1. HIV/AIDS in Africa 2012 John A. Bartlett
Kilimanjaro Christian Medical Centre
Duke University Medical Center

2. 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
Objectives

3. A global view of HIV infection
33 million people [30–36 million] living with HIV, 2007

4. HIV prevalence in sub-Saharan Africa
Figure 2.7
HIV prevalence in sub-Saharan Africa
HIV prevalence among adults aged 15–49 years old in sub-Saharan Africa, 1990 to 2009.
1990
2002
1996
2009
Source:UNAIDS.

5. Changes in the incidence of HIV infection, 2001 to 2009
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-level
incidencewerealsoused.TheEPP/Spectrumcriteriaforincludingcountries inthis analysiswereasfollows. EPPfiles wereavailableandtrends inEPPwerenotderivedfrom workbook
prevalenceestimates; prevalence datawereavailableuptoatleast2007; therewereatleastfourtimepoints between2001and2009forwhichprevalencedatawereavailablefor
concentratedepidemicsandatleastthreedatapoints inthesameperiodforgeneralizedepidemics;forthemajority ofepidemic curves foragivencountry,EPPdidnotproduceanartificial
increaseinHIVprevalenceinrecentyears duetoscarcity ofprevalencedatapoints;datawererepresentativeofthecountry;theEPP/Spectrum–derivedincidencetrendwas notinconflict
withthetrendincasereports ofnew HIVdiagnoses; andtheEPP/Spectrum–derivedincidencetrendwasnotinconflictwithmodelledincidencetrends derivedfromage-specific prevalence
innationalsurvey results.
Source:UNAIDS.

6. Global HIV trends, 1990 to 2009 Number of people living with HIV
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.

7. HIV trends in sub-Saharan Africa
Figure 2.8
HIV trends in sub-Saharan Africa
Number of people living with HIV
Number of children living with HIV
Dotted lines represent ranges, solid lines represent the best estimate.
Number of people newly infected with HIV
Adult and child deaths due to AIDS
Source:UNAIDS.

8. Percent of adults (15+) living with HIV who are female, 1990–200710 20 30 40 50 60 70
Percent
female
(%)
Sub-Saharan Africa
GLOBAL
Caribbean
Asia
E Europe & C Asia
Latin America
1990
‘91
‘92
‘93
‘94
‘95
‘96
‘97
‘98
‘99
‘00
‘01
‘02
‘03
‘04
‘05
‘06
2007
Year 5

9. Prevention Testing Condoms Circumcision
Pre-exposure prophylaxis (PrEP)
Microbicides
Vaccines

10. Percentage of pregnant women in low- and midde-income countries receiving an HIV test, 2004-2007
Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

11. Condoms have proven efficacy!

12. Percentage of women and men aged 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,
Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

13. Male circumcision decreases HIV acquisition risk by 60%
Auvert et al PLoS Med 2:e ; Bailey et al The Lancet 369: ; Gray et al The Lancet 369:

14. Scaling up male circumcision
Table 3.2
Scaling up male circumcision
Recent roll-out of the scaling up of adult male circumcision in nine countries.
Number circumcised
Time period
Number of sites
established
BOTSWANA
KENYA
NAMIBIA
RWANDA
SWAZILAND
UGANDA
UNITED REPUBLIC OF TANZANIA
ZAMBIA
ZIMBABWE
6 180
91 300
( in Nyanza alone)
350
542
10 000
5 340
4 700
9 906
9 179
6 070
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 2010
2009
2007 – 2008
May 2009 – April 2010 35 3 9 56 5
Source: Meeting reports and presentations. Durham, NC, Clearinghouse on Male Circumcision for HIV Prevention, 2010.

15. Tenofovir 1% Gel Microbicide Decreases HIV Acquisition by 39%
Abdool Karim et al Science 2010; 329:1168

16. Heterologous HIV Vaccine Reduces Risk by 30%
Rerks-Ngarm et al. NEJM 2009; 361:2209

17. Pre-exposure Prophylaxis

18. 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 (
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)

19. HPTN 052* 1763 HIV-1 serodiscordant couples
Seropositive partner had CD
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 :493

20. 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 )
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 )
*Cohen at al NEJM :493

21. 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

22. 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

23. 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

24. 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
Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

25. HIV and TB in South Africa*
*Karim et al. The Lancet 374:

26. 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

27. 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.

28. Gandhi, et al. Lancet :

29. 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

30. 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

31. 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: Anglaret et al The Lancet 353: Maynart et al JAIDS 26: Badri et al AIDS 15: Mermin et al The Lancet 364: Mwangulu et al Bull WHO 82:

32. 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

33. Antiretroviral Treatment

34. Number of people receiving antiretroviral drugs
in low- and middle income countries, 2002−2007
Source: Data provided by UNAIDS & WHO, 2008.
end-
2002
2004
2003
2005
0.4
0.8
1.2
1.6
2.2
2.8
Millions
Year
2.4
2.6
3.0
0.0
0.2
0.6
1.0
1.4
1.8
2.0
2007
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

35. 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

36. Median price (United States dollars) of first-line antiretroviral drug regimens in low-income countries,
Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

37. HIV-related symptoms: Treat
CD4 <350 with or without symptoms: Treat
CD4 >350: Do not treat
2010 WHO Guidelines “Antiretroviral Therapy for HIV Infection in Adults and Adolescents”*
*Antiretroviral Therapy for HIV-infected Adults and Adolescents 2010;

38. Earlier ART Improves Survival
Randomized trial at GHESKIO in Haiti1
816 adults with CD
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
Severe et al. NEJM 2010; 363:257
ART was ZDV, LMV and EFV

39. Antiretroviral therapy and mortality, Northwest Province, South Africa
Figure 4.6
Antiretroviral therapy and mortality, Northwest Province, South Africa
Number of people ever receiving antiretroviral therapy and annual number of deaths
by age group, Northwest Province, South Africa, 1997–2007.
Source: Ministry of Health, South Africa.

40. Antiretroviral therapy and TB incidence in Botswana
Figure 4.5
Antiretroviral therapy and TB incidence in Botswana
Reported incidence of TB and number of people receiving antiretroviral therapy in Botswana, 1990–2007.
Source: Ministry of Health, Botswana.

41. 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

42. Adult retention in antiretroviral therapy in selected countries,
Figure 4.1
Adult retention in antiretroviral therapy in selected countries,
0–48 months, 2009
Source: WHO Towards Universal Access 2010.

43. Consequences of Staying on a Virologically Failing Regimen
VIROLOGIC FAILURE
IMMUNOLOGIC FAILURE
CLINICAL FAILURE
CD4 COUNT
DRUG RESISTANCE
Note to Speaker: This is a key slide in the presentation and should be strongly emphasized.
Key Points:
As virologic treatment failure occurs, the CD4 goes down (immunologic failure) and ultimately clinical failure ensues.
Virologic and sometimes immunologic failure, go unrecognized if VL and/or CD4 monitoring is not occurring. In this case, the patient stays on a failing regimen for a prolonged period of time, during which time resistance can occur. This will ultimately lead to increased morbidity and mortality, as discussed, and lead to fewer options in the future. The next few slides explain this process by sharing some data
VIRAL LOAD
Murri R, et al. JAIDS. 2006;41:23-30.
Losina E et al, 15th CROI 2008, #823
Pillay D, et al. 14th CROI, Los Angeles 2007, #642 43

44. 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;
What is optimal schedule and method of following persons on ART…

45. Median price (United States dollars) of second-line antiretroviral drug regimens in low-income countries,
Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

46. Number and percentage of HIV-positive pregnant women receiving antiretroviral prophylaxis, 2004–2007
2006
2005
Number of HIV-positive
pregnant women
receiving antiretrovirals
Year
% of HIV-positive 5 30 35 15 20 25 40 10
2007
Source: UNAIDS, UNICEF & WHO, 2008; data provided by countries.

47. 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
Conclusions