HIV/AIDS in Africa 2012

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

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

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

4. Figure2.7 HIVprevalenceinsub-SaharanAfrica HIVprevalence amongadultsaged 15–49 yearsold insub-SaharanAfrica,1990 to 2009. 1990 2002 1996 2009 Source:UNAIDS.

5. Figure2.2 ChangesintheincidenceofHIVinfection,2001to2009 Toassesschangesinincidence,theestimatednationalincidenceratewascomparedbetween2009and2001.Countrieswithachange(decreaseorincrease)intheincidencerateof25% ormoreduringthisperiodwereidentified.Inmostcases,theassessmentwasbasedonEPP/Spectrummodellingresults(1,2).Forselectedcountries,publishedanalysesofcountry-level incidencewerealsoused.TheEPP/Spectrumcriteriaforincludingcountriesinthisanalysiswereasfollows.EPPfileswereavailableandtrendsinEPPwerenotderivedfromworkbook prevalenceestimates;prevalencedatawereavailableuptoatleast2007;therewereatleastfourtimepointsbetween2001and2009forwhichprevalencedatawereavailablefor concentratedepidemicsandatleastthreedatapointsinthesameperiodforgeneralizedepidemics;forthemajorityofepidemiccurvesforagivencountry,EPPdidnotproduceanartificial increaseinHIVprevalenceinrecentyearsduetoscarcityofprevalencedatapoints;datawererepresentativeofthecountry;theEPP/Spectrum–derivedincidencetrendwasnotinconflict withthetrendincasereportsofnewHIVdiagnoses;andtheEPP/Spectrum–derivedincidencetrendwasnotinconflictwithmodelledincidencetrendsderivedfromage-specificprevalence innationalsurveyresults. Source:UNAIDS.

6. Figure2.5 GlobalHIVtrends,1990to2009 NumberofchildrenlivingwithHIV NumberoforphansduetoAIDS NumberofpeoplelivingwithHIV AdultandchilddeathsduetoAIDS Dottedlinesrepresentranges,solidlinesrepresentthebestestimate. Source:UNAIDS.

7. Figure2.8 HIVtrendsinsub-SaharanAfrica NumberofpeoplenewlyinfectedwithHIV AdultandchilddeathsduetoAIDS NumberofpeoplelivingwithHIV NumberofchildrenlivingwithHIV Dottedlinesrepresentranges,solidlinesrepresentthebestestimate. Source:UNAIDS.

8. Percent of adults (15+) living with HIV who are female, 1990–2007 70 Sub-Saharan Africa 60 GLOBAL 50 Percent female (%) Caribbean 40 Asia 30 E Europe & C Asia 20 Latin America 10 0 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 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 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:e298 2005; Bailey et al The Lancet 369:643 2007; Gray et al The Lancet 369:657 2007

14. Table3.2 Scalingupmalecircumcision Recentroll-outofthescalingupofadultmalecircumcisioninninecountries. Numbercircumcised Timeperiod Numberofsites established BOTSWANA KENYA NAMIBIA RWANDA SWAZILAND UGANDA UNITEDREPUBLICOFTANZANIA ZAMBIA ZIMBABWE 6180 91300 (90000inNyanzaalone) 350 542 10000 5340 4700 9906 10000 9179 6070 April2009–March2010 2009–June2010 September2009–June2010 October2009–April2010 2008–June2010 October2008–March2010 September2009–May2010 January–June2010 2009 2007–2008 May2009–April2010 35 3 9 3 56 5 Source:Meetingreportsandpresentations.Durham,NC,ClearinghouseonMaleCircumcisionforHIVPrevention,2010.

15. Tenofovir 1% Gel Microbicide Decreases HIV Acquisition by 39% AbdoolKarim 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 (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)

19. 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

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 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

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 80-178

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 374:921-933

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 2006 368: 1575-80

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 353:1469 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

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

33. Antiretroviral Treatment

34. Median price (United States dollars) of first-line antiretroviral drug regimens in low-income countries, 2004-2007 Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

35. 2013 WHO Guidelines for ART* • HIV-related symptoms: Treat • CD4 <500with or without symptoms: Treat • Treat the infected partner in a serodiscordant relationship • Treat all HIV-infected children under age 5 • Treat all pregnant and breastfeeding women • Treat all persons co-infected with TB or hepatitis B *Antiretroviral Therapy for HIV-infected Adults and Adolescents 2013; http://www.who.int/hiv/pub/arv/adult/en/index.html

36. 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 • Severe et al. NEJM 2010; 363:257 • ART was ZDV, LMV and EFV

37. Figure4.6 Antiretroviraltherapyandmortality,NorthwestProvince,SouthAfrica Numberofpeopleeverreceivingantiretroviraltherapyandannualnumberofdeaths byagegroup,NorthwestProvince,SouthAfrica,1997–2007. Source:MinistryofHealth,SouthAfrica.

38. Figure4.5 AntiretroviraltherapyandTBincidenceinBotswana ReportedincidenceofTBandnumberofpeoplereceivingantiretroviraltherapyinBotswana,1990–2007. Source:MinistryofHealth,Botswana.

39. 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

40. Figure4.1 Adultretentioninantiretroviraltherapyinselectedcountries, 0–48months,2009 Source:WHOTowardsUniversalAccess2010.

41. Consequences of Staying on a Virologically Failing Regimen VIROLOGIC FAILURE IMMUNOLOGIC FAILURE CLINICAL FAILURE CD4 COUNT DRUG RESISTANCE 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

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

43. Median price (United States dollars) of second-line antiretroviral drug regimens in low-income countries, 2004-2007 Towards Universal Access – Scaling up priority HIV/AIDS interventions in the health sector. WHO/UNAIDS/UNICEF, June 2008

44. HIV and aging in Africa In 2040, the number of persons over 50 years of age living with HIV is expected to be 9 million Mills et al., N Engl J Med 2012; 366:14

45. 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