-sociation”. The different communities, spread throughoutthe world, share the same spirituality and principles whichcharacterise the way of Sant’Egidio:Prayer, which is an essential part of the life of the communi-ty in Rome and in communities throughout the world. Prayeris central to the overall direction of community life.Communicating the Gospel, the heart of the life of the Com-munity, which extends to all those who seek and ask for ameaning for their life.Solidarity with the poor, lived as a voluntary and free serv-ice, in the evangelical spirit of a Church that is the “Churchfor all and particularly the poor” (Pope John XXIII).Ecumenism, friendship, prayer and search for unity amongChristians of the whole world.Dialogue, recommended by Vatican II as a way of peace andco-operation among religions, and also a way of life and asa means of resolving conflicts.The Community has as its center the Roman Church of San-t’Egidio, from which the Community takes its name. Fromits very beginnings, the Community has maintained, in thearea of Trastevere and in Rome, a continuous presence ofprayer and welcome for the poor and for pilgrims.
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The Community of Sant’Egidio is a Non-Governmental Or-ganization (NGO) headquartered in Rome and active on allcontinents, with programs including development coopera-tion in support of human rights, and supporting and facili-tating peace and reconciliation processes. Amongst NGOs,the Community of Sant’Egidio is known for the total com-mitment (96-98%) of its resources to the projects, and thevery low overhead and expenses for supporting the struc-tures (2-4%). This is made possible by the free, voluntarywork of all the directors and many of the highly profession-al and specialized employees. This is why all the Community’s programs have an extremelylow overall cost in comparison with their impact and results.The Community of Sant’Egidio has a long history in Mozam-bique, from the humanitarian aid sent in the early 1980s tothe official mediation between the guerrillas and the govern-ment leading to the General peace agreement signed in Romeon 4 October 1992 after 27 months of negotiations. Today,Mozambique is a major example of democratic rebirth insub-Saharan Africa.This special link with Mozambique has led the Communityof Sant’Egidio to choose this country as the first where topilot the Global Program to fight AIDS in Africa, calledDREAM (Drug Resource Enhancement against AIDS andMalnutrition).
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Why DREAM?DREAM (Drug Resource Enhancement against AIDSand Malnutrition) is a control, prevention, and treatmentprogram – in other words, a global program to fight HIVinfection in limited resource countries.
DREAM reflects the Community of Sant’Egidio’s way ofthinking
The Community of Sant’Egidio places central importanceon the person and on each and every life. For many longyears, an exclusively prevention-based strategy has been theparadigm of all large international agencies – and of the sci-entific community – for attacking AIDS in developing coun-tries. This strategy has shown its limits: tens of millions ofHIV positive Africans and the epidemic’s alarming growthcurve (steady until at least 2010) require extraordinary ef-forts to recover lost time and, at last, to allow prevention tobe accompanied by therapy; this is the only way to avoidthat the entire struggle against AIDS in the southern areas ofthe world fail, and much of Africa, today and tomorrow,disappear. The program was therefore created with the ob-jective of going back to bringing prevention and therapy to-gether, convinced that we must save as well as prevent, gain-ing new time to live for as many people as possible.
DREAM: conceived for excellence
Excellence in care, and in diagnosis, organization, and infor-mation. Thus, as will be illustrated in the following pages,
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DREAM proposes to apply in Africa the state of the art ofWestern standards, by using viral load evaluation routines, orby introducing the Highly Active Anti-Retroviral Therapy(HAART), the current gold standard in HIV treatment, forall patients that need it. For the Community of Sant’Egidio,people are never simple “emergencies” – bodies to beclothed, sores to treat, mouths to feed. They are always peo-ple, always friends. This is why we are guided by that simple,age-old secret: do unto others as we have them do unto us.Who wouldn’t want excellence for himself? This approach isprofoundly efficient: it provides great motivation for the per-sonnel involved; it earns maximum patient collaboration; itmakes the patients themselves promoters of knowledge in thesurrounding environment; it eliminates waste and interrup-tion of the therapy in progress; and it raises the quality of theservice that is offered. In the area of AIDS, the minimalism ininternational aid and cooperation so often proposed risks re-sulting in perilous – if not outright lethal – consequences inan environment already exposed to too much weakness andin the face of a complexity that at root resists any sector-based or reductive approach.
DREAM: based on partnership
The Community of Sant’Egidio does not have the role of adistant donor that, by its ownership, grants its funds and letsthings be, seeing mostly to the financial reports: not a pa-tronizing approach but rather a responsible one. Being ableto work together provides yet another opportunity. Workingtogether means supplying all the means necessary for achiev-ing the objectives, in collaboration with – and with respectfor – the local institutional framework. Thus, while hundredsof the Community’s members are devoted to activities pro-moting the project in the West, more than 120 qualified vol-unteers – physicians, nurses, lab technicians, computer ex-perts, educators, and administrators – work in rotation, withoverlapping and direct transfer of knowledge, all year long,alongside the local personnel involved in the program.
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DREAM: a participatory program
Although it was created only in the world’s more industri-alized nations, DREAM has a rock-solid social base inAfrica; in Mozambique, a country counting more than 60Sant’Egidio communities, for instance, there are five thou-sand youths and adults working alongside the most impov-erished. Everyone lends a hand: no one is so poor as to beunable to help someone even poorer. These communitiesare active in the program in two strategic areas: health edu-cation and nutritional support. Tens of thousands ofMozambicans in the most deprived areas draw stable bene-fits from this daily activity. But DREAM is also open to par-ticipation from those living in the West. While scientific in-stitutions and various subjects from the industrial and eco-nomic world have become stable partners in the program,offering their scientific and economic resources, a largenumber of private citizens are also taking part in the pro-gram, receiving detailed information and providing theirsupport in many ways.
DREAM: modulated for rapid scaling–up
Excellent services along with reduced economic resourceshave not set a limit on the possibility of bringing treatmentto a vast number of people and, in the future, to all. Themain problem lies rather in the difficulty of implementing, inlimited-resource healthcare systems such as those in Africa,the complex assistance required for HIV/AIDS. An innova-tive road in this field must be built, taking these special fea-tures into account and satisfying the need for light, agile fa-cilities. DREAM has now shown itself to be a functioningmodel that must face the challenge of its growth. The issueis to broaden and spread all the system’s aspects together,one alongside the other, from training technical and medicalpersonnel (in countries, with a chronic shortage of personnelaggravated by the pandemic) to creating suitable infrastruc-tures; from diagnostic facilities to suitable assistance in
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childbirth; and from monitoring and supervising therapiesto evaluating the results. Co-ordinated, harmonious growthof the various components is critical and requires exception-al commitment, now and in the future. And in any event, thefight against AIDS must come to grips with this inescapablelarge-scale transit of therapies if it is to aim to become a na-tion-wide battle and, later, a model for limited-resourcecountries. Indeed, it is impossible to offer everything toeveryone at the same time. This requires priority-setting.Thus, in the first phase, DREAM has given precedence topregnant women, single mothers, and some key interven-tions in such strategic sectors of development as healthcare(physicians, nurses, and auxiliary personnel) and education(teachers at mandatory school). Program directors havebeen frequently asked whether it is ethical to privilege onepopulation segment over another. But unfortunately, thestarting situation in much of Africa is that of non-choice ac-companied by immobility, impotence, and total resignationbefore the expanding epidemic.Not choosing in order to avoid the ethical risk of choosingthe necessary priorities at the start of any program withglobal ambitions (like those of containing, combating, anddefeating AIDS in Africa) truly opens up the very opposite tothe ethical risk, in a sort of ethical limbo that is responsiblefor the disappearance of entire generations.This is why priority-setting introduces a starting ethic in adramatically marked north/south imbalance.DREAM has not forgotten other population sectors withdifficulty accessing treatment, such as prison inmates orchildren in institutions. It is thus rapidly expanding in cen-tral and northern Mozambique and across Africa.
DREAM: a public health program
DREAM has been conceived to become a stable componentof national healthcare systems. In Mozambique, for instance,its facilities – at hospitals, healthcare centers, and maternitywards – are those of the healthcare system. And already lo-
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cations will also include private facilities of great public andsocial importance – managed by religious congregations,NGOs, and other solidarity agencies – which are already ef-fective in helping scale up the program. All healthcare servic-es, from diagnosis to nutritional support, from health educa-tion to conventional therapy for opportunistic and sexuallytransmitted infections (like HAART) are offered completelyfree of charge, at least for the populations in the centers’ userbasins. The possibility is being studied of guaranteeing accessto these services for those farther away geographically, andcost-sharing mechanisms based on out-of-pocket expenseshave been proposed, to cover the costs of diagnosis reagents,for example.
DREAM: an operating research project
DREAM is also used for the purposes of research in publichealthcare, epidemiology of services and their impact, in clin-ics, and in therapy in developing countries. The acquisition ofnew knowledge in research dedicated to development inter-ventions in impoverished countries is a sound contribution inthe fight against AIDS. In this sense, the program has strongconnections with the scientific world and is oriented towardsgathering data for epidemiological and clinical studies, bothas routine and for ad-hoc investigations. Much attention hasbeen given to the need to give life to an efficient internal com-munications system. A computerized, wired network links allthe centers and connects them to servers on site and in Eu-rope, thereby facilitating the coordination and supervisionwork, allowing immediate remote consultation for DREAMclinics, and providing the data produced by the individual fa-cilities in real time.These pages were written for two reasons. The first is to pro-vide simple, detailed information about the first steps andconquests of a program that has shown convincingly – andagainst the grain – that AIDS can be defeated in Africa. Thesecond is that DREAM aims to be an open channel for thosewho wish to take part in this engaging battle but lack the
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means to do so – a collector of energy and resources for allof Africa. And in fact, DREAM – and this is its last charac-teristic – needs everyone and is available to those who thinkthey can expand it to other situations in the struggle againstAIDS in Africa.Defeating AIDS in Africa is really possible. We hope thatawareness of this can become contagious, spreading amongthose who can multiply the effectiveness of this decisive bat-tle for the future of Africa and of the whole planet.Support from many people makes it possible to grow betterand faster. And against AIDS, time is of the essence.
Even as these pages are printed, DREAM has been active formore than a year, and the first results were presented at theTenth CROI (Conference on Retroviruses and Opportunis-tic Infections - Boston 2003).
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Chapter 1
DREAM: the program
1. The human immunodeficiency virus pandemic
Starting in the early 1980s, AIDS had a development with-out comparison in the history of human pathologies. WithAIDS, something new and hitherto unheard of was develop-ing in the world. And the tens of millions of people strickenin every country in the world bear witness to a pandemicthat can truly lay claim to being the first pathology of the eraof globalization.A radically new situation such as this requires radically newresponses. Models must be identified that take into accountboth the features of the illness and the available possibilitiesfor treatment.More than two thirds of those with HIV/AIDS – tens of mil-lions of people – live in Africa. And only a very small numberof these people, mostly those with some economic means,have access to antiretroviral treatment. With such a seriousemergency, while intervention must be quick, what is neededimmediately is to start laying the foundations for building amedium- and long-term response.
2. Antiretroviral therapy
The advent of HAART (Highly Active Anti-RetroviralTherapy) in the mid-1990s radically changed the naturalhistory of the illness, transforming AIDS into a chronicpathology. But at the same time, antiretroviral therapy cre-
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ated new needs. To yield optimum results, this therapy re-quires technologically advanced monitoring and diagnosticmethods, and must reach the population extensively, whereit lives. The availability of highly specialized centers mustbe combined with the greatest possible spread and accessi-bility. Here is the first contradiction – one apparently diffi-cult to solve, because the impact of the therapeutic inter-vention can only be limited. In brief, here lies the challenge:treatment with antiretrovirals must be based on advanceddiagnostic methods, by necessity localized in a large city; atthe same time, to be effective, treatment has to rely on ex-tensive distribution.Over time, it became clear that AIDS could not be foughtwith prevention alone; treatment was needed as well. Ongo-ing prevention is as necessary as ever, but on its own, it isclearly not enough. In fact, the lack of hope for access to andavailability of therapy risks drastically to reduce the effec-tiveness of prevention, thereby lowering interest in knowingones own condition vis-à-vis the infection: awareness with-out an available therapy would risk creating the dramaticand unbearable knowledge of a premature demise, oftenpreceded by isolation and social condemnation.These needs imply wide-ranging economic and political in-terventions, as well as highly articulated and innovativehealthcare planning and organization of services. The mil-lions of deaths, infected persons, and orphans require imme-diate intervention, without getting bogged down in non-es-sential preparatory phases. Likewise, however, the emer-gency intervention should be designed from the beginningwith a view to developing stable facilities capable of wagingthe battle over the long term. To put it briefly, interventionin the struggle against AIDS must be based on immediacyand farsightedness.
3. A public health intervention
It was starting from these assumptions that the Communityof Sant’Egidio developed its methodology in the fight against
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AIDS, which in Mozambique is already expressed throughthe DREAM Program. This horizontal public health inter-vention aims to take action in the various areas of the coun-try. To be quickly operative and effective in order to respondto emergencies, DREAM has created a bureaucratically andadministratively streamlined intervention model. This partic-ularly agile system makes it possible to maintain administra-tive costs – including those for non-local personnel, whowork exclusively free of charge – at a minimum percentage ofthe overall budget at all times. In other words, the wholebudget is used exclusively to fund activities in the country.
Day hospital and home assistanceAntiretroviral therapy is administered to the populationthrough day hospital and home assistance activities. In thisway, lacking specialized facilities spread throughout the ter-ritory, the program is allowed to be in direct contact withthe population, thereby guaranteeing the necessary controlover the therapy. When the people to be treated cannot comecloser to the possibility for therapy, it is DREAM that bringsthem closer.However, AIDS cannot be combated exclusively with anti-retroviral drugs. It requires a more wide-ranging interven-tion taking into account the person’s overall needs. Thepackage of services ordinarily offered to the patient on a sta-ble basis is comprised of voluntary counseling and testing,lab tests (biochemical, haemochrome, CD4+, and viralload), antiretroviral therapy, treatment of opportunistic in-fections and sexually transmitted diseases, nutritional sup-port, basic health education, and social support.
Caring for mothers and prevention of vertical transmissionAn original aspect of the DREAM program is caring forpregnant women in accordance with the Mother & ChildPrevention & Care (MCPC) scheme. Pregnant HIV positivewomen are given the following services:Evaluation of nutritional status and supplementation, wherenecessary, for mother and newborn– Testing & counseling for HIV infection
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– Health education– Diagnosis and treatment of sexually transmitted diseases– Diagnosis and treatment of opportunistic infections– Prophylaxis of mother-to-child transmission with anti-
retroviral drugs– Treatment of the mother in accordance with protocols
with antiretroviral drugs both for treating the HIV infec-tion, and for mother-to-child transmission.
– Support and monitoring of feeding and caring for the new-born
Care for mothers is one of the special features of the modelproposed through DREAM. In fact, the offer of antiretrovi-ral therapy to mothers – which is not interrupted but con-tinues even after childbirth – is essential. It is the only wayfor a mother, who has given birth to a child in which infec-tion has been prevented, from dying of AIDS shortly there-after. Until now, this kind of intervention has not been usedin Africa. On the other hand, it is well known that in Africa,the survival of orphaned children, even HIV negative ones,is lower than that of other children. They also have fewerpossibilities to attend school. Thus, not only is the verticaltransmission of the infection prevented, but a mechanism ofsurvival – and of increased chances for and in life – is creat-ed for the newborn and the entire family.
TrainingDREAM places great importance on training personnel, andhas in fact developed its intervention taking exclusively localpersonnel (physicians, medical technicians, nurses, biolo-gists, lab technicians, and social workers) as its basis. This isone of the essential aspects for the future sustainability ofany intervention. However, the use of local personnel re-quires strong human investment in and commitment to the-oretical and practical training, both on site and abroad. Andthis is what DREAM foresees in the short, medium, andlong term. Given the need to intervene as soon as possible,an ongoing training program has been provided for and pre-pared, right from the beginning. This is why DREAM has
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developed an original model for partnership between localpersonnel and staff from other countries. Non-local person-nel is always present in the country in regular shifts, thusguaranteeing the necessary technical and training supportfor local personnel, without ever replacing it in any way.DREAM has already led a number of training courses forhome care assistants, nurses, and physicians on treating andassisting persons living with HIV. It also organizes publicconferences on issues of treatment and advanced diagnosticsin HIV infection. Several times a year, supervision missionsreserved for the activity of the project’s medical personnelare held.
A major part of personnel training is seeing to thequality of the relationship with the patients, who mustat all times be received courteously, openly, and withrespect. Counseling does not end with the first exami-nation, but continues in subsequent visits through di-rect contact with patients and support to all. Similar-ly, the facilities where patients are treated must alwaysbe well cared for and cleaned in accordance with highhealth and sanitary standards – this also applies to thecase of essential facilities. These are two important as-pects in order to guarantee, in addition to personaldignity, the effectiveness of interventions – such as thatagainst AIDS – that require much time and good col-laboration with the patient.
The laboratoryTo be effective, antiretroviral treatment requires strong labsupport. This is why the DREAM program has included thedevelopment of highly specialized molecular biology labs,where the CD4+ count and the viral load measurement (inaccordance with the indications of the diagnostic and thera-peutic protocols), in addition to the basic biochemistry andhaemochrome, are regularly performed, acting as the tech-nological core of the whole program. Labs of this kind areneeded in order to respond quickly and effectively to the de-velopment of drug-resistant viral strains. This is an invest-
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ment for the country’s future, both in training highly spe-cialized human resources and in equipment.
ComputerizationAll the DREAM program’s activities are monitored througha computer network linking the various centers to one an-other and to the reference labs. This system guarantees effi-cient monitoring of the treated patients – including adher-ence to the therapy – and becomes an important source ofdata that can be used to continue improving the quality ofthe interventions, through applied research too. And it is ap-plied research that makes it possible to perfect the forms ofintervention and helps guarantee that the finest, most effec-tive help is offered, even in sub-Saharan Africa countries.
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Chapter 2
DREAM: protocols for diagnosisand treatment
1. Introduction
In October 2001, the DREAM program began its activitiesto treat persons with HIV/AIDS, opening the first home careand day hospital assistance service in a suburb of Maputo,Mozambique’s capital. With the help of consulting from spe-cialists in the sector, protocols were developed for care withantiretroviral drugs to be used to treat the sick and preventmother-to-child transmission. The issue was to adapt to theparticular situation of a limited resource country likeMozambique those clinical and pharmacological indicationsalready trialled in the United States and Europe that hadcompletely changed the natural history of the disease from1996. In such a way was reduced patient mortality even inthe most advanced phase of infection.Administration of antiretroviral drugs to patients began inFebruary 2002, when these drugs became available inMozambique. The therapeutic protocols developed, which of course can beperfected, have sought to take into account the problemsposed by the context being worked in:– the possibility of using generic drugs in fixed combinationsof three active principles within the same pill: although itlimits the variety of medications and therapeutical schemesthat may be used in comparison with the range available inthe United States and Europe, at the same time it may pro-
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vide an important opportunity to simplify therapy and im-prove adherence;– the high prevalence of such pathological conditions asHIV/TB co-infection, malaria, or simple malnutrition-basedanemia, that condition therapeutic choices;– the percentage of women in childbearing years among theinfected (more than 50% of therapy candidates), which fur-ther conditions therapeutic choices given the possibility ofpregnancies;– the need to blend high patient management standards withcost containment (for lab diagnosis, for example);– the problem of prophylaxis for opportunistic infections(which ones, how many, for how much time, how to avoidexcessive difficulties in taking the therapy);– the frequent need for nutritional support accompanyingtherapy, particularly for pregnant women.1-2-3
These are just some of the questions that accompanied thedevelopment of the protocols which, although still havingample space for improvement, have so far yielded spectacu-lar results and have represented a first, important contribu-tion to the fight against AIDS in developing countries.
The April, 2002 publication by the World Health Organiza-tion of the document entitled: “Scaling up Antiretroviraltreatment in limited resource setting” marked a point of noreturn in the debate on access to care for persons withHIV/AIDS in Africa3. This document was a theoretical refer-ence point, in many cases confirming the orientations thatDREAM had already taken on and provided more points forreflection on treatment for persons living with HIV/AIDS inAfrica.The WHO document had the following objectives:– to increase the use of antiretroviral drugs to meet the needsof persons living with HIV/AIDS in limited resource coun-tries;– to standardize and simplify antiretroviral therapy to per-mit it to be spread widely and easily;– to ensure that treatment is based on the available scientif-ic evidence, to keep the use of protocols far from the finest
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clinical and therapeutical standards from causing damage toindividual patients and fostering the emergence of resistantstrains.The same WHO document saw public health programs asthe framework most suited for achieving the objectives thathad been set. Along with this document, the guidelines forusing antiretroviral therapy in Europe and the United States,and broad examination of the latest scientific literature, con-stituted the scientific background against which DREAM’sprotocols were developed.
2. Eligibility criteria for treatment
When to begin antiretroviral treatment is still an open issue.While there is general agreement concerning patients withless than 200 CD4+/mm3, or with evident symptoms of dis-ease,4-5 this is not true for asymptomatic patients with CD4+greater than 200. It is true however that potentially mortalinfectious diseases, even in non-immunocompromised hosts,are more widespread in Africa than in Europe or the U.S. Anexample may be Malaria which is one of the leading causesof mortality both in HIV positive and HIV negative pa-tients.6 On the other hand the percentage of subjects withCD4+ between 200 and 350, which develops AIDS within 3years is around 38.5% with a peak of 60% when viral loadsare greater than 55.000 copies/ml.7 These considerationsseem to justify the choice of an aggressive approach, whichDREAM considers to be the extension of antiretroviral ther-apy to those patients with CD4+ between 200 and 350 andwith viral loads greater than 55,000 copies/ml.
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Tab
. 1–
Eli
gibi
lity
cri
teri
a fo
r tr
eatm
ent
wit
h A
RV
Dru
gs Cur
rent
EU
and
W
HO
gui
delin
es
DR
EA
M
US
guid
elin
esfo
r L
RS*
Prot
ocol
WH
O c
linic
al
CD
4+
Vir
al L
oad
clas
sifi
cati
onco
unt
Stag
es I
II –
IV
Any
val
ueA
ny v
alue
Tre
atm
ent
Tre
atm
ent
Tre
atm
ent
Stag
es I
-II
< 20
0A
ny v
alue
Tre
atm
ent
Tre
atm
ent
Tre
atm
ent
Stag
es I
-II
200-
350
Any
val
ueT
reat
men
t/O
bser
vati
onT
reat
men
t/ob
serv
atio
nob
serv
atio
n
Stag
es I
-II
> 35
0>5
5.00
0T
reat
men
t/O
bser
vati
onT
reat
men
t/ob
serv
atio
nob
serv
atio
n
Stag
es I
-II
>350
<55.
000
Obs
erva
tion
Obs
erva
tion
Obs
erva
tion
*LR
S: L
imit
ed R
esou
rce
Sett
ing.
28
3. Treatment regimens
In setting up the treatment protocols the following differentaspects (not in order of importance) were taken into account.
The first was related to the choice of drug combinations.Very many exist, but use of no less than three drugs was de-cided since it is the current golden standard in the treatmentof HIV/AIDS patients. Several clinical trials have shown thatdifferent treatment regimens are basically equivalent interms of antiviral potency8 -15.
The second aspect regards simplicity of administration. Thislimits the range of possible choices. Adherence to drug thera-py has always been one of the major problems linked totreatment in Africa since errors in taking the drugs may easi-ly lead to the emergence of resistant strains. Besides their highcosts and the structural flaws in the Health Systems, this isone of the reasons why many consider HIV/AIDS therapy inAfrica as impracticable or unadvisable. There is no doubtthat the patient’s adherence to drug therapy is crucial and caninfluence efficacy of treatment even in those countries wheredrugs have always been available. It is therefore importantthat where the patient is obliged to interrupt taking a drug orsimply forgets to, he/she should interrupt all three drugs inorder to curb the risk of the emergence of resistant strains.Pharmacological preparations which unite all three drugs ina single pill are very important in improving adherence todrug therapy and reducing the risk of antiretroviral resistantstrains. On the one hand treatment is greatly simplified:from many (up to 10-15) pills a day for a European patientdown to two; on the other hand, where treatment is inter-rupted it necessarily involves all three drugs. Moreover thesepreparations, on average, cost twenty times less than thecorresponding treatment regimens schemes in Europe or theU.S saving up to 95%.
The two basic treatment regimens chosen as the first line oftreatment are:
29
1) zidovudine (AZT) 300 mg – lamivudine (3TC) 150 mg –nevirapine (NVP) 200 mg 2) stavudine (d4T) 30 o 40 mg – lamivudine 150 mg – nevi-rapine 200 mg. The annual cost per person of these two regimens is current-ly 330 USD. The choice between these two regimens is based on an ele-ment often present in HIV patients, especially in highly en-demic malaria areas in Africa: a hemoglobin concentrationlower than 8 g/dl would indicate the use of stavudine. Insteadif hemoglobin concentration is greater or a peripheral neuro-logical disorder is present the regimen with zidovudine is pre-ferred. There is also a third possibility i.e. peripheral neuro-logical disorder and anemia together. This infrequent but notimpossible case would require yet another scheme with aba-cavir(ABC) – didanosine(ddi) – nevirapine, for which phar-macological preparations such as those previously mentioneddo not yet exist. Another aspect which in theory influencesthe choice of drugs, even when starting treatment, is tubercu-losis (a problem which will be discussed further on).However, on the basis of an overall widespread anemia inAfrican people the best regimen, without doubt, would bestavudine-lamivudine-nevirapine. In case of failure of this regimen the alternatives are greaterthan those available for the regimen with zidovudine. In facteven the use of abacavir in patients resistant to treatmentwith zidovudine and lamivudine is limited by frequent crossresistance.3
The alternative to nevirapine, i.e. efavirenz (EFV), does notseem feasible due to potential teratogenicity in a patientpopulation where more than 50% are women, all in child-bearing age and not used to taking contraceptives. More-over, further doubts arise when considering the drug’s phar-macokinetics: they show a longer half-life compared to oth-er drugs thus calling for special attention in administrationor interruption.3-5 For the same reason the combinationstavudine-didanosine should not be used unless there are noalternatives, because of some deaths of pregnant womenwho had used the drugs throughout pregnancy16. Finally the
30
use of protease inhibitors seems more appropriate in second-line regimens considering the difficulties linked to greaterdaily amounts of pills (no protease inhibitors have beencombined in a single pill with other drugs).In the future the availability of once-daily drugs combina-tion may lead to reconsider this therapeutic approachSafety: the drugs used are among the best so far used in com-bating HIV infection. Side effects or adverse events are notmany (except for nevirapine) and their toxicity, in most cas-es is spread over time and can be detected even when peri-odical checks are not very frequent. This is very important inthose areas where travel is neither rapid nor simple and con-tact with patients is less frequent than in other areas.
As far as second line regimens are concerned choice dependson the reasons for changing the initial regimen. Reasons arebasically two: allergy or intolerance of some kind and treat-ment failure.
1) Allergy-intolerance-adverse events attributable to one ofthe drugs included in the first line regimen. If nevirapine isresponsible it can be replaced by a protease inhibitor (for ex-ample indinavir (IDV) or Nelfinavir (NFV) or with a thirdNRTI (Nucleoside Reverse Transcriptase Inhibitor) such asabacavir.3
2) Treatment failure: definition of treatment failure can beclinical (development of AIDS-related diseases after ARThas been administered for a time sufficient to restore im-mune functions), immunological (30% fall in number ofCD4+ lymphocytes or return to CD4+ levels prior to treat-ment), or virological (viral load still present after 6 monthsof treatment or, viral load greater than 10,000 copies after 6months of treatment for those patients with a viral load of500,000 copies before treatment).3 Some degree of variabil-ity however exists and must be assessed over time and oneresult only should not influence decisions. Once this is clear,where clinical conditions are stable, evaluation aimed atchanging the therapy should be carried out after at least 6months of treatment.
31
In this case the whole treatment should be changed: possiblealternatives would be zidovudine-didanosine together withindinavir or Nelfinavir, if initial regimen were stavudine-lamivudine-nevirapine. If instead the initial regimen includ-ed zidovudine the alternative regimen would be the triple di-danosine-stavudine-indinavir3.Resistance to antiretroviral drugs represents a substantialthreat for future therapies, due to the cross resistance amongmany of the drugs available. Altough this is a concern fordeveloped countries as well, this issue cannot be a factorlimiting the spread of antiretroviral therapy in Africa. At thesame time, however, the implementation of systems that lim-it the development of cross-resistance will be highly consid-ered, in a way similar to developed countries. Among them,quick therapy switch at the time of early failure, that is be-fore mutations conferring resistance to antiretroviral drugsare fully developed, is the main criterium. Implementation ofsystems to detect resistance mutations (from simple andeasy-to-use methods, to sophisticated methodologies basedupon sequencing) represents an objective for future efforts.
As far as prophylaxis of opportunistic infections is concerned,the only treatment in the protocol is administration of co-tri-moxazole daily for 6 months in patients with less than 200CD4+ at enrollment. No other kind of prophylaxis is at the mo-ment considered without further details on prevalence of op-portunistic infections in AIDS patients in sub Saharan Africa.The treatment protocol thus designed looks simple and ho-mogeneous. Candidates for treatment are almost all peoplewho have not received any previous antiretroviral treatment.Therefore efficacy is potentially greater than that reported forthe same treatment in European or North American patientswho had previously received different regimens which laterturned out to be sub-optimal. Such efficacy may already beobserved from the first results of the treatment in cohorts ofAfrican patients who have had the opportunity to receive it.17-19
Homogeneity and treatment on a large scale would furtherhelp to combat the emergence of resistance since the patientstend to take always the same drugs.
32
Tab. 2 – Treatment Regimens included in the DREAM protocols
First Line Second Line due to Second line dueallergy/adverse events to treatment failure
d4T – 3TC – NVP d4T – 3TC – IDV AZT – ddI – IDVd4T – 3TC – NFV AZT – ddI – NFVd4T – 3TC – ABC ddI – ABC – IDVAZT – 3TC – NVP ddI – ABC – NFV
AZT – 3TC – NVP AZT – 3TC – IDV ddI – d4T – IDVAZT – 3TC – NFV ddI – d4T – NFVAZT – 3TC – ABC ddI – ABC– IDVd4T – 3TC – NVP ddI – ABC– NFV
4. Caring for the mother and preventing vertical transmission
If the main aim of treatment in people with HIV/AIDS is tocontrast the progression of infection, in pregnant womenwith HIV the aim is also to avoid transmission to the fetus.In this respect viral load is even more important. It is in factthe key element in the risk of infection being transmittedfrom mother to child although it is not clearly the only one.Other risk factors include malnutrition, Sexually Transmit-ted Diseases (STD), genital ulcers, prolonged rupture ofmembranes, vaginal laceration and postnatal feeding.3-20-26
All these elements must be considered and action takenwhere possible.In order to significantly reduce transmission risks, the viralload must be cut down to less than 1,000 copies per ml.1
With highly efficient treatment such as with the three-drugcombination an average reduction of at least one log permonth of treatment of the viral load may be obtained.19 Thismeans that average antenatal treatment should be carriedout for two months or more to be reasonably sure that theviral load in most cases will fall below the 1,000 copies perml. Another aspect to be considered is proneness to pre-termdelivery of HIV positive women. On the basis of all this, be-ginning of treatment at week 25 has been decided for allwomen. For those women who at enrollment present CD4+counts less than 200/mm3, or a viral load greater than55,000 copies/ml (DNA 3.0), or symptoms (WHO clinical
33
staging system level 3), treatment shall commence beforeweek 25 but always after week 14 of pregnancy.Choice is based on much of the same criteria as those al-ready mentioned for adults/adolescents. The chosen regimenis zidovudine-lamivudine-nevirapine due to greater experi-ence acquired in the use of these three drugs in pregnancy. 1
In women with less than 8 mg/100 ml of hemoglobin stavu-dine is preferred. The latter has been involved in three casesof death of pregnant women due to lactic acidosis; in all,three cases the patient had been taking the drug togetherwith didanosine since the beginning of pregnancy16 Othercases of lactic acidosis have been reported for other NsRTIdrugs with or without stavudine but none were lethal.3-16-27
Lactic acidosis is a rare event which may occur in pregnantwomen treated with this kind of drug. However since this israre, staduvine should be maintained as an option in treat-ment to prevent mother to child transmission. However, un-less there is no alternative, association with didanosineshould be avoided. The same considerations may be made inthe case of NRTI-related mitochondrial toxicity except thatno cases of death due to mitochondrial toxicity have beenreported in the literature following use of these drugs.28-31
During pregnancy, the mother receives nutritional support(rice, beans, oil, sugar) and multivitamin supplementation inorder to combat malnutrition and anemia, to reduce theproportion of pre-term deliveries (vitamine A) and the qual-itative and quantitative incidence of low birth weight. More-over, if the proteic and energetic strain induced by HIV onthe body is considered, supplementation plays a fundamen-tal role in the battle against the virus.31-34
Within 72 hours of birth, the newborn receives one dose ofnevirapine syrup to protect it during breastfeeding, in whichhe/she is most vulnerable.Pharmacological treatment is continued at full dosages afterchildbirth in women who, upon enrollment, correspondedto the therapy criteria identified by the DREAM program(see above). Should this condition not exist, therapy is sus-pended a month after childbirth, if it is certain that thewoman has lost her milk. To create safe feeding conditions,
34
women are provided with a filter for water (ceramic and ac-tive charcoal), a bottle and, periodically, the amount of arti-ficial milk the child needs. Brief health education coursesduring pregnancy and individual instruction at childbirthhave the objective of fostering formula feeding. The mothercontinues to receive nutritional and vitamin support duringthe post-partum period. From the 4th - 6th month, weaningbegins, to be completed by about the 12th month.
Saving the future of AfricaCaring for mothers is one of the special features of themodel proposed through DREAM. Offering antiretro-viral therapy to mothers with the objective of curingthem even after childbirth is essential. It is the only wayto prevent the exponential increase of orphans.HIV orphans are already estimated at about 14,000,000– of whom 11,000,000 live in sub-Saharan Africa. Beingorphaned in Africa is not simply an unfavorable condi-tion from a psychological or from a human standpoint.It is a risk factor: the risk of dying more easily than oth-er children, and the risk of not going to school becausethe family cannot manage to guarantee what is neededfor enrolment. In southern Africa, the percentage of or-phaned children attending school falls on average byabout two thirds.DREAM’s choice to offer mothers both prevention formother-to-child transmission and treatment for theirdisease also has the effect of ensuring better adherenceto the program. For prevention projects to work, a mes-sage has to be spread out among people in general andwomen in particular: the desire to fight against AIDS,and above all the hope that this struggle can be won.Now that this is possible at relatively contained costs,care for the mothers is not just an ethical imperative.It makes good sense.
35
Tab
. 3–
Trea
tmen
t re
gim
ens
for
prev
enti
on o
f ve
rtic
al t
rans
mis
sion
Typ
e of
pat
ient
Stag
es 3
- 4
§St
ages
1 -
2§
Stag
e 0+
Ant
e na
tal
II Q
uart
er
Wee
k 25
AZ
T 3
00 m
g 2/
day
AZ
T 3
00 m
g 2/
day
3TC
150
mg
2/da
y3T
C 1
50 m
g 2/
day
NV
P* 2
00 m
g fo
r 13
day
sN
VP*
200
mg
for
13 d
ays
and
afte
r 40
0 m
g/da
yan
d af
ter
400
mg/
day
If C
D4+
<200
or
vira
l loa
d >5
5.00
0se
e st
ages
3-4
At
Chi
ldbi
rth
Con
tinu
e on
goin
g tr
eatm
ent
Con
tinu
e on
goin
g tr
eatm
ent
AZ
T 6
00 m
g +
300
mg
8/da
y3T
C 1
50 m
g 2/
day
NV
P 20
0 m
g fo
r 13
day
san
d af
ter
400
mg/
day
Post
nat
alC
hild
: Nev
irap
ine
Chi
ld: N
evir
apin
e 2m
g/K
g/da
y C
hild
:2m
g/K
g/da
y w
ithi
n w
ithi
n 48
-72
hour
s of
bir
thN
evir
apin
e 2m
g/K
g/da
y48
-72
hour
s of
bir
thM
othe
r: C
onti
nues
ong
oing
tre
atm
ent
wit
hin
48-7
2 ho
urs
of b
irth
Mot
her:
Con
tinu
es
for
30 d
ays
unti
l lac
tati
on o
nset
M
othe
r: R
ecla
ssif
ied
in o
neon
goin
g tr
eatm
ent
Aft
er, f
ollo
ws
trea
tmen
t pr
otoc
ol
of t
he p
revi
ous
stag
es
§ In
anem
ic p
atie
nts
(Hb<
8) A
ZT
rep
lace
d by
d4T
: 30
mg
2/da
y fo
r bo
dyw
eigh
t le
ss t
han
60 K
g; 4
0mg
2/da
y fo
r bo
dyw
eigh
t ov
er 6
0 K
g. A
ll w
illbe
adv
ised
to
form
ula
feed
*In
case
s of
into
lera
nce
NV
P w
ill b
e re
plac
ed b
y In
dina
vir
or N
elfi
navi
r+W
omen
vis
ited
for
the
fir
st t
ime
at c
hild
birt
h
36
5. Haart treatment in patients with tubercolosis in intensivetreatment
The indication for using the therapy for HIV infection in pa-tients in intensive treatment for tuberculosis regards thosewho have a CD4+ count of less than 200: it is absolute forpatients with less than 50 CD4+ per mm3, and conditionedupon the clinical and immunological situation for those withCD4+ greater than 50 but less than 200.1 When antiretrovi-ral therapy starts being administered to a patient with HIV inintensive treatment for TB, there may be paradoxical reac-tions that fall under the name of immuno-reconstitution.35
Moreover, the many reactions between anti-TB and anti-retroviral drugs are to be taken into consideration if we are toconduct two treatments at the same time.36 Lastly, simultane-ous administration of anti-TB and antiretroviral therapy maycreate confusion in taking the drugs. It is thus often prefer-able to wait for the first two months of anti-TB therapy be-fore starting administration of antiretroviral drugs; however,below 200 CD4+, the infection progresses so rapidly that it isoften fatal to put off therapy. As a rule, patients with lessthan 200 CD4+ must be very closely monitored, especially ifthe decision is made not to start antiretroviral therapy.Otherwise, the course of action would appear to be that ofsubstituting the nevirapine in first line therapy schemes dueto its interferences with rifampicine, a drug almost alwayspresent in anti-TB therapy schemes in African countries. Butthe alternatives involve considerable difficulties, first amongwhich adherence to the therapy, as the number of pills to betaken on a daily basis increases – doubled in the best of cir-cumstances. This is a difficulty that regards one of the mainalternatives ABC1 – whose formulation in a single pill withzidovudine and lamivudine is available only at prices that areat least triple that of the other three-drug formulations in de-veloping nations. A second alternative, efavirenz, raises – ifthis is possible – a greater number of doubts due to the diffi-culty of using it, particularly in the population of women inchildbearing years, given its already mentioned possible ter-atogenetic effects:3 and it should be kept in mind that this
37
type of population represents more than 50% of the HIVpositive persons in developing nations. Lastly, the third rec-ommended alternative – substituting nevirapine withsaquinavir/ritonavir – is impractical due to its scarcity. Onthe other hand, the therapeutic scheme with nevirapine maybe used – albeit with some caution given the approximatelyone-third reduction of the bio-availability of nevirapinewhen administered at the same time as rifampicin.3 Thischoice saves the features of easy administration of the drugformulations with nevirapine and uniformity in treatment,and appears to be the most appropriate when unable to waitfor the conclusion of the intensive phase of TB treatment (thefirst two months). In fact, TB-HIV co-infection has a ratherhigh prevalence in Africa, and the use of rifampicine is con-sequently just as high. Conditioning the use of nevirapinewould require re-examining the first lines of treatment in ahighly significant percentage of therapy-candidate HIV cases,thereby considerably compromising the feasibility of the pro-posed model. The possible availability of other drug combi-nations (in particular that with three NsRTI including aba-cavir) in a single pill at prices comparable to those currentlyin force for other three-drug formulations could offer a use-ful alternative in treating TB-HIV co-infection.
Bibliography1. G Liotta, E Buonomo, G Creton, L Emberti Gialloreti, M Magnano,M.C. Marazzi. A home care program for people living with AIDS inMozambique. XII Int. Conf. on AIDS and STDs in Africa. Ouagadougou,9-13 dec. 2001; Abstract book p.212. L Emberti Gialloreti, L Palombi, G Guidotti, E Buonomo, I Nathave, GLiotta, M.C. Marazzi. Pilot program for prevention and treatment ofAIDS in Mozambique. XII Int. Conf. on AIDS and STDs in Africa. Oua-gadougou, 9-1 dec. 2001; Abstract book p.593. WHO. Scaling up antiretroviral therapy in limited-resource settings.Guidelines for a public health approach. Geneva 20024. Centers for Disease Control and Prevention. 1993 revised classificationsystem for HIV infection and expanded surveillance case definition forAIDS among adolescents and adults. JAMA 1993 Feb 10;269(6):729-305. Yeni PG, Hammer SM, Carpenter CC, Cooper DA, et al. Antiretroviraltreatment for adult HIV infection in 2002: updated recommendations of theInternational AIDS Society-USA Panel. JAMA 2002 Jul 10;288(2):222-35
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6. Holmes CB, Losina E, Walensky RP, Yazdanpanah Y, Freedberg KA.Review of human immunodeficiency virus type 1-related opportunistic in-fections in sub-Saharan Africa. Clin Infect Dis 2003 Mar 1;36(5):652-627. Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med,1997. 126(12): p. 946-9548. Hogg RS, Yip B, Kully C et al. Improved survival in HIV-infected pa-tients after initiation of triple-drug antiretroviral regimens. Cmai 1999:160: 659-659. Montaner JS, Reiss P, Cooper D et al. A randomized double-blind trialcomparing combination of nevirapine, didanosine and zidovudine in HIV-infected patients: the INCAS study. Italy, The Netherlands, Canada andAustralia Study. JAMA 1998; 279:930-710. Stazweski S, Kaiser P, Montaner J et al. Abacavir-lamivudine-zidovu-dine vs indinavir-lamivudine-zidovudine in antiretroviral naïve HIV-in-fected adults: a randomized equivalent trial. JAMA 2001; 285:1155-6311. Stazweski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zi-dovudine and lamivudine, efavirenz plus indinavir and indinavir plus zi-dovudine and lamivudine in the treatment of HIV infection in adults.Study 006 Team. N Engl J Med 1999; 341: 1865-7312. Casado JL, Dronda F, Hertogs K, et al. Efficacy, tolerance and phar-macokinetics of the combination of stavudine, nevirapine, nelfinavir andsaquinavir as salvage regimen after ritonavir or indinavir failure. AIDSRes Hum Retroviruses 2001; 17 :93-9813. Van der Valk M, Kastelein JJ, Murphy RL et al. Nevirapine-contain-ing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001; 15:2407-1414. Bartlett JA, DeMasi R Quinn J, Moxham C, Rousseau F. Overview ofthe effectiveness of triple combination therapy in antiretroviral naïveHIV-1 infected adults15. Food and Drug Administration approved a new, extended release for-mulation of ZERIT. Available on www.aidsinfo.nih.gov16. Sarner L, Fakoya A. Acute onset lactic acidosis and pancreatitis in thethird trimester of pregnancy in HIV-1 positive women taking antiretrovi-ral medication. Sex Trasm Infect 2002; 78:58-917. Kebba A, Atwine D, Mwebaze R, Kityo C, Nakityo R, Peter M. Ther-apeutic responses to AZT + 3TC + EFV in advanced antiretroviral naiveHIV type 1-infected Ugandan patients AIDS Res Hum Retroviruses 2002Nov 1;18(16):1181-7 18. De Truchis P, Force G, Welker Y, Mechali D, Pulik M, Chemlal K,Rouveix E, Devidas A, Praindhui D, Mamet JP; CNAF3008 Group. Effi-cacy and safety of a quadruple combination Combivir + abacavir +efavirenz regimen in antiretroviral treatment-naive HIV-1-infected adults:La Francilienne. J Acquir Immune Defic Syndr 2002 Oct 1;31(2):178-82 19. Emberti Gialloreti L, De Luca A, Perno CF, et al. Increase in surevivalin HIV-1 infected subjects in Matola, Mozambique, after the introduction
39
of Combination therapy with mgeneric manufactured Antiretrovirals:preliminary results from the DREAM cohort. Abstracts of 10th Confer-ence on Retroviruses and Opportunistic infections. Boston, February 10-14, 2003, p122.20. Mock PA, Shaffer N, Bhadrakom C et al. Maternal viral load and tim-ing of mother-to-child- transmission, Bangkok, Thailand. Bangkok Col-laborative Perinatal HIV transmission Study Group. AIDS 1999 Feb 25;13(3): 407-1421. Garcia PM, Kalish LA, Pitt J et al. Maternal levels of plasma humanimmunodeficiency virus type 1 RNA and the risk of perinatal transmis-sion. N Engl J Med 1999; 341: 394-40222. Mofenson LM. Interaction between timing of perinatal Human Im-munoideficiency virus infection and the design of preventive and thera-peutic interventions. Acta Paediatr Suppl 1997; 421:1-923. Hart CE, Lennox JL, Pratt-Palmore M. Correlation of human im-mundeficiency virus type 1 RNA levels in blood and the female genitaltract. J Infect Dis 1999 Apr; 179(4): 871-224. Mofenson LM, Lambert JS, Stiehm ER, et al. Risk Factors for perina-tal transmission of human immunodeficiency virus type 1 in women treat-ed with zidovudine. N Engl J Med. 1999; 341: 385-39325. Fawzi WW, Msamanga GI, Spiegelman D et al. Randomised trial ofeffects of vitamin supplements on pregnancy outcome and T cell counts inHIV-1-infected women in Tanzania. Lancet 1998 May 16;351(9114):1477-82.26. Luzzati R, Del Bravo P, Di Perri G, Luzzani A, Concia E. Riboflavineand severe lactic acidosis. Lancet 1999; 353:901-227. Blanche S, Tardieu M, Rustin P et al. Persistent mitochondrial dys-function and perinatal exposure to antiretroviral nucleoside analogues.Lancet 1999; 354:1084-928. Lipshultz SE, Easley KA, Orav EJ et al. Absence of cardiac toxicity ofzidovudine in infants. Pediatric Pulmonary and Cardiac Complications ofVertically Trasmitted HIV Infection Study Group. N Engl J Med 2000;343:759-6629. Bulterys M, Nesheim S, Abrams EJ et al. Lack of evidence of mito-chondrial dysfunction in the offspring of HIV-Infected women. Retro-spective review of perinatal exposure to antiretroviral drugs in the peri-natal AIDS collaborative Transmission Study. Ann N Y Acad Sci 2000;918:212-2130. Committee APRS. Antiretroviral Pregnancy Registry International In-terim Report for 1 January 1989 through 31 July 2002. Wilmington NC:Registry Project Office31. Hellerstein MK, Wu K, McGrath M, et al. Effects of dietary n-3 fattyacid supplementation in men with weight loss associated with the ac-quired immune deficiency syndrome: Relation to indices of cytokine pro-duction. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Mar1;11(3):258-70.
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32. Shabert JK, Winslow C, Lacey JM, Wilmore DW. Glutamine-antioxi-dant supplementation increases body cell mass in AIDS patients withweight loss: a randomized, double-blind controlled trial. Nutrition. 1999Nov-Dec;15(11-12):860-4.33. Fawzi WW, Mbise RL, Hertzmark E, Fataki MR, Herrera MG, Ndos-si G, Spiegelman D. A randomized trial of vitamin A supplements in rela-tion to mortality among human immunodeficiency virus-infected and un-infected children in Tanzania.Pediatr Infect Dis J. 1999 Feb;18(2):127-33.34. Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJ, Hunter DJ. Ra-tionale and design of the Tanzania Vitamin and HIV Infection Trial. Con-trol Clin Trials. 1999 Feb;20(1):75-90.35. Havlir DV,Barnes PF.Tuberculosis in patients whit human immunode-ficiency virus infection.N Eng J Med.1999;340;367-373. 36. DeSimone J A, Pomerantz R J, Babinchak T J. Inflammatory reactionsin HIV-1-infected persons after initiation of higly active antiretroviral ther-apy. Ann Intern med.2000;133;477-454. For intereactions with cy-tochrome P-450 CYP3A : Buman W J, Gallicano37. K, Peloquin C.Therapeutic implications of drug interactions in thetreatment of human immunideficiency virus-related tuberculosis.Clin In-fect. Dis.1999;28;419-429.
41
Chapter 3
The DREAM program and the struggle against malnutrition
1. Background and justification
Since the early 1980’s, the humanitarian efforts of the Com-munity of Sant’Egidio have been characterised by a constantcommitment to bringing relief to people in critical situationssuch as wars and natural disasters; this commitment has of-ten meant fighting hunger and malnutrition. These effortshave sought to respond quickly to the needs found: human-itarian emergency programs have been carried out, withfood distribution and support for therapeutic and supple-mentary nutritional centers; in other situations, we have in-tervened with agricultural aid programs, distributing seedsand implement kits so that cultivation could be resumed;and lastly, wherever and whenever the country’s internal sit-uation has allowed, we have conducted long-term publichealth programs oriented towards fighting malnutrition andinfectious diseases. The Community of Sant’Egidio viewsthe struggle against malnutrition in the broadest sense: fromprevention to treatment, from controlling protein-energymalnutrition to the more hidden forms of micronutrient de-ficiency. It has always been clear to us that hunger and mal-
42
nutrition must be fought in order to prevent possible epi-demics at critical times.Sant’Egidio’s DREAM program, backed up by these years ofexperience in fighting hunger and malnutrition, now faceswhat may be an even greater, and lesser known, challenge:malnutrition coupled with HIV/AIDS infection. At the heartof this challenge lies the knowledge that in Sub-SaharanAfrica much of the population is vulnerable to both of theseconditions, and that there exists a synergy between the twothat to date has been little studied but is very dangerous interms of human life and the deterioration of social and com-munity life.
2. Malnutrition, infection, and the HIV/AIDS epidemic
In addition to having some 30 million people living withHIV/AIDS, in Sub-Saharan Africa most of the populationlives under the threat of poverty and food insecurity.
Tab. 1 – Characteristics of vulnerability in some Sub-Saharan Africancountries struck by food shortages and by the HIV/AIDS epidemic(Data source: UNDP/UNAIDS/FAO)
Country % of adults Poverty (% of % Malnourished % ofwith HIV population children (0-5 years population
living on less weight for undernourishedthan $2 a day) age<2 Zscore)
Malawi 15% 76% 25.4 % 33%Zambia 21% 87% 25.0 % 50%Mozambique 13% 78% 27.0 % 63%Tanzania 17% 50% 29.0 % 47%
This shows that a broad segment of the African populationis extremely vulnerable to the independent or synergetic ef-fects of malnutrition and infection with HIV/AIDS.
2. The malnutrition, infection, and HIV/AIDS epi-demic complexIn 1968 the international scientific communityrecognised with reason and clarity the synergetic re-
43
lationship linking nutrition of status to infections,and that nutritional deficiencies, increase the mor-tality, severity and duration of many infectious dis-eases. Therefore public health programs were force-fully directed towards intervening in both direc-tions: correcting states of malnutrition and combat-ing infection.Malnutrition is almost always the result of combina-tion of infectious diseases and dietary deficiencies in-teracting in a mutually reinforcing manner.Malnutrition lowers immune defences and increasesthe risk and severity of infections. While an inade-quate diet may in and of itself cause death and, like-wise, infectious diseases may be lethal regardless ofnutritional status, most frequently the cause ofdeath in poor African countries is due to the inter-action between insufficient food intake and infectivepathology. The infection process exacerbates of nu-trients, loss, because of the host’s metabolic re-sponse and because of the loss of tissue, such as in-testinal tissue. These factors worsen malnutritionand further damage the organism’s defences. Thiscycle is responsible for the high rates of mortalityand morbidity in those African populations heavilyexposed to infectious diseases and food shortages.The complex nature of these interactions makes ittruly difficult to distinguish cause from effect. Thesefacts leads us to reflect on the huge scale of theHIV/AIDS epidemic in Sub-Saharan Africa and,while we know that the poorest and most malnour-ished populations tend to be the hardest hit by HIV,clearly show that malnutrition is one of the decisiverisk factors in the spread of the epidemic.
The vicious circle linking malnutrition, AIDS, immune-systemdeficit and other infectious diseases functions very smoothlyin favourable environments like these fragile African societies,causing millions of deaths each year.
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Figure 1. The vicious circle linking HIV/AIDS, malnutrition, other infections and immune-system deficit demonstrates the powerfulinteraction of the three variables. (Source: WR Beisel 1996)
This shows that:• HIV begins the circle by weakening the immune system• Immune deficiency leads to an increase in infectious dis-
eases, which worsen malnutrition.• Malnutrition leads to a greater deficit of the immune sys-
tem, whose weakness worsens the effects of the HIV infec-tion.
• The cycle speeds up the progress of infection from HIV toAIDS.
3. DREAM’s objectives for combating malnutrition
As a public health program, DREAM’s priority is to inter-rupt the vicious circle linking HIV/AIDS infection to the im-mune system and to malnutrition. For DREAM, it is essential to slow down this vicious circleby combating malnutrition, so as to maintain good nutri-tional status in at-risk populations or in those already livingwith HIV/AIDS.Obviously good nutrition does not cure AIDS, but it is a ba-sic aid that complements HAART: it will help to maintainand improve health status of those living with HIV/AIDS by
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delaying the progression from HIV to AIDS, fighting oppor-tunistic infections and improving patients’ quality of life.The most frequent result of HIV/AIDS infection is weightloss, a major reduction in muscular tissue, and the conse-quent shortening of patient survival. The scale of this weightloss is dramatic: a person afflicted by HIV/AIDS may lose upto 30-50% of his body mass before succumbing to the dis-ease. One of the most common and feared manifestations ofthe disease is Wasting Syndrome; its clinical signs are pro-found involountary weight loss >10% of baseline bodyweight plus either chronic diarrhea (at least two loose stoolsper day for >30 days) fever, and marked weakness (≤30 days,intermittent or constent). This syndrome, which was includ-ed in the list of AIDS-associated pathologies in 1987, disfig-ures the patient’s body, reduces his functional capacity andprevents even a minimal social life, and, above all, increasesthe risk of death. In Africa, Wasting Syndrome was recog-nised early on, and infection with HIV/AIDS quickly came tobe known as “slim disease.” It is well known that the leadingcause of weight loss in people with HIV is insufficient food:diet is often hypocaloric and hypoproteic in the face of in-creased metabolic requirements due to the infection.
The energy and protein needs of people with HIV/AIDSare increased.HIV infection increases the energy requirement:it is recommended that an HIV+ adult increase hiscaloric intake by 10-15%.An additional 400 calories per day need to be provid-ed for men, and 300 calories per day for women.
HIV infection increases protein requirements:it is recommended that an HIV+ adult increase hisprotein intake by 50-100%.It is necessary to go from a recommended protein in-take of 0.8-1.0 g/kg of body weight for the healthypopulation to 1.2-2.0 g/kg of body weight.For a 70kg adult, this translates into a daily protein in-take of between 84 and 140 grams. This broad range
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of recommended protein intake obviously depends onthe patient’s ability to consume a diet with such a highprotein level. (Source: Woods 1999)
The disease’s progression is also associated with shortages ofmicronutrients such as vitamin A and zinc. Increased re-quirements for vitamins A, C, E and B6, selenium and zinchave been found in persons afflicted with HIV/AIDS. Studiesare still under way to establish adequate intake levels forthese and other micronutrients, but a diet that increases pa-tients’ daily intake has been recommended for some timenow. It has been confirmed that a vitamin A deficiency in-creases mother-to-child transmission, whilst other studies arenecessary to understand the role of other micronutrients or ofmultiple nutritional deficits in mother-to-child transmission.In conclusion, there is clearly room in the treatment and pre-vention of HIV/AIDS for nutritional therapy, and the DREAMprogram has included this in its own prevention and therapymeasures as an integral part of its approach.
In keeping with FAO’s recommendation included in the nu-tritional support manual for people with HIV/AIDS, the ob-jectives of this nutritional therapy are to be found in the fol-lowing points:
• Maintaining body weight and physical strength• Improving nutritional status with recovery of weight lost
during infective episodes• Ensuring adequate levels of intake for each nutrient, in
particular vitamins and other micronutrients that have animpact on the immune system
• Improving and maintaining immune system functions• Delaying the transition from HIV to AIDS• Improving response to drug treatments• Proper dietetic management of symptoms associated with
the disease, such as: anorexia, digestive problems and poorabsorption
• Maintaining the work capacity, physical performance andindependence of those living with HIV/AIDS
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4. DREAM’s approach to nutritional support for people withHIV/AIDS
Education to promote an healthy and balanced nutrition
Every DREAM service features times and places devoted tohealth education, especially education that promotes awholesome and balanced diet; the educators, who aretrained periodically, possess a unique tool for working effec-tively: the book “How’s Your Health”.This book enables even those who cannot read to learn howto manage their own health and diet. The sessions are heldon various occasions, at the day hospital, at the Mother &Child center (also for learning and consolidating basic nutri-tional information for children), and sometimes even in pa-tients’ homes, involving the family and neighbours. Everymeeting with the patient can be an opportunity to convey in-formation and advice on how to improve diet and food hy-giene. Who handles dietary education? All of DREAM’s op-erators are trained in this area, but promoting proper diet ismainly the job of the activists. Some activists are people withHIV/AIDS, DREAM patients, who have tested the pro-gram’s efficacy and work within it to help others. Their pres-ence has a positive influence on others and encourages thosewho have trouble regaining their hope and will in combatingthe disease.Certain topics, such as checking for symptoms such as diar-rhoea, nausea, anorexia and vomiting due to the disease ortreatment are dealt with by the physicians and nurses.
Assessment and monitoring of nutritional status
DREAM offers a simple assessment that provides dietary,anthropometric, clinical and laboratory information. Nutritional case history and clinical exam: the doctor con-ducts a detailed survey of the patient’s dietary history andevaluates the quality and quantity of the diet, trying to iden-tify any mistakes, shortages and needs for education and as-sistance. During the clinical exam, the doctor looks for signs
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and symptoms such as: anorexia, nausea, vomiting, diar-rhoea, steatorrhea, dysphagia, etc. Anthropometric parameters: Taking the weight and heightand calculating the BMI are basic elements that are checkedperiodically so that they can be monitored constantly. Mea-suring the arm circumference and the tricipital skinfold sup-plements the basic parameters for better assessment of bodycomposition.Special attention is paid to the correct measurement of theseparameters, with periodic calibration of the instruments.For children, the anthropometric assessment is done accord-ing to UNICEF’s instructions, particularly in the first twoyears, by calculating the weight by age in relation to theNCHS/WHO reference values, monitoring growth using thegrowth curve.Biochemical parameters: The laboratory provides routineindications with regard to albuminaemia, revealing theseverity of protein-energy malnutrition; the results of the he-mochrome make it possible to evaluate the anaemia. Specif-ic parameters are required for more in-depth assessments,especially those involving interactions between metabolismand HAART therapy.Computer support: An essential element of DREAM. It helpsthe physician in assessing and monitoring nutritional statusby complementing the reading of the anthropometric datawith the other clinical and nutritional parameters, allowingthe viewing of the anthropometric indicators chosen in rela-tion to the cutoff points identified for the screening of indi-viduals at high risk for malnutrition.At the end of this assessment process, the physician assigns anutritional regime to the patient to optimise his diet and nu-tritional status.
Food aid to people with HIV/AIDS and their families.
DREAM has chosen to donate food to people withHIV/AIDS and their families in order to ensure food securi-ty and contribute to a wholesome and balanced diet.Based on the assessment of his nutritional status and his so-
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cial and family needs, every DREAM patient is included inthe program of food assistance for himself and his family.
The means chosen by DREAM to improve the diet of thosewith HIV/AIDS and their families are:
1. Monthly food deliveries in the form of dry rations tobe taken home.
2. Distribution of small meals during day hospitals andvisits to Maternity.
3. Delivery of meals and nutritional supplements inHospital for hospitalised patients.
The DREAM program has chosen to donate foods that arepart of the local diet and that complete their nutritional re-quirements.
Tab. 2 – Foods most commonly distributed to families by DREAM.
Grain Legumes and nuts Flour mixes and fortified oils
Rice Peas Corn Soy BlendCorn and Corn flour Lentils Wheat Soy BlendCookies Beans Soybean oil
Peanuts
The amount distributed is calculated on the family’s size, eco-nomic conditions, and the number of people with HIV/AIDSand their health status.Each distribution is accompanied by correct information onthe nutritional characteristics and the best means of conserv-ing and cooking each foodstuff distributed. The DREAMstaff is responsible for giving recipes and advice for improv-ing the flavour and maintaining the nutritional qualities ofthe food. Finally, the staff regularly samples the opinions andideas of the beneficiaries regarding the acceptability and ap-proval of the foods distributed.
The food storage-transport-distribution chainProper health and hygiene management of the foodstorage-transport-distribution chain is a basic requi-
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site for DREAM. Special care is taken to ensure prop-er conservation of the foodstuffs; the warehouse andthe premises where the foods are prepared and distrib-uted must be suitable and secure to prevent any sort ofdamage to these commodities. The foods distributedmust all be high in nutritional quality, and their sourcemust be such as to guarantee the wholesomeness andsafety of the product, based on international food hy-giene and safety standards.
Supplementation with vitamins and other micronutrients,nutritional counselling
The physician is responsible for prescribing and controllingsupplements of vitamins and other micronutrients. There-fore every supplement is administered free of charge and un-der the physician’s control, for a period of time that is limit-ed to actual requirements and in any case until the body’sneed has been replenished.The physician is also responsible for the nutritional coun-selling that is intended to lead to proper management of nu-tritional symptoms and signs, such as anorexia, diarrhoea,nausea and vomiting, stomatitis and dysphagia, dryness ofthe mouth, constipation, etc., caused either by the disease oras adverse and side effects of the HAART therapy and/orother therapies. The meeting with the patient is also aimedat intervening in a specific nutritional and therapeutic situa-tion, to avoid those foods that interfere with the therapy andto increase the consumption of foods or of vitamins andminerals depleted by the drug therapies.
BibliographyR. Gibson. Principles of Nutritional Assessment. Oxford University Press1990N.S. Scrimshaw, C.E.Taylor & J.E. Gordon. Interaction of Nutrition andinfection. Monograph. Ser. W.H.O. 57:3-329. 1968WR Beisel. Nutrition and Immune Function: Overview. J. Nutri-tion.126:2611S-2615,1996
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WHO Technical Report Series 854. Physical Status: the use and the inter-pretation on anthropometry. Geneva 1994N. Graham. Epidemiology of the Wasting Syndrome in HIV/AIDS. Nutri-tional Aspects of HIV infection. Arnold press. London. pp 1-17, 1999Serwadda D., Mugerwa RD, Sewankambo N.K at al. Slim Disease: a newdisease in Uganda and its associations with HRLV-III infection. Lancet,2,848-852,1985Center for Diseases Control. Revision of the CDC surveillance case defi-nition for the Acquired immunodeficiency Syndrome. MMWR; 36 (Suppl2S): 3S-15S 1987FAO. Series 29. Human Nutrition in Developing World. Rome 1997FAO,WHO Living well with HIV/AIDS. A manual on nutritional careand support for people living with HIV/AIDS. Rome 2002FANTA PROJECT. HIV/AIDS: a guide for nutrition, care and support.Food and Nutrition Technical Assistance Project, Academy for Educa-tional Development. Washington DC, 2001N.Woods. Dietary Recommendations for HIV/AIDS Patient. NutritionalAspects of HIV infection. Arnold press. London. pp 199-211, 1999T.Castleman, E.Seumo, B.Cogill .Food and Nutrition Implications of An-tiretroviral Therapy in Resource Limited Settings (Draft). FANTA PRO-JECT. 2003WHO. Scaling up antiretroviral therapy in resource-limited settings:Guidelines for a public health approach. 2002.
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Chapter 4
Organization of services
1. Home care
Home care is for patients whose clinical conditions do notlet them have access to outpatient and day hospital services:it is a service for those patients who are clinically and so-cially the weakest, and it expresses the choice of guarantee-ing care for all. In developing countries, reaching healthcarecenters is even more difficult for those patients with neitherthe energy nor the resources to do so on their own. Besidesdifficulties in transportation and structural shortcomings ofpublic services inadequately sized in proportion to realneeds as a consequence of insufficient resources, an often de-termining factor of poor compliance is the condition of eco-nomic and general weakness of many inhabitants. This serv-ice thus provides the concrete possibility of bringing careeven where it would never get, ensures all patients of theirright to health, makes it possible to conquer the isolation towhich so many are relegated, rebuilds a network of person-al relationships, and involves families in the care and recov-ery processes.
OrganizationThe home care service headquarters is part of the day hospi-tal structure; in fact, a close relationship between these twoservices is necessary to facilitate the patient’s transfer fromone mode of assistance to another. In its first months of ac-tivity, DREAM saw a rapid shift of patients from home as-sistance to day hospital – a first step forward made possiblefor many by improved clinical conditions, recovered inde-pendence of movement, and the renewed hope for life.
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The assistance teamThe team consists of Mozambican social workers and health-care personnel and a coordinator. Everyone is required to have,and is furnished with, specific training in home care for personswith AIDS. The service receives consulting services from aphysician for diagnostic and therapeutic aspects in patient care.
AccessThe home care service is for patients residing in an area nearits headquarters. Patients are indicated by families, hospitalfacilities, healthcare centers, and service personnel present inthe territory.
ServicesThe services respond to the needs emerging from a multi-di-mensional evaluation taking into consideration the economicand social conditions of the patient’s family, as well as his orher clinical conditions and residual functional capacities. Thisservice was structured taking into account the drama thatmany families experience with one or more ill persons. Re-duced economic resources; malnutrition; inability to maintainordinary household hygiene; failure to make civil registrationentries; dropping out of school; and the inability to accesseven basic care: the accumulation of these circumstances is of-ten a fact from the outset, and home care is associated with in-terventions aimed at seeking an environmental sustainabilityindispensable for improving life conditions and for the thera-py to work.The services contemplated by the program are as follows:– assessment evaluation of the social situation;– assessment of the health situation;– home care (cleaning the home, preparing meals, disinfect-
ing water, providing a water filter);– social support for keeping minors in school, cutting through
red tape, seeing to legal matters, running the household;– transporting the patient to healthcare facilities for medical
consultations and diagnostic exams;– health education and counseling to the patient and his or
her family;
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– improving the quantity and quality of the nutrition of thepatient and his or her family;
– personal care and hygiene services;– home nursing;– medical consultation; – supply of antiretroviral and basic drugs.
Modes of operation1. During the first home visit, the patient’s case history isgathered, an initial clinical evaluation made, and nutrition-al, social, and living conditions assessed. At that time, analy-ses, counseling, the doctor’s visit, and other clinical checksare planned.
2. During the weekly meeting of the social/healthcare team,an overall evaluation of each patient is made to define thenumber of weekly visits by personnel and the type of activi-ties to be carried out.
3. Each social/healthcare worker going to the patient’s homereports the visit in the social section of the patient’s file, no-tifies the physician of any changes in the state of health, andreports to the service coordinator any changes in social andliving conditions.
The DREAM program places great importance on the rela-tionship established between workers and patients. Trainingcourses stress that maximum respect is required when enter-ing the patients’ homes with the delicate task of caring for themany aspects described above. Courtesy, privacy, and discre-tion in proposing solutions and interventions are essential forrespecting the dignity of all and for the program to succeed.
2. Day hospital
Day hospital is for patients that are HIV positive or with full-blown AIDS. The population accessing the service is com-posed of both children and adults.
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OrganizationThe service headquarters has:a) a patient’s waiting area, with chairs and benches to en-
sure comfort;b) a room near the entrance for reception, with a computer
to gather data;c) a room for medical examinations;d) a counseling room;e) a room for tests and samples to be taken;f) a pharmacy area;g) a warehouse storing foods for nutritional support;h) a meeting area, or a multifunctional room that can be set
up as a meeting room.
The assistance teamThe day hospital is manned by healthcare and social workers(physicians, nurses, social workers). Operators receive ongo-ing training and are coordinated by a management team chiefwho, as already pointed out, has specific highly professionalfeatures gained in Europe and refined on site, is strongly inte-grated with all team members. A group meeting is held once aweek to discuss clinical cases and problems related to the serv-ice.
AccessPatients access DH on their own or as indicated by physi-cians from health care service. An objective of the DREAMprogram is to foster care for entire households.
The pathThe path begins with reception/waiting in an area for this pur-pose, which may be a yard or room. During the wait, the dayhospital’s social workers concentrate on creating a cordial, re-laxed atmosphere: patients are offered soft drinks and freshwater, there is conversation, and a collective reading of thebook “Como vai a saúde” (Guerini e Associati Editore-Milan-1999) – The Community of Sant’Egidio’s basic health educa-tion course – is proposed, to introduce the concepts that willbecome necessary.
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The patient then accesses the reception room – an initial en-try at which operators gather personal data and open theclinical file. Special attention is given to translation: manypersons need the mediation of operators for local languages.Once the clinical file is opened, a nurse proposes HIV testing tothe patient (pre-test counseling) in the room for this purpose.Those who test negative are invited to counseling and in-formed as to how the illness is transmitted and the rules forprevention. Those testing positive are invited to counselingand, once informed of their state of health, to take part in theDREAM program. They are given a card, which they are toldto keep with care, with their ID code (univocal identificationnumber) and the center’s telephone numbers that may be calledfor any problem.After informed consent, the patient gives samples for initialanalyses, and the service coordinator schedules the firstmedical examination.Based on the results of the lab tests and the clinical examina-tion, the physician chooses the therapeutic path in accor-dance with the DREAM protocols. Simplifying communica-tion and procedures is a decisive element for the whole inter-vention to be effective. As already seen, language problems,reading difficulties or illiteracy, and lack of experience withwritten instructions and taking note of what must be done,can – without paying specific attention to how to transmit in-formation – become insurmountable obstacles. This is why,to simplify subsequent visits, patients are given cards of a dif-ferent colour for each type of appointment (red for testing,yellow for nutritional support, green for the medical exami-nation, and blue for medication). This is how the patient ac-cesses the center for testing, medical examinations, pickingup medication, and nutritional support Additional attention is devoted to distributing the therapy.Each patient receives the medication in named envelopes indi-cating, even by symbols (the sun for the morning, the moonfor the evening), when it is to be taken. At that time, the pa-tient is given a small plastic package, hermetically sealed forproper conservation.The clinical file is computerized.
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PrivacyAlthough operating in situations of health emergency,the diagnosis and treatment centers and the labs thattake part in the DREAM program are required to de-vote special attention to safeguarding privacy.*At diagnosis and treatment centers, tests and coun-seling are carried out by healthcare workers bound byprofessional secrecy. The clinical file is designed toguarantee separate access for healthcare personneland social/assistance workers: data on HIV positivityand the stage of the illness thus remain confidential.To improve compliance (adherence to the diagnostic-therapeutic program), the patient is required to au-thorize home visits or the use of his or her phonenumber if he or she misses the appointments set bythe center.*Upon reception, the analysis labs assign to the sam-ples an identification code, thereby preventing treat-ment of personal data and the possible consequentspread of private information.*Data are computerized, gathered, and sent to the cen-tralized archive for the remote medicine service solelyby ID codes. The computerization program scramblesthe patient’s data automatically, thereby ensuring max-imum confidentiality while permitting the transmissionof information useful for improving diagnosis and carefrom one end of the world to the other.
3. The mother/child healthcare center: preventing verticaltransmission
This service is performed at the maternity wards located atthe healthcare centers. Its purpose is to test pregnant women,prevent mother-to-child transmission, and care for mothersin accordance with the pre-established protocols (see chap.2).All women going to the healthcare centers when pregnant areinformed as to the existence of the DREAM program.
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OrganizationThe mother/child healthcare center has a minimal structureas well, corresponding to the functional requirements:a) a waiting area, suitably equipped, with seats and benches;b) a room for HIV testing and for counseling;c) a room for taking samples;d) a room for the medical examination and delivering med-ication;e) a pharmacy.
The assistance teamAs with the other services, the assistance team consists ofphysicians, nurses, and social workers. The presence of anurse and a physician with pediatric qualifications is recom-mended.
AccessPregnant women going for prenatal checkups at the health-care center are informed as to the possibility of accessing theservice: schedules, characteristics, and the fact that it is freeof charge.
The pathA qualified nurse performs pre-test counseling, in which thewoman is informed as to how the illness is transmitted, par-ticularly from mother to child, and is made aware of the ex-istence of the DREAM program, and above all of the possi-bility – and benefit – of being able to receive all the necessarycare in the event she is HIV positive.Those who wish to do so are tested for HIV. In this popula-tion group, DREAM has recorded 100% compliance – aconfirmation of the effectiveness of the communication,combined with the actual possibility of therapeutic supportin case of need. This particularly encouraging fact has fewprecedents or similar events in other African experiences.Women with positive test results are sent to counseling, in-formed of their health status, and invited to take part in theDREAM program, which allows them to be treated with an-tiretroviral drugs and to prevent transmission to their child.
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Women deciding to take part in DREAM give a sample andundergo a medical examination.The physician chooses the therapeutic path in accordancewith the protocols predefined based on the clinical and labresults.From the moment of entry into the program, for the follow-ing months of the pregnancy, the woman is followed con-stantly until childbirth. She accesses the service for medicalexaminations and samples; she can pick up medication andreceive health education for artificial feeding; nutritionalsupport is available.After childbirth, the service covers both mother and child.
ComplianceFor a long time, adherence to therapy has been one ofthe main obstacles to introducing antiretroviral thera-py in limited resource countries. DREAM’s experiencepoints out an effective, viable way towards overcomingthe stumbling block of adherence to therapies and alle-viating these concerns. During its first months of life,DREAM has recorded very high compliance. These en-couraging results are no accident. They are rooted inthe careful communication of positive messages.1. Being HIV positive is not a death sentence: duringtesting and counseling, each patient is explained thatthe drugs available today allow effective care guaran-teeing a good standard of living. Thanks to the thera-py, being HIV positive is no death sentence.2. DREAM guarantees therapy to all those that needit, free of charge. 3. No patients are left on their own, but are accompa-nied on their clinical and diagnostic itinerary: they re-ceive explanations as to the type of analyses to be per-formed and how they are important for identifying themost effective therapy; therapy is simplified as muchas possible to guide them in taking their medicationregularly; patients are invited to contact the center forany problem that may arise, by phone if they can, orin person.
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4. The guarantee of privacy, the respect that surroundseach person, the courtesy and availability of opera-tors, and introduction into a pleasant, welcoming en-vironment: these are all factors that contribute to thechoice of coming back.5. The rediscovered hope for life, the rapid improve-ment of clinical conditions, and the possibility formany to return to a normal social and working life:these all key factors for the entire environment inwhich the patient lives, and are the best guarantee ofadherence to prevention programs.
Caring for pregnant womenDREAM privileges pregnant women and the moth-er/child pair: this is the choice for Africa’s future.Women are encouraged to be tested with the securitythat they will receive care for themselves and the hopethat they will bear healthy children free of HIV.Nutritional support is essential for facing the delicategestation period, and is often an aid for sustaining theother children.Throughout pregnancy, each contact with the center isan occasion for getting advice, support, encourage-ment, and friendship, for women in a difficult periodin their lives, and at times without support from men(deceased, away working, etc).We take particular care in explaining to the futuremothers the need for artificial feeding: short health ed-ucation courses are effective and useful to gain famil-iarity with water filters, bottles, and dosages of pow-dered milk.While waiting, and with the help of the center’s staff,fears and confusion can be overcome by meeting oth-er women going through the same experience and see-ing them feed artificially.When childbirth is near, each woman receives an im-portant basic kit: water filter, bottle, and powderedmilk, along with an information sheet using drawingsand simple graphics to depict the procedures to be fol-
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lowed. This is no minor safety device for the program:some women may be unable to reach the center fortheir childbirth and must be ready to put what theyhave learnt into practice, to keep their healthy babyHIV free.All the same, each women knows that it is importantto reach the center within three days after childbirth,for the child to receive the specific therapy, plus all thecare he or she might need.The first arrival of the new mother and her newbornat the DREAM center stresses the new birth and thevictory over the virus by appropriate means (party,gifts), which help strengthen the bonds that are deci-sive for the entire duration of the treatment.
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Chapter 5
The molecular biology laboratory for antiretroviral treatment
in Africa
1. Introduction
The DREAM program for treating AIDS in developing coun-tries places particular importance on diagnosis – understoodboth as level I diagnostics and as such advanced diagnosticsas, for example, quantifying the viral load and evaluating theCD4+ lymphocyte sub population.Although leukocyte immuno-phenotyping in monitoringHIV in the West has been routine for years, in Africa this pos-sibility, within the context of the services performed by thenational health systems, is quite limited – if not absent alto-gether – in the vast majority of countries. But having a reli-able CD4+ count of the patient’s blood is at present an indis-pensable factor in the administration of antiretroviral thera-py. In addition to the physician’s strictly clinical observations,the exact clinical picture of a patient with HIV is also madeup of analysis results, which must be solid and reliable.Methods of molecular biology measuring viral DNA orRNA also make it possible to effectively monitor the thera-py in subjects treated with drugs inhibiting virus replication.This is why the DREAM program includes a molecular biol-ogy lab as a specific support to the HIV diagnosis and careservice.The lab exams deemed necessary for these purposes arethose that make it possible to monitor the therapy and therelated toxic effects that it may have, and see to perfecting
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and using a variety of analytical techniques with differinglevels of complexity and specialization.The first level involves the careful determination of thehaemochrome and of the complete leucocyte formula. Thisexam is crucial for the utility of the final report, given HIV’scharacteristic of specifically attacking and killing CD4+lymphocytes, and in monitoring the toxic effects of drugsbeing used for the first time, such as zidovudine.The second level corresponds to the need to monitor thestate of kidney and liver functions and to measure the con-centration of specific ions such as Fe++.The third level involves the double platform instrumentcount of the lymphocyte sub populations, specifically CD4+and CD8+, an essential support for monitoring antiretrovi-ral therapy and the patient’s state of health.The fourth level of specialization consists in applying the an-alytical methods needed to quantify the plasma viral load –a parameter that is an indicator of the state of infection and,along with the CD4+ count, one of the major parameters forevaluating the therapy to be administered.
The classification that is made cannot ignore other lab prac-tices which, although they cannot be catalogued in terms ofspecialization and complexity, make real contributions tomaking the lab’s service a sound one. These are:1. the possibility of carrying out rapid tests on HIV positivi-ty on whole blood, plasma, or serum;2. the possibility of producing analytical grade distilled wa-ter for the dilutions and preparations envisaged by the vari-ous diagnostic kits used;3. the use of an effective sterilization and waste eliminationsystem;4. keeping the proper temperature of reactives and samplesof whole blood, plasma, or serum, also for establishing aserum bank;5. developing and implementing a proprietary software pro-gram for managing the exams.Separate thought must be given to instrument mainte-nance. In a limited resource country, the introduction of a
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molecular biology lab often raises for the first time theproblem of maintenance of sophisticated lab equipment.Specific training must thus be planned for local mainte-nance personnel, to ensure over time the indispensabletechnical assistance. At the same time, lab workers mustacquire a minimum technical ability in order to carry outat least basic instrument maintenance, to allow a certaindegree of laboratory self-sufficiency when intervention bythe maintenance technician cannot be guaranteed quicklyand in every circumstance.
2. The facility
The use of advanced methods poses problems as to the ade-quacy of the facility in which to house the laboratory.In this regard, the minimum requirements necessary for thepremises of the labs are listed below, taking into accountthat facilities of this kind may be installed at medium-largecenters.
Condition of the premisesThe areas must guarantee the possibility of suitably deploy-ing the various moments of analysis. In particular, theremust be a room for reception and reporting, also to be usedas an office/archive. There must also be a confined area inwhich to treat infected waste with an autoclave. It will benecessary to have a warehouse area, or at least to keep thesurplus material in boxes and cartons in a place where sam-ples are not processed. Virology areas must be large enoughto permit the unidirectional flow of the sample, in order toprevent contamination.Lighting surfaces must not permit opening to the outside.Windows, if any, are to be sealed and provided with curtainsin a washable, non-absorbent material (plastic is ideal).It is important that the flooring be in a washable, non-porous material (e.g. linoleum treated with waxing prod-ucts). Walls and casings shall, where possible, be treatedwith washable paints.
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Work stations surfaces shall be washable and acid resistant.All areas shall be air conditioned. The size of the air condi-tioning system in the area where the cytofluorimeter and the–80°C freezer are to be deployed shall take into account theheat produced by the machines.It should be ensured that the electrical system has an earth-ing system; otherwise, a grounding cable should be provid-ed, since the lab has electrical equipment using water.Constant, continuous electric power is indispensable. Giventhe environmental conditions and the quite possible occur-rence of voltage rushes or temporary absence of power(which may be prolonged), an autonomous electric genera-tor must be provided that can intervene automatically, evenat night, given that some of the methods require overnightincubation and the freezers for conservation at –80°C can-not maintain such low temperatures for long; samples andexpensive reactives would risk being made unusable. Thefreezer must be connected to the general electric board di-rectly, to keep the motor’s absorption from interfering withthe remaining equipment. Current stabilizers for the moresophisticated equipment – such as the cytometer, which usesa laser source – are useful.
3. Analysis parameters
It should be kept in mind that the laboratory is exclusivelyfor monitoring antiretroviral therapy. Therefore, althoughscreening tests may occasionally be performed, this is not itsspecific function. The use of rapid HIV testing frees the labfrom such practices as ELISA or the Western Blot, which aremore burdensome in terms of time, cost, and necessary ma-nipulation. In fact, the rapid tests completely free the labworker, since they may be carried out anywhere so long asthe minimum requirements necessary to effectively safe-guard the worker are kept in mind. A kit can be equippedwith single-use lancets (needles are not recommended), cot-ton wool, disinfectant, and disposable gloves, and can beused to perform the test anywhere. The screening tests
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adopted in the program have thus been chosen bearing inmind their use chiefly at the diagnosis and care centers,thereby providing the possibility of organizing work in or-der to be able to carry out the HIV testing and the counsel-ing on the same day, sending the specialized lab only thesamples from positive patients. The essential parameters to be determined are as follows:1. Hemochrome and complete leucocyte formula2. Liver function3. Kidney function4. Iron5. CD4+ and CD8+, percentage and absolute levels6. Viral load as level of plasma RNA
Analytical determinationsHAEMATOLOGY
The erythrocyte and leucocyte count is to be performed withautomatic equipment permitting the two cellular types to becounted separately. Leucocytes are counted after the ery-throcytes are lysed. The equipment must also be able tocount in a differentiated fashion, both as a percentage and inabsolute values, the leucocyte sub-populations and theplatelets. It is good to have printed reports available forevery determination.The equipment needed to count the lymphocyte sub-popula-tions is the flow cytometer, or cytofluorimeter. From thestandpoint of determining for diagnostic purposes the CD4+and CD8+ lymphocytes, the type of cytofluorimeter mostwidely used in the West is with blue laser, perhaps associat-ed with an optional red laser. This is the only kind of ma-chine that enables routine, accurate, and realistic – albeitsurely not the most affordable – determination of lympho-cyte sub-populations. Other machines on the market try toavoid the considerable costs of purchasing a blue laser cyto-fluorimeter to the detriment of the number of determinableparameters. For example, using green or red lasers makes itpossible to reduce costs considerably, but with the loss of theability to use a series of fluorochromes that are importantfor internal controls and for the overall evaluation of the ac-
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quisition. Another market tendency is to reduce the fluidsand optics, making these cytofluorimeters virtually trans-portable. But these machines’ fluid ducts clog more easilyand the flow is more unstable than in a fixed machine.Moreover, instability problems are found in the light sourcedue to the difficulty in controlling the cytofluorimeter’s in-ternal temperature. This is why, to equip a reference labora-tory, an argon laser, cytometer, one of the standards in theWest, has been chosen. The system also has a carousel mech-anism making it possible to automate the operations for in-serting the test tubes containing the blood to be tested,thereby diminishing manipulation of the sample. Lastly, thecytofluorimeter communicates with a computer that sets upits activities and stores the results obtained, thereby obtain-ing an important database at the same time.The absolute CD4+ and CD8+ count is made in double plat-form. Samples are processed by the lyse non-wash method,using a generic lysant and reduced volumes of antibody.
BIOCHEMISTRY
These determinations are made using colorimetric methodsand require a spectrophotometer. Instrumentation with in-terchangeable filters permitting the selection of three or fourwavelengths – those needed for the colorimetric determina-tion of the most frequently required parameters – is suffi-cient. The following are usually measured:1. transaminases2. albumin3. amylases4. direct and total bilirubin5. creatinine6. iron.It is important for the photometer to have a multiple or sin-gle self-sampling system, to eliminate the risk deriving to theoperator from movement of the cuvette in the system’s hous-ing. The photometer should also have a data entry and/orstorage system; display only machines should be avoided.Micro-methods have been perfected to enable the use of re-duced volumes of reagents and serum. The micro-methods
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were validated in-house and are periodically verified. Theacceptability of the method is subordinated to a value r>0.9of the regression lines.
Development of methods for biochemistryThe clinical biochemistry performed in the lab useswell-known, trialled diagnosis kits. These are colori-metric kits developed in such a way as to simplify theiruse as much as possible. The samples are normally pre-pared in accordance with standardized protocols thatinvolve using automatic pipettes with fixed volumes of100, 250, 500, and 1000 µl. This solution is certainlyuseful where a photometer is used requiring cuvetteswith a volume of 3 ml, or where it is impossible to workaccurately with reduced and variable volumes. However, methods employing smaller volumes (mi-cro-methods) are more convenient. By evaluating thecell’s useful volume, micro-methods may be developedthat, by using volumes tailored to the machine, con-siderably reduce the fixed cost of the reagents neededfor each determination. The other advantage found isthe possibility of reducing sample volumes, particular-ly in pediatrics and neonatology, where large quanti-ties of venous blood are hard to draw.This is made possible by a complete serious of auto-matic micro-pipettes, and above all by the technicalknow-how of lab workers perfectly capable of work-ing with micro-volumes on a routine basis.Other advantages are the reduction of infected materi-al to be eliminated, and less manipulation of the sam-ple by the lab worker.
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VIRAL LOAD
The plasma’s viral RNA is measured by bDNA (branchedDNA). This method has the advantage of being based onamplifying the signal and not the target as with the methodsusing PCR (polymerase chain reaction), and therefore of be-ing less susceptible to the problem of contamination. Cur-rently, the bDNA system appears to be the one that offersgreater coverage for the various extant HIV subtypes. Fur-thermore, bDNA is not subject to the errors typical of thePCR procedures (amplification of contaminant RNA, muta-tions induced by the polymerase). This results in a reducedlevel of sterility necessary for the analyses to be performed.The method is relatively easy to perform, although it in-volves the use of micro-volumes and requires two workingdays, with rigid timing for carrying out the various steps.The method’s disadvantages certainly lie in the extremelyhigh cost for the kit, plus the fact that single samples cannotbe processed (to optimize the kit’s use, many samples mustbe processed at the same time, and the response awaited atthe clinic). Furthermore, the bDNA technique is influencedby the instability of the reagents, and particularly of the con-trol RNAs that are employed to determine the standardcurve from which to obtain the viral load of the samples inquestion. The luminescent substrata used by the detectionsystem are also extremely light sensitive and to be kept care-fully. Experiments are currently under way to research andvalidate alternative, less expensive systems to quantify theviral load using the dosage of viral antigens.
4. Work flow
Blood is normally transported the same morning to the lab-oratory in slightly refrigerated insulated containers.
Receiving specimensSpecimens must always be sent together with a form contain-ing at least the case clinical history record number, name ofthe patient, provenance, signature of the director of the
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Health Center, number of vials collected from each patient.The Reception office will check that the number of vials cor-responds to the amount declared and that they are all labeled.
Using the appropriate laboratory software a progressivenumber will be assigned to each specimen and this numbermust be attached to the specimen and written on the accom-panying form. Thus the specimen will be unequivocallyidentified throughout its life in the laboratory and will guar-antee the patient’s privacy.The aliquots are normally two vacutainers: one with a violetcap containing K(3)EDTA, for haematology and evaluationof plasma RNA and one with a red cap without anticoagu-lants for biochemical analysis.
Distant CentersWhen specimens come from centers which are very farfrom the reference laboratory (several hours of driv-ing), some precautions must be taken to ensure thequality of analysis.If CD4+ cell counts need to be assessed it is importantto find out if there is an automatic blood cell counter inthe center where the specimen was collected. If so it isbetter for the center to carry out the Complete BloodCount (CBC) analysis itself and either email the reportor, time allowing, attach it to the aliquot to be sent tothe reference laboratory. If CBC is routinely performedby microscopy it is better to send this aliquot too to thereference laboratory. In fact although in order to assessCBC, specimens should be processed within a fewhours from collection, automatic counting makes itpossible to evaluate a much greater population andthus compensates underestimation due to delay inanalysis. If this option is preferred, attention should bepaid to haemolysis. In fact if only the aliquot for CD4+analysis is sent, haemolysis is a minor problem (thespecimen is lysed to allow the reading of the differentlymphocyte sub-populations); if both aliquots are sentgreater care should be taken in transport. Vials should
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be placed in insulated containers in appropriate vialracks possibly placed on material which will absorbshocks (polystyrene, foam rubber).
Sorting the aliquotsSEROLOGY
Vials for serological analysis are processed using normal cen-trifuges. Centrifugation must be carried out immediately. The following analyses must be performed the same day:AlbuminCreatinineThe following analyses can be carried out the morning after:Bilirubin TotalBilirubin DirectGOTGPTIron
Specimens to be processed the following day must be storedat +4C°.
HEMATOLOGY
One of the 2 aliquots with the anticoagulant will be used forthe Complete Blood Count. Then, if necessary, an aliquot willbe processed for Flow Cytometry. Flow Cytometry analysismay be performed even the day after blood collection. In thiscase the aliquot with whole blood and EDTA will be stored ina dark place at room temperature. The following day analysiswill be performed according to the protocol.
VIROLOGY
The second aliquot with anticoagulant will be centrifugatedin order to separate the plasma necessary to determine the vi-ral load. All the plasma will be kept in the freezer at –80 C°.A list of samples present in the freezer is to be kept and prop-erly updated.
ReportsThe results of the different tests will be recorded electronically
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the day after, at the latest. The report will be printed and deliv-ered only when all the requested analyses have been performed.Only the results of viral load determination may be given at alater date and should be printed on labels with patient identifi-er and result. Reports shall be folded and stapled and filed inappropriate folders, one for each center of provenance.
5. Waste disposal
Waste disposal is a public health issue. Contaminated mate-rial may be burnt but one should make sure that all the ma-terial has actually been destroyed. Alternatively, where thereis no efficient sterilization and waste disposal system, an au-toclave set according to international standards, i.e. at least15 minutes at 120 degrees centigrade and saturated with va-por may be used. Treatment is confirmed by adhesive tapecontaining a substance which changes color with heat.Waste thus treated may be disposed of together with non-in-fectious material. Fluids (supernatant, excess sera) are col-lected in rigid plastic containers with 100/200 ml of 5%bleach solution (sodium hypochlorite), left overnight andlater disposed of.
6. Safety
In each laboratory safety measures should be implementedto protect personnel. The main rules regarding laboratorypractice, specimen handling and use of equipment should bestressed.
Safety RulesGeneral rules– It is forbidden to eat or drink in the laboratory andto store food or drinks in refrigerators where labora-tory products are stored.– Personnel must wear laboratory coats to be takenoff before leaving.
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– Access to laboratory premises is forbidden to unau-thorized personnel. Suppliers and agents must be received at the receptionor in the chief’s office.– Never use glassware which is cracked and/or splin-tered. Never wash or reuse microscopy slides. Neverwash and reuse disposables.– When blood specimens are handled, personnel mustuse disposable gloves to be removed and thrown awayeach time processing is interrupted, no matter the rea-son. Personnel who are last to leave the laboratory inthe evening must check that everything is in proper or-der and that equipment has been turned off.
Precautions when using electrical equipment– Immediately report any malfunction of equipment,presence of worn out wires, damaged plugs or sockets. – Equipment run electrically should not be placednear explosive or inflammable material.
Precautions when processing biological materialsInfectious agents may be parasites, helmynths, fungi,bacteria and viruses. Therefore all biological materialprocessed and not only that coming from positive pa-tients should be treated as infectious.An efficient disinfectant should be present in eachroom. A dispenser of a 5% bleach solution (sodiumhypochlorite) is useful.– Never pipette by mouth.– Hands must be washed before leaving the laboratory.
Precautions when using Ultraviolet Rays– Avoid direct exposure to UV rays.
Rules for use of centrifugesPersonnel who use centrifuges must know exactlyhow they work and are run. In particular before use:– Check that all centrifuges have safety devices whichdo not allow them to start with the lid open.
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– Observe recommended maximum speed and sampledensity ratings.– Check that containers are accurately balanced.Moreover:– clean centrifuges and rotors after use so that theymay be used later without risk;– immediately switch off a centrifuge that vibrates orproduces strange sounds.
7. Quality control of the diagnosis circuit
An effective quality control for such a complex procedure asdetermining diagnostic parameters involves establishingrules for each individual step. That is to say that it is neces-sary to analyze and validate the whole diagnostic circuitprocess and not merely one aspect of it. Towards these ends,key steps for a blood sample’s entire path have been as-sessed, from withdrawal to reporting, to transport and ef-fective use in instrument methods, thus highlighting opera-tive moments requiring validation.No kind of quality control may be considered apart from arepresentative sample, both in terms of number and qualityof the population to be investigated, and only thus yieldinga statistically meaningful result.
PROCESS PHASES RESPONSABILITY• Sampling diagnosis and care center• Forming aliquots diagnosis and care center• Conserving and transporting
aliquots diagnosis and care center• Conservation at lab laboratory• Analytical determination laboratory• Reporting laboratory
Sampling:Sampling is performed using exclusively vacutainers – theonly containers capable of ensuring the conditions of safetyand sterility necessary for carrying out analyses of this kind.
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The vacutainers are filled to capacity. Smaller volumes mayinfluence the analytical result.
Preparation of aliquots:Aliquoting blood specimens must take into account thespontaneous precipitation of haematic cells; vials must al-ways be kept gently agitating to avoid clotting (coagula-tion). Only vials containing (K3) EDTA should be used. Ifclotting (coagulation) occurs, the specimen cannot beprocessed. Even micro-coagulation due to incomplete or in-sufficient mixing of blood and anticoagulant may influencetest results.
Storage and transport of aliquots:Blood should not be exposed to heat shock but must bestored at room temperature to avoid haemolysis or loss ofrepresentativeness of the white cell component. Blood mustbe sent to the test center as soon as possible within accept-ance time set by the laboratory
Storage of specimens in the laboratory:Specimens must be accepted when they are delivered. Speci-mens, which have not been registered, cannot be stored in thelaboratory. Storage of specimens to be used for the differenttests shall follow the laboratory workflow. Vials should alwaysbe hermetically sealed and stored at room temperature forhematology, at + 4°C for serology and at -80°C for virology.
Tests:HAEMATOLOGY
Complete Blood Count is carried out with an automaticblood cell counter. Instrument performance is checked dailyusing a standard synthetic serum and plotting a graph withdeviations from the standard.The percentage of lymphocyte sub-populations is assessedusing a flow cytometer with an argon laser (488 nm), indouble platform by the “lyse non-wash” method. This en-sures that error in reproducibility is not greater than 15%.Frequency of quality control depends on the amount of tests
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performed. The laboratory is part of an external quality con-trol circuit.
BLOOD CHEMISTRY
Clinical biochemistry is performed by spectrophotometerusing diagnostic kits to which reductions in volume are ap-plied. Periodically, control normal and pathological sera aretested in every determinable parameter.
ReportsResults are recorded on a master program for laboratorymanagement. The program handles a data bank containingall results generated in the laboratory thus allowing a com-parison with previous results from the same patient. More-over the program permits differential printing of parameterswhose results and subsequent reports are generated at dif-ferent times. It also allows to check printed reports or thoseundergoing validation and indicates date of print
BIBLIOGRAPHY
Spandrio L., “Biochimica Clinica”, ed. Sorbona, Milano giugno 1989Wilson K., Walzer J., “Metodologia Biochimica”, Raffaello Cortina Edi-tore, Milano 2001UNAIDS Technical Update, HIV Testing Methods, November 1977World Health Organization: Global programe on AIDS, Manual for na-tional AIDS control programs, August 1989Sherman GG, Galpin JS, Patel JM, Mendelow BV, Glencross DK., “CD4+T cell enumeration in HIV infection with limited resources.” J ImmunolMethods. 1999 Jan 1;222(1-2): 209-17Diagbouga S, Durand G, Sanou PT, Dahourou H, Ledru E, “Evaluationof a quantitative determination of CD4+ and CD8 molecules as an alter-native to CD4+ and CD8+ T lymphocyte counts in Africans.” Trop MedInt Health. 1999 Feb;4(2): 79-84Jani IV, Janossy G, Brown DW, Mandy F., “Multiplexed immunoassaysby flow cytometry for diagnosis and surveillance of infectious diseases inresource-poor settings.” Lancet Infect Dis. 2002 Apr;2(4): 243-50Rabkin M, El-Sadr W, Katzenstein DA, Mukherjee J, Masur H, MugyenyiP, Munderi P, Darbyshire J., “Antiretroviral treatment in resource-poor set-tings: clinical research priorities.” Lancet. 2002 Nov 9;360(9344): 1503-5T. Elbeik, et al., “Quantitative and Cost Comparison of Ultra-sensitive HumanImmunodeficiency Virus Type 1 RNA Viral Load Assays: Bayer bDNA Quan-tiplex Versions 3.0 and 2.0 and Roche PCR Amplicor Monitor Version 1.5”Journal of Clinical Microbiology March 2000, p. 1113-1120, Vol 38, No.3.
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Chapter 6
Computerization, remoteconsultation, remote validation
1. Introduction
In order to manage and monitor patients correctly, softwarehas been developed to enable real-time analysis of each per-son’s clinical situation.This software is in fact not a mere archive, but a workingtool used whenever the patient reaches one of the diagnosisand care centers. “DREAM_prg” this is the name of theprogram - manages not only the clinical and chemical por-tion with detailed medical logs, but also each contact the pa-tient has with the various services.Each patient is automatically assigned an ID (univocal iden-tification number), identifying him or her in all subsequentaccesses and becoming his or her reference and file number.The identification number is an alphanumerical code withtwo letters indicating the care center of reference followedby 6 digits. The identification number of children born with-in the MCPC vertical prevention scheme will be the same asthat of the mother, with the code “P1” added.At each medical examination, all the clinical annotations areentered directly into the computer. For each new access, alog is created indicating each patient’s symptoms, diagnosis,and therapy. Each symptom and diagnosis is followed by anotes space where the physician can freely write any anno-tations. The program can show the type of antiretroviraltherapy and separate it from the remaining therapeutictreatment. After each medical examination, a new log isprinted and inserted in the clinical file.
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Laboratory exam reports reach our care centers in hardcopy and by such computerized means as e-mail, diskettes,or digital pens. DREAM_prg therefore stores all the haema-tochemical examinations undergone by the patients, in or-der to easily monitor biohumoral variations over time. Witheach arriving report, an updated report is printed summariz-ing all the laboratory levels, and added to the file.A portion of the program also manages such social interven-tions as distributing water filters and delivering mosquitonetting. From time to time, DREAM_prg will indicate theneed to replace water filters.
2. Mother/child monitoring
DREAM_prg also has a section dedicated to monitoring theprevention of mother-to-child HIV infection. When a preg-nant woman’s week of gestation is entered, the due date isautomatically indicated, and will be indicated again as theevent approaches.This feature allows us to forecast the number of child-births in a given period, thereby facilitating the prompt ad-ministration of Nevirapine by the time the newborns are72 hours old. This session will also report peri-partum in-formation (type of childbirth, APGAR, etc). Each newbornwill thus have a neonatological, and subsequently a pedi-atric log.Dream also has a graphic portion displaying the growthcurve in percentiles, in order to follow growth deficits –and if necessary correct them with drugs and/or nutrition-al support.Although from the clinical standpoint, artificial or breastfeeding regards the newborn exclusively, it is a datum al-ways reported, of course, by the mother during the exami-nation. DREAM_prg sees that this datum, when reported onthe mother’s log, will also be available in the newborn’s, andthe other way around. This simple feature makes it possiblenot to lose indispensable information on the mother-to-childprevention program.
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3. Agendas
All appointments for samples, medication, medical examina-tions, or for other purposes are made by information technology.In fact, DREAM_prg has electronic agendas that plan the vari-ous accesses and automatically signal each day’s appointments. Thus appointments are computerized for medical examina-tions, for giving samples, for delivering medication, and forproviding nutritional support. A special agenda is devotedto urgent checks; it is used when a patient has not come tothe center and must be tracked down, with the grounds forhis or her absence checked.DREAM_prg is therefore a tool capable of monitoring eachpatient’s adherence to the care program and promptly indi-cating those who, for a number of reasons, have failed toshow up on the appointed days.
4. Remote medicine, remote consultation
The remote medication service makes it possible to provide re-mote consultation for special clinical cases; simply by supply-ing the patient’s ID code, it is in practice possible to remotelyconsult the entire clinical file in Jpeg format. Remote consulta-tion is currently active with physicians from a number of cen-ters of reference. DREAM_prg thus enables us to remotelymonitor the clinical conditions of all our patients. Moreover,being able to remotely obtain an updated version of all the da-ta allows us to promptly identify any errors in data entry, or tosee which patients have failed to show up for their appoint-ments. This kind of control is performed on a weekly basis.The data are completely separated from the program, and thismakes it possible to download updates of DREAM_prg fromthe Internet without interfering with the data bank at all.
5. Technical features
At the larger care centers, the program is on line over local
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networks, thereby making it possible to access all the datafrom a number of PCs: one for the physician, one for thenurses, one for the coordinator and social workers.In this way, the passage of clinical data, drug prescriptions,and the planning of interventions is made on line, therebycutting down paperwork and reducing the possibility forerror.The data files are backed up on a daily basis, whether or notthe operators give the command. Thus this backup creates 7security files a week, thereby guaranteeing 7 copies of up-dated data at all times. Once a week, each center’s PC server will automatically e-mailto a local server a scrambled and anonymous copy of eachcare center’s archive. The program deletes the personal data ofthe patients, who will be identifiable only by their ID code.This local server will gather the archives from all the carecenters, which may be consulted or sent to the Comunità’sphysicians.A high-speed Internet connection is not required to performthis remote medicine service. A 33 Kbyte/sec modem con-nection is sufficient. These technical features make the mod-el reproducible even in those areas without high-speed lines,where only a phone line is available.Training courses for using the program have been devel-oped, attended by physicians, nurses, and social workers.DREAM_prg is easy to use, and will soon be available invarious languages that the operator may select when startingthe program.
6. DREAM-laboratory
Computerizing the molecular biology labThe computerization of the molecular biology lab is bymeans of a database that interacts with hematology, spec-trophotometry, cytofluorimetry, and branched Dna.The program uses modern control systems to manage the re-porting of the analytical parameters, thereby eliminating theerror percentage typical of manual reporting.
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This software controls the reception, processing, and report-ing of each blood sample.Reporting is dual: hard copy and in electronic format, throughinterfacing, via Internet or using simple floppy disks, with theDREAM_prg program. The analytical data will thus be auto-matically downloaded into the program, thereby erasing onceagain any manual reporting errors.Internet reporting is protected by password and, in any event,as discussed in the observations on privacy, contains no pa-tient personal data, but only the univocal identification code.Telematic reporting allows centers distant from the lab to re-ceive results, thereby limiting transport problems only to thedelivery of the blood samples.In reporting the results, a remote validation has been created.Criteria have been established by which some parametersmay require outside validation. For this purpose some dedi-cated software packages, such as those managing the cytoflu-orimeter or the bDNA, can be used off line by European pro-fessionals remotely validating and reporting the acquisitiondata. This mechanism, the only one of its kind, makes con-tinuous supervision possible, particularly of the parametersmost important for monitoring the therapy.
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Chapter 7
Costs and facilities
1. Personnel
DREAM includes the participation of both local and non-local personnel.
Non-local personnelA feature of the Community of Sant’Egidio’s programs indeveloping countries is that non-local personnel, as volun-teers, are unpaid. Constant presence in the country is guar-anteed by a regular system of shifts. Workers – for the mostpart healthcare personnel (physicians with various special-ties, university researchers, biologists, nurses, and rehabili-tation therapists) – are from a number of countries. Thereare also social workers and other professional figures withadministrative and logistical supervision tasks, as well aspeople of good will, who are as useful as all the others.Again on a voluntary basis, members of the Community ofSant’Egidio are helped by medical and lab personnel fromvarious European scientific and healthcare institutions.
Local personnelLocal personnel is employed in the medical/healthcare, social,and administrative area, or with logistical support responsi-bilities. Salary levels correspond with the standards of otherinternational agencies present in the country. Healthcare andsocial personnel are trained before hiring and, on a regular ba-sis, are brought up to date at specific training seminars.
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2. Costs
The laboratoryAs discussed above, to prepare a lab capable of effectivelymonitoring antiretroviral therapy and its possible toxic ef-fects, a suitable facility is needed. The following is a list of thevarious items that are the essential units for setting up thelaboratory, with a general indication of the costs, to whichwill be added any costs for restructuring the premises.I. FurnishingsII. Machinery for basic diagnosisIII. Machinery for advanced diagnosis
The total estimated cost for equipping a molecular biologylab is now equal to US$ 330,000.The relatively high initial cost is justified by the need to pur-chase machinery that ensures solidity and reproducibility of re-sults over time. Cost reduction is to be sought in the ordinarymanagement of the reagents, by developing, for example, de-vices aimed at using the volumes that are actually needed, andmethods making it possible to reduce operating expenses.The analytical costs for monitoring a patient based on theclinical/diagnostic protocols used by the DREAM program(cf. Annex II) were calculated. A laboratory out-of-pocketcosts estimate is equal to about US$ 170 per year for pa-tients in antiretroviral therapy, and US$ 95 per year forHIV positive patients not in antiretroviral therapy. Thesecosts may be attributed mainly to determining the viral loadand the CD4+, whose reagents are still excessively expen-sive. As regards the mother-child pair, the average cost forcarrying out the necessary analyses during the first year, ac-cording to the protocols used (see Annex III), is about US$400. In subsequent years it comes to US$ 200 per year.
Cost of antiretroviral drugsAt present, the yearly cost of antiretroviral drugs per personis about US$ 330. The introduction of medications not in-cluded in the two first-choice schemes results in a highercost, which in any event comes to an average of US$ 350.
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Total costsTo the personnel, lab, and antiretroviral drug costs are to beadded the costs for non-antiretroviral drugs, single-use ma-terial, artificial milk, nutritional support, water filters,transport, computerization, and the expenses for the equip-ment and for operating the various facilities. However, thesecosts do not exceed 30% of the total budget and will tend todiminish considering the processes of the economy of scalethat will occur as the various activities are developed.
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Annex II
Protocol for antiretroviral treatmentfor HIV infected people
First Contact. Rapid test for HIV infection (pre-test counsel-ing) is offered to the patient eventually followed by a confir-matory test. Post-test counseling is offered the same day andresults of exam are given to patient.If the exam is negative, the patient record is filed.If the exam is positive, blood specimen is collected from the pa-tient and tested for: CBC, glucose, serum BUN, serum creati-nine, transaminases, proteins and protein electrophoresis,Iron, CD4+ and viral load. Medical follow-up will be arrangedfor the week after: exam results will be given then.
First Medical Examination: patient’s clinical history is as-sessed, and beginning of antiretroviral treatment is evaluat-ed on the basis of the following criteria:
a) if CD4+ are less than 200 or symptoms related to HIV-in-fection are present (WHO Clinical staging: stages 3,4) treat-ment shall begin;b) if there are no symptoms and CD4+ are more than 200but less than 350 wait for results of viral load: if viral load isgreater than 55.000 copies/ml begin treatment. Otherwise,wait one month and then repeat CD4+ and Complete BloodCount. If CD4+ numbers fall begin antiretroviral treatment.If they remain stable or increase the person should be en-rolled for regular follow-up every three months;c) if CD4+ are greater than 350 and there are no symptoms of
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disease, irrespective of viral load, an appointment will bearranged for three months later (CD4+ and CBC check andmedical examination). If CD4+ have remained above 350, pa-tient will be enrolled in a follow-up program every six months.d) if CD4+ are greater than 500, irrespective of viral load,the patient will be enrolled in a follow-up program every sixmonths (see above).
If treatment must be startedTreatment regimens: First Choice:a) Duovir (AZT 300 mg + 3TC 150 mg) 1 pill for two perday + NVP 200 mg 1 pill per day for 15 days. Then two pillsa day for NVP, too (Duovir-N 1 pill for two per day)b) D4t 30 mg + 3TC 150 mg (if body weight over 60 kg useD4t 40 mg) + NVP 200 mg 1 pill per day for 15 days. Thentwo pills per day for NVP, too (Triomune 1 pill per day)If allergic or adverse reactions arise replacement of AZTwith D4t or NVP with IDV should be evaluatedc) prophylaxis with cotrimoxazole if CD4+ count is lowerthan 200/mm3.Supply drugs for a week
Control schedule during treatmentAfter 1 week; CBC. If, at the moment of drawing blood, thepatient has some kind of difficulty or shows for the first timesymptoms such as diarrhea, fever, vomit, rash or other hemust be examined by a doctor. Supply drugs for a weekAfter 2 weeks: Routine medical examination and CBCSupply drugs for a weekAfter 3 weeks:Routine medical examinationSupply drugs for a weekAfter 4 weeks:CBC and transaminasesSupply drugs for a weekAfter 5 weeks:
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medical examination and arrange for next follow up. If thepatient is feeling well:Supply drugs for two weeks If the patient is not feeling well, frequency and type of ex-amination must be decided case by caseAfter 7 weeks:supply drugs for three weeksAfter 9 weeks:CBC and transaminasesAfter 10 weeks:medical examinationSupply drugs for three weeksAfter 13 weeks:Supply drugs for three weeksCBC, transaminases, CD4+After 14 weeks:medical check upAfter 16 weeks:supply drugs for 4 weeksAfter 20 weeks:supply drugs for 4 weeksAfter 24 weeks:collect blood specimen for CBC, serum BUN, glucose, serumcreatinine, transaminases, iron, proteins and protein elec-trophoresis, CD4+ and viral load.supply drugs for 4 weeksAfter 25 weeks:medical examinationAfter 28 weeksmedical examination, result of test for viral load, assessmentof clinical conditions.Supply drugs for 4 weeks
If the patient is feeling well, CD4+ count is over 350, viralload is undetectable or below 10.000 copies/ml in those pa-tients who had 500.000 copies/ml at the beginning of treat-ment, check-up may take place after 6 months but drugs formore than 4 weeks should not be supplied so that the patientis obliged to come back and have his conditions checked.
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Follow-up every Three or Six Months
1st appointment: collection of blood specimen for CD4+ andCBC (once a year, besides CD4+ and CBC, also transaminas-es and viral load); 2nd appointment: medical examination and review of results ac-cording to which beginning of treatment may be decided or not.
Whether or not undergoing treatment, each contact the pa-tient has with the center (blood collection or to get drugs) isan opportunity for the DREAM operators (nurses and socialcare personnel) to assess his/her conditions. If the patient pres-ents new or serious clinical symptoms, he/she must be sent tothe doctor for an examination even if not scheduled accordingto the protocol.
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Annex III
Protocol for antiretroviral treatmentto prevent mother to child
transmission of HIV and to cure mother and child
Pregnancy
First contact:Pre-test counseling, HIV testIf test is negative provide only post-test counseling If test is positive:1) post test counseling2) blood specimen will be collected from the patient to assess:CD4+, Viral load, Complete Blood Count, Serum Creatinine,Glucose, GOT, GPT, Albumin, Iron, Bilirubin Total andBilirubin Direct3) medical examination, counseling for treatment and labor, Antiretroviral treatment shall begin immediately for– all women at week 25 or more of pregnancy– women between week 14 and 25 of pregnancy at WHOclinical stages 3,4)Antiretroviral treatment shall not begin before the end ofweek 144) supply tin of formula and sealed baby’s bottle and water filter5) supply nutritional support6) lesson in health education (description of the program, in-structions on formula feeding, use and management of baby’sbottle which must remain sealed until birth, instructions onthe use of water filter and information on the risks linked touse of unfiltered water. The educator may add other subjects).7) For women who begin treatment:
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– Supply treatment for 15 days– Arrange appointment for the week after for the first con-trol blood specimen– Arrange appointment for 15 days later for medical exami-nation and supply of treatment8) For women before week 25 of pregnancy who do notmeet criteria for initiation of treatment, arrange appoint-ment for 3 weeks later for results of analysis and to assessthe beginnings of antiretroviral theraphy.
For women before week 25 of pregnancy who at first con-tact do not meet criteria for initiation of treatment arrangefor three weeks later:Medical check-up to assess results of analysis:Women with less than 200 CD4+ and/or viral load greaterthan 55.000 copies/ml shall immediately begin treatment.For the others an appointment shall be arranged at week 25of pregnancy to start antiretroviral treatment
After beginning of antiretroviral treatment
After 1 weekCollect blood specimen for CBC
After 2 weeksMedical examinationSupply treatment for 2 weeksSupply nutritional support if necessaryArrange appointment for a week later for collection ofbloodArrange appointment for 2 weeks later for medical exami-nation and supply of treatment
After 3 weeksCollection of blood specimen for CBC, GOT, e GPT. For women who began treatment from week 32 onwards ofpregnancy (because they arrived for their first check at thismoment of pregnancy) blood shall be collected also for CD4+count and viral load
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After 4 weeksMedical examination. If all is well:supply nutritional support Arrange appointment for 2 weeks later to supply treatmentArrange appointment for 4 weeks later for collection ofblood specimen Arrange appointment for 5 weeks later for medical examination
After 6 weeksSupply treatment for 3 weeksSupply nutritional support
After 8 weeksCollection of blood specimen for CD4+, Viral Load, CBC,GOT, GPTSupply nutritional support
After 9 weeksMedical examinationSupply treatment for 4 weeks (if patient has demonstratedgood adherence to control and treatment protocols, other-wise supply treatment for 2 weeks and arrange another ap-pointment)Arrange appointment for 4 weeks later for check up with thedoctor
Post-Partum.
At DeliveryAdministration of nevirapine to child (2 mg/kg)Fill in Child’s case historySupply milk for two weeks and one bottle of mineral waterNew instructions on use of milk and baby’s bottle. Instruc-tions on how to control and inhibit lactation onsetSupply treatment for 2 weeksArrange appointment for 2 weeks later for infant and moth-er for medical examination. Clinical assessment must bemore frequent in low-weight newborns.
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After 2 weeksMedical examination Check weight and clinical conditions of infantSupply treatment for 2 weeksSupply milk for 2 weeksSupply nutritional support Arrange appointment for 2 weeks later for medical exami-nation and collection of blood specimen.
After 4 weeksCollection of blood specimen from mother for CD4+ count,viral load, CBC, GOT and GPTCollection of blood specimen from infant for viral loadCheck weight and clinical conditions of infantMedical examination to decide whether or not treatment ofmother should be continued1) Mothers with CD4+ >350 and with no symptoms at be-ginning of treatment may interrupt ARV treatment if they nomore have milk 2) Mothers with CD4+ between 200 and 350 and viral loadbelow 55.000 copies/ml and with no symptoms of diseasebefore beginning treatment may interrupt treatment, if theyno more have milk 3) All the others shall continue ARV treatmentSupply treatment for 3 weeks (to those who continue)Supply milk for 3 weeksSupply nutritional support if necessaryArrange appointment for 3 weeks later for medical exami-nationArrange appointment for 3 weeks later to supply milk.
After 7 weeks.Check weight and clinical conditions of infant Medical examination, results of blood test for infant, checkconditions of mother and child. If infant has been infected,collect blood specimen for CD4+ count, CBC and bloodchemistry. If infant has been infected arrange appointmentfor medical examination 21 days later to assess test resultsfor infant
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Supply treatment for 3 weeks (if mother is continuing treatment)Supply milk for 3 weeksSupply nutritional support Arrange appointment with mother to collect blood 3 weekslaterArrange appointment with mother 3 weeks later to supplymilk and eventual treatment Arrange appointment with mother for 12 weeks later formedical examination (results of tests at 12 weeks).
After 10 weeksCheck weight and clinical conditions of infant Medical examination if infant has been infected (results ofblood test for infant), evaluate and plan eventual ARV Collect blood specimen from mother (CD4+, CBC, GOT,GPT)Supply treatment for 2 weeks (if mother is continuing treat-ment) Supply milk for 2 weeksSupply nutritional support Arrange appointment for 2 weeks later for medical exami-nation for mother and child.
After 12 weeksCheck up for mother (test results) and childCheck weight and clinical conditions of infant Supply treatment for one month to mother (if under treatment)Supply milk for 4 weeksSupply nutritional supportArrange appointment with mother for 4 weeks later to sup-ply milk and treatmentArrange appointment for 4 weeks later for child if infected.
After 16 weeksMedical examination of child (if infected)Check child’s weightSupply milk and treatment for mother for 4 weeks (if under-going treatment).Supply nutritional support
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Arrange appointment for 4 weeks later to supply milk andtreatment
After 20 weeksMedical examination of child (if infected)Check child’s weight and clinical conditionsSupply milk and treatment for 4 weeks to mother (if ontreatment)Supply nutritional supportArrange appointment for 4 weeks later: – to supply milk and treatment – to collect blood specimen from mother and child (if infected)– for medical examination.
After 24 weeksCollect blood specimen from mother (CD4+, Viral Load,Blood chemistry, CBC)Collect blood specimen from child (Viral Load) and CD4+,blood chemistry, CBC if child has been infected Medical examination for both mother and childSupply milk (type 2) and treatment to mother (if undergoingtreatment) for 4 weeksSupply nutritional supportArrange appointment for 4 weeks later to supply milk andtreatmentBegin weaning the child
Arrange appointments once every 4 weeks to supply treat-ment, milk and nutritional support and to follow up wean-ing until child is 18 months old (check weight and clinicalconditions of child).
CD4+, CBC and blood chemistry checks each six months formother (if no problems have arisen in the meantime).
Check viral load of mother 12 months after childbirth.
Tests for infected children at 9, 12 ,18 months (CD4+ and CBC)Viral Load at 12 months.
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Contents
10 Why DREAM?
17 DREAM: the program
24 DREAM: protocols for diagnosis and treatment
41 The DREAM program and the struggle against malnutrition
53 Organization of services
63 The molecular biology laboratory for antiretroviral treatment in Africa
80 Computerization, remote consultation, remote validation
86 Costs and facilities
90 Annex I – Case history record
98 Annex II – Protocol for antiretroviral treatment for HIV infected people
102 Annex III – Protocol for antiretroviral treatment to prevent mother to child transmission of HIV and to cure mother and child
Printed in Italy on December 2003