HIV/AIDS in Africa 2012

John A. BartlettKilimanjaro Christian Medical Centre

Duke University Medical Center

Objectives

• To describe current trends in HIV/AIDS epidemiology in SSA

• To describe current prevention efforts in SSA• To describe HIV-related complications in SSA• To describe the current status of antiretroviral

therapy in SSA

A global view of HIV infection33 million people [30–36 million] living with HIV, 2007

Figure 2.7

HIV prevalence in sub-Saharan AfricaHIV prevalence among adults aged 15–49 years old in sub-Saharan Africa, 1990 to 2009.

1990

2002

1996

2009

Source:UNAIDS.

Figure 2.2

Changes in the incidence of HIV infection, 2001 to 2009

To assesschangesinincidence,theestimatednationalincidenceratewascomparedbetween2009and2001.Countries withachange(decreaseorincrease)intheincidencerateof25%ormoreduringthis periodwereidentified. Inmostcases,theassessmentwasbasedonEPP/Spectrum modelling results (1,2). Forselectedcountries,publishedanalysesofcountry-levelincidencewerealsoused.TheEPP/Spectrumcriteriaforincludingcountries inthis analysiswereasfollows. EPPfiles wereavailableandtrends inEPPwerenotderivedfrom workbookprevalenceestimates; prevalence datawereavailableuptoatleast2007; therewereatleastfourtimepoints between2001and2009forwhichprevalencedatawereavailableforconcentratedepidemicsandatleastthreedatapoints inthesameperiodforgeneralizedepidemics;forthemajority ofepidemic curves foragivencountry,EPPdidnotproduceanartificialincreaseinHIVprevalenceinrecentyears duetoscarcity ofprevalencedatapoints;datawererepresentativeofthecountry;theEPP/Spectrum–derivedincidencetrendwas notinconflictwiththetrendincasereports ofnew HIVdiagnoses; andtheEPP/Spectrum–derivedincidencetrendwasnotinconflictwithmodelledincidencetrends derivedfromage-specific prevalenceinnationalsurvey results.

Source:UNAIDS.

Figure 2.5

Global HIV trends, 1990 to 2009

Number of children living with HIV

Number of orphans due to AIDS

Number of people living with HIV

Adult and child deaths due to AIDS

Dotted lines represent ranges, solid lines represent the best estimate.Source:UNAIDS.

Figure 2.8

HIV trends in sub-Saharan Africa

Number of people newly infected with HIV

Adult and child deaths due to AIDS

Number of people living with HIV

Number of children living with HIV

Dotted lines represent ranges, solid lines represent the best estimate.Source:UNAIDS.

Percent of adults (15+) living with HIV who are female, 1990–2007

0

10

20

30

40

50

60

70

Percent female (%)

Sub-Saharan AfricaGLOBALCaribbeanAsiaE Europe & C AsiaLatin America

1990‘91 ‘92 ‘93 ‘94‘95 ‘96 ‘97 ‘98 ‘99 ‘00 ‘01 ‘02 ‘03 ‘04 ‘05 ‘062007Year

5

Prevention

• Testing• Condoms• Circumcision• Pre-exposure prophylaxis (PrEP)• Microbicides• Vaccines

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Percentage of pregnant women in low- and midde-income countries receiving an HIV test, 2004-2007

Condoms have proven efficacy!

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Percentage of women and men aged 15-49 years who had more than one partner in the past 12 months and reported using a condom during their

sexual intercourse in selected countries with repeat demographic and health surveys, 1998-2007

Male circumcision decreases HIV acquisition risk by 60%

Auvert et al PLoS Med 2:e298 2005; Bailey et al The Lancet 369:643 2007; Gray et al The Lancet 369:657 2007

35

3

9

3

56

5

April 2009 – March 2010

2009 – June 2010

September 2009 – June 2010

October 2009 – April 2010

2008 – June 2010

October 2008 – March 2010

September 2009 – May 2010

January – June 20102009

2007 – 2008

May 2009 – April 2010

6 180

91 300(90 000 in Nyanza alone)

350

542

10 000

5 340

4 700

9 90610 0009 179

6 070

BOTSWANA

KENYA

NAMIBIA

RWANDA

SWAZILAND

UGANDA

UNITED REPUBLIC OF TANZANIA

ZAMBIA

ZIMBABWE

Number of sitesestablished

Time periodNumber circumcised

Table 3.2

Scaling up male circumcisionRecent roll-out of the scaling up of adult male circumcision in nine countries.

Source: Meeting reports and presentations. Durham, NC, Clearinghouse on Male Circumcision for HIV Prevention, 2010.

Tenofovir 1% Gel Microbicide Decreases HIV Acquisition by 39%

Abdool Karim et al Science 2010; 329:1168

Heterologous HIV Vaccine Reduces Risk by 30%

Rerks-Ngarm et al. NEJM 2009; 361:2209

Pre-exposure Prophylaxis

Status of PrEP Studies• iPrEx- FTC/TDF decreased risk of HIV acquisition among

MSM (Grant et al NEJM 2010; 363:2587)• FEM-PrEP- no protective effect of FTC/TDF among

heterosexual women (http://www.fhi.org/en/Research/Projects/FEM-PrEP/htm )

• TDF2- 63% reduction in HIV acquisition among heterosexual men and women in Botswana receiving FTC/TDF (Thigpen et al; Abstract WELBC01 IAS Meeting 2011)

• Partners PrEP- both TDF alone and FTC/TDF reduce risk of HIV acquisition among heterosexual couples (Baeten et al; Abstract MOAX0106 IAS Meeting 2011)

HPTN 052*

• 1763 HIV-1 serodiscordant couples• Seropositive partner had CD4 350-550• Randomized to early or delayed ART (confirmed

CD4<250, or clinical event)• Ascertained whether transmission events linked

through pol gene sequences• Study stopped by DSMB after median 1.7 years; 90%

of couples still in follow-up

*Cohen at al NEJM 2011 365:493

HPTN 052 Results*

• 39 transmission events overall; 4 in early therapy group (0.3/100 person years) vs. 35 in delayed therapy group (2.2/100 person years), HR=0.11, (p<0.001, 95% CI 0.04-0.32)

• 28 linked transmission events; 1 in early therapy group (0.1/100 person years) v. 27 in delayed therapy group (1.7/100 person years), HR=0.04, (p<0.001, 95% CI 0.04-0.27)

*Cohen at al NEJM 2011 365:493

HIV-related Complications

• Many SSA hospitals have adult ward HIV seroprevalence of 30-80%

• Most HIV-infected persons have advanced disease at the time of diagnosis

• Median CD4+ cell count 80-178

HIV and Tuberculosis

• Up to 30% of newly diagnosed HIV-infected persons have active TB

• Another 5-10%/year develop active TB• INH prophylaxis indicated but rarely used• Re-infection not uncommon

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Estimated HIV prevalence (%) among people newly infected with TB, 2006

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Number and percentage of notified TB cases who were tested for HIV in the 64 countries that reported data for each year from 2004 to 2006

HIV and TB in South Africa*

*Karim et al. The Lancet 374:921-933

Challenges in Hospitalization of TB and HIV Co-infected Patients

• Malawi- delay in TB treatment initiation >5 days after admission in 52%, >10 days in 15%

• Tanzania- 34% of inpatients are HIV-infected• Peru- HIV-infected patients with TB produce more infectious

quanta/hour (8.2) than historical HIV-uninfected controls (1.25)

• Diagnostic infrastructure, including susceptibility testing, is inadequate

• South Africa- nosocomial outbreaks are clearly occurring

Harries et al. Bull World Health Org 80:526;2002, Msaki et al. personal communication, Escombe et al. Clin Inf Dis 44:1349;2007, Ghandi et al. Lancet 368:1575;2006

Numbers of patients for whom DST was carried out at the start of treatment, and the number of patients with confirmed MDR-TB, by WHO region, 2005

Note that some countries reported the number of confirmed cases of MDR-TB without providing the number tested. Furthermore, confirmed MDR-TB cases may have been tested at any time during treatment.

Gandhi, et al. Lancet 2006 368: 1575-80

Guidelines for TB Infection Control• Administrative controls- reduce delays in diagnosis and

treatment, isolation of patients with infectious TB, surgical masks on patients when leaving isolation, exempting HIV-infected HCW’s from care

• Environmental controls- reduce droplet nuclei in high risk areas through ventilation and UV light

• Personal respiratory protection- respirators in high risk situations such as bronchoscopy or drug-resistant TB

Jensen et al. MMWR Recomm Rep 54:1;2005, WHO Guidelines for Prevention of TB in Health Care Facilities in Resource-limited settings 1999, Cobelens Clin Inf Dis 44:324;2007

Malignancies

• Cervical cancer- highly prevalent, screening inadequate, more progressive with lower CD4+ cell count, HPV types different

• Kaposi’s sarcoma• HPV-related squamous cell carcinomas of the

conjunctivae and oropharynx• Lymphoma

Evidence Base for Use of Co-trimoxazole Among HIV-infected Persons

• Reduced risk of death by 13-46% across CD4+ cell count strata, although frequently not significant at higher counts1-6

• Reduced risk of hospitalizations by 31-43%1,5 and clinic visits by 15%5

• Reduced unexplained fever2 and diarrhea5

• Reduced malaria2,5, pneumonia2, and Isospora enteritis2

1. Wiktor et al The Lancet 353:1469 1999 2. Anglaret et al The Lancet 353:1463 1999 3. Maynart et al JAIDS 26:130 2001 4. Badri et al AIDS 15:1143 2001 5. Mermin et al The Lancet 364:1428 2004 6. Mwangulu et al Bull WHO 82:354 2004

WHO Guidelines 2008

• If CD4 counts can be measured, recommend initiating co-trimoxazole at any WHO stage when CD4 count <350 (A-lll) or WHO stage 3 or 4 with any CD4 count (A-l)

• If CD4 counts cannot be measured, recommend initiating co-trimoxazole at WHO stage 2, 3 or 4 (A-l)

• Recommended dose is one double strength daily

Available at http://who.int/hiv/pub/guidelines/EP/en/index.html

Antiretroviral Treatment

Number of people receiving antiretroviral drugs in low- and middle income countries, 2002−2007

Source: Data provided by UNAIDS & WHO, 2008.

end-2002

end-2004

end-2003

end-2005

0.4

0.8

1.2

1.6

2.2

2.8

Mill

ions

Year

2.42.6

3.0

0.00.2

0.6

1.0

1.4

1.82.0

end-2007

end-2006

North Africa and the Middle East

Eastern Europe and Central Asia

East, South and South-East Asia

Latin America and the Caribbean

Sub-Saharan Africa

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Antiretroviral therapy coverage in the 15 countries accounting for 75% of the 3 million people receiving treatment in low- and middle-income

countries in 2007

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Median price (United States dollars) of first-line antiretroviral drug regimens in low-income countries, 2004-2007

2010 WHO Guidelines “Antiretroviral Therapy for HIV Infection in Adults and Adolescents”*

• HIV-related symptoms: Treat• CD4 <350 with or without symptoms: Treat• CD4 >350: Do not treat

*Antiretroviral Therapy for HIV-infected Adults and Adolescents 2010; http://www.who.int/hiv/pub/arv/adult/en/index.html

Earlier ART Improves Survival• Randomized trial at GHESKIO in Haiti1

• 816 adults with CD4 200-350• Randomized to start ART2 immediately, or when CD4 <200

or symptomatic disease• 6 deaths in immediate arm, 23 deaths in delayed arm• 18 developed TB in the immediate arm, 36 developed TB

in the delayed arm• Trial stopped early by DSMB

1. Severe et al. NEJM 2010; 363:2572. ART was ZDV, LMV and EFV

Figure 4.6

Antiretroviral therapy and mortality, Northwest Province, South Africa

Source: Ministry of Health, South Africa.

Number of people ever receiving antiretroviral therapy and annual number of deathsby age group, Northwest Province, South Africa, 1997–2007.

Figure 4.5

Antiretroviral therapy and TB incidence in Botswana

Source: Ministry of Health, Botswana.

Reported incidence of TB and number of people receiving antiretroviral therapy in Botswana, 1990–2007.

Linkage to Care* • Stage 1 (testing to receipt of CD4 count) 59% retained• Stage 2 (receipt of CD4 count to ART eligibility) 46%

retained• Stage 3 (ART eligibility to commencing drugs) 68% retained• Completion of all 3 stages 17%

*Rosen and Fox PLoS Med 2011

Figure 4.1

Adult retention in antiretroviral therapy in selected countries,0–48 months, 2009

Source: WHO Towards Universal Access 2010.

Consequences of Staying on a Virologically Failing Regimen

Murri R, et al. JAIDS. 2006;41:23-30.Losina E et al, 15th CROI 2008, #823Pillay D, et al. 14th CROI, Los Angeles 2007, #642

C D 4 C O U N T

VIRAL LOAD

VIROLOGIC FAILURE

IMMUNOLOGIC FAILURE

CLINICAL FAILURE

DRUG RESISTANCE

What is optimal schedule and method of following persons on ART…

• WHO does not specifically address this issue*• WHO recommends following clinical status, CD4

count (if available) and plasma HIV RNA (if available)• WHO outlines criteria for failure of regimen past 6

months

* Antiretroviral Therapy for HIV-infected Adults and Adolescents 2010; http://www.who.int/hiv/pub/arv/adult/en/index.html

Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

Median price (United States dollars) of second-line antiretroviral drug regimens in low-income countries, 2004-2007

Number and percentage of HIV-positive pregnant women receiving antiretroviral prophylaxis, 2004–2007

2004 20062005

Number of HIV-positive pregnant women receiving antiretrovirals

Year

400 000

500 000

600 000

0

100 000

200 000

300 000

% of HIV-positive pregnant women receiving antiretrovirals

0

5

30

35

15

20

25

40

10

2007

Source: UNAIDS, UNICEF & WHO, 2008; data provided by countries.

Conclusions• Encouraging trends in HIV prevalence• Prevention interventions offer efficacy, but

implementation science needed• HIV-TB interaction dominates clinical

management• ART roll-out appears successful to date, but

health systems strengthening is essential• Need guidance on optimal monitoring and

management