Progress Towards 3 x 5Uganda 2003-2005

Geoffrey Taylor

Division of Infectious Diseases

University of Alberta

DART : triple NRTI ( AZT/3TC/TDF) randomized to lab vs clinical monitoring and to continuous vs interupted therapy

54% <50 copies @ 24 wks

Meta-analysis of ARV programs in RLSL. Ivers, D Kendrick, K DoucetteCID 41:217

3 x 5

Uses a public health service approach

Simplified initial and alternate regimens

Limited laboratory requirements

Strengthening of personnel infrastructure

Move to use of ARV’s earlier in disease continuum

Easier to implement , less monitoring , less toxicity

Source:WHO

Equivalent to a vaccine with 80% protective efficacy

Abstain Be faithful Use Condoms

Update on Epidemiology of HIV in the Rakai CohortDr F Wabwire-Mangen4th National HIV Conference Kampala , March 2005

Open cohort study of HIV epidemiology in Rakai district

Initiated in 1986

Rakai : incidence and mortality Incidence of new

infections unchanged in men/women ages 15-49 between 1994 -2003 (1.2-1.5/100py)

2002-2003:125 incident cases

Mortality HIV(-) 1/100py HIV (+) 11.8 -14.0/py

2002- 2003 : 200 deaths

81% of decline in prevalence from 1994 to 2003 can be accounted for by mortality

What will be the effect of ARV’s on prevalence? ARV’s may increase survival in HIV (+)

populations ie increase duration of disease ARV’s may reduce infectivity Will availability of ARV’s broadly alter risk

behaviours? Wide spread availability of ARV’s may increase

prevalence , even if incidence is unchanged

Antiretroviral therapy for PMTCT( Preventing mother to child transmission)

Nevirapine (42% reduction in transmission)Maternal single dose NVP at onset of labor Infant single dose NVP syrup within 1 week

HAART : as used in developed countries ( 3 drugs from second trimester): >95% reduction in transmission ( to ~1-2%)

Nevirapine Resistance Genotyping Results NVP resistant mutations were detected in

19% of the mothers and 44% of the babies by 6 weeks

Majority of the mothers had K103N mutants while most of the babies had Y181C mutants

In both mothers and infants the resistance faded by 12-18 months

THE REPUBLIC OF UGANDA

National Antiretroviral Treatment and Care Guidelines for Adults and Children

Adaptation by Dr. Hans Spiegel/CNMC/AAACP

Free ARV Sources - Uganda

MOH Global Fund World Bank

Generics : NRTI’s, NNRTI’s ( nevirapine) Limited lab capability ( CD4)

PEPfAR ( President’s Emergency Program for AIDS Relief) FDA approved ( Brand name) : NRTI’s, NNRTI’s, PI’s

Greater lab support ( CD4, some viral load , no resistance testing) Research Trials

DART ~ 2000

Currently ( March 2005), more drug available in stock than requested by clinics

UgandaHIV and ARV situation 2005

1,000,000 HIV (+) 110,000 immediately need ARV’s (WHO estimate 2003)

3 x 5 target 55,000 June 2005 (WHO)

114 clinics prescribing ARV’s ( 2 districts without) 63,896 on ARV’s ; 10,600 free from Ministry

Major clinics JCRC – private ; 12,500 on ARV’s . IDC – Academic Alliance – adult/peds. Mildmay (charitable – pediatric). Mbuya Outreach ( faith based). Employer clinics eg Bell Breweries, Bank of Uganada, Coca-

Cola

Clinical Management of ARV’s – Uganda (urban)

Limited laboratory monitoring Slow to detect failure

Intensive formal counselling Very intensive clinical monitoring – eg

Q2 week – 1 month clinic visits

Clinical Management of ARV’s – Uganda (urban) Clinical staging for the most part but increasing use of

CD4. Usually start ARV’s only with very advanced disease –

more comorbidities , more drug adverse effects First line regimens use NNRTI’s ( nevirapine, efavirenz)

and 3TC Low genetic barrier to resistance

Resistance testing not used clinically (some country level surveillance)

D4T first line NRTI Sensory neuropathy very common Lipoatrophy

Academic Alliance for AIDS Care and Prevention in Africa

Transferred to Makerere Feb 2005

AIDS Training Program AIDS training program

for physicians (1 month)

ID resident training in Utah

Short course (1 week) Nurses and para-medical

staff ( 250 to date)

AIDS Training Program for Physicians 25 students/ 1 month Session /6 sessions/year Highly competitive Clinical/ Didactic; emphasis on ARV use 350 students trained to August 2005 from 10

sub-Saharan countries Post training , return to local clinics where

regarded as local ‘HIV expert’ or take positions as clinical officers in large clinical/research programs

CASE PRESENTATION

HAART CLINIC

NYAKIBALE HOSPITAL

RUKUNGIRI

Presentation ( 2002 )

36 yr old widow History:h/o Cough x 3/12 Fever x 2/12

Social and occupational History

A peasant, being support by her brother ( in Kampala)

for financial & medical support sometimes food.

Too weak to cater for needs for her young children. Small piece of land to cultivate.

Lab findings

CD4 2 cells / mm3 C x R: Cavitations

Fibrosis of lung tissue With bilateral

reticular opacities

Treatment - started on

Anti TB drugs2 months RHEZ 6 months EH

Septrin tabs ARVSCombivir Efavirenz

Patient was discharged after 2 weeks of D.O.T on TB drugs, Septrin prophylaxis, pyridoxin tabs, iron and ARVS

weight gain - 48 kg HB - 10 g/dl Appetite - improved Sputum - no AAFBS seen

Changed ARVS to - Stavudine - Lamivudine - Nevirapine- ( less expensive , compatible with

continuation phase of Tb Rx)

Weight gained to 53 kg But occasionally she could run out of

ARVS and Septrin due to financial constraints and transport problems

On 20/1/04 She had missed 3/12 of drugs and presented

with cough 3/12 fever on & off, weight loss poor appetite for feeds.

Relevant findings:Wasted, weight 41 kg(from 53 kg)Sputum analysis AAFBS + 2 (3 samples)

CD4-175 cells/ mm3 Retreated Tb Enrolled in free ARV program

Comment by G Taylor

CD4 available in remote location Skilled use of Tb Rx and ARV’s Tb relapse despite following national protocol Logistical and financial problems of ARV’s in

remote clinics prior to national program Intermittent ARV’s - may be resistant to

NNRTI’s and/or 3TC

CASE PRESEENTATIONworkers’ treatment centre II

History

Feb. 2004 MF, 38 yo male, lives about 2km from the clinic,

known HIV +ve Came in with h/o cough x 1 mon. had started anti-

TB drugs and Septrin prophylaxis in Jinja hospital 3 wks prior to this visit and reported improvement.h/o marked wt loss, had no other complaints.

FSH:Married,spouse reportedly HIV –ve ; 3 children not yet had HIV test. Had disclosed status to the spouse.

Follow up- visit 2 (mar 2004)

CD4- 64 CBC ( WBC-2.3 HB- 11.3 PLT – 213 ) More Labs- RFTs,LFTs

Treatment prep- individual counseling Started on D4T,3TC,EFV

Follow up cont.

Clinical

Wt

No new OIs Immunological

70 68 65 63 70 75 74 77 80 80 82

Date Feb 04 Aug 04 Feb 05

CD4 Count 64 168 143

Follow up cont.

Adherence

Anti-TB drugs- defaulted and Rx was restarted

Septrin- Good

ARVs- non- adherence( mar-oct 04)

good (oct- march 05)

Nov: switched from D4T,3TC,EFV to TDF,3TC,EFV

Comment by G Taylor

Major role of private sector occupational health clinics

Concerns about adherence ( as in Canada) and management after failed 1st line regimens ( ie PI based regimens)

HISTORY

Mr N B, 7yr old Karamojong from Kotido. Admitted on October 4th 2004

PRESENTING COMPLAINT

Chest Pain Cough Fever Wt loss

Review Of Systems

FSH: He is an orphan, 3rd born of 5 siblings, 4th and 5th are dead. 1st and 2nd are okay and HIV-ve. Mother is peasant who is on TB treatment for the past 5 mths and ARV for 3mths and 3 other widows are okay.

Cont….

P/E : A school going boy ,grossly wasted ,listless and he is moderately pale, febrile T- 38.20 C and has oral thrush

R/S: He is in respiratory distress, RR=46pm, stony dull percussion right infraaxillar and absent breath sounds

Diagnosis

Right Sided Pleural Effusion R/O Pulmonary Tuberculosis Underlying HIV/AIDS

Management Plan

Chest X-rayConfirmed the presence of effusion SputumAAFB +++ Hb 6.2g/dl HIV (+)

Follow Up – 1 Month

Appetite is improving and still has low grade fever

Wt. 15.4 Kg Hb 7.2g/dl Started 3Tc, d4t and efavirenz Gave supplement foods from paediatric

nutritional ward

ISSUES

1. How reliable is Wt and Hb. monitoring in a resource limited environment.

2. Should HIV patients in contact with TB patients be given TB prophylaxis ( not national policy)

3. If nevirapine is to used in the face of TB treatment, under what circumstances and how?

Comment : G Taylor

Repetitive theme of Tb / Advanced HIV Poorer outcomes when HIV treated at advanced

stage Complex drug interactions Suboptimal national Tb protocol Re-infection

3 x 5 – Uganda ,2005A mixed picture Will exceed 3 x 5

target ARV’s now readily

available in country; many clinicians have some experience

Improved CD4 availability

Problems of personnel infrastructure outside main centers

Intensive clinical follow up will be difficult to sustain

Difficult to initiate ARV’s in very advanced patients

Problems with NNRTI based regimens Resistance Difficult to use with Tb drugs Hepatotoxicity