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

Objectives To describe current trends in HIV/AIDSepidemiology in SSA To describe current prevention efforts in SSA To describe HIV-related complications in SSA To describe the current status of antiretroviraltherapy in SSA

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

Figure 2.7 HIV prevalence in sub-Saharan Africa HIV prevalence among adults aged 15–49 years old in sub-Saharan Africa, 1990 to 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-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.

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.

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,

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 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,

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:

April 2009 – March – June 2010 September 2009 – June 2010 October 2009 – April – June 2010 October 2008 – March 2010 September 2009 – May 2010 January – June – 2008 May 2009 – April ( in Nyanza alone) BOTSWANA KENYA NAMIBIA RWANDA SWAZILAND UGANDA UNITED REPUBLIC OF TANZANIA ZAMBIA ZIMBABWE Number of sites established Time periodNumber circumcised Table 3.2 Scaling up male circumcision Recent 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 ( 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 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

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

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

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:

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 :

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 counts 1-6 Reduced risk of hospitalizations by 31-43% 1,5 and clinic visits by 15% 5 Reduced unexplained fever 2 and diarrhea 5 Reduced malaria 2,5, pneumonia 2, and Isospora enteritis 2 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:

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

Antiretroviral Treatment

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,

2013 WHO Guidelines for ART* HIV-related symptoms: Treat CD4 <500 with or without symptoms: Treat Treat the infected partner in a serodiscordantrelationship Treat all HIV-infected children under age 5 Treat all pregnant and breastfeeding women Treat all persons co-infected with TB orhepatitis B *Antiretroviral Therapy for HIV-infected Adults and Adolescents 2013;

Earlier ART Improves Survival Randomized trial at GHESKIO in Haiti adults with CD Randomized to start ART 2 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; 363:257 2.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 deaths by 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: Losina E et al, 15th CROI 2008, #823 Pillay D, et al. 14th CROI, Los Angeles 2007, #642 CD4 COUNT VIRAL LOAD VIROLOGIC FAILURE IMMUNOLOGIC FAILURE CLINICAL FAILURE DRUG RESISTANCE

What is optimal schedule and method of following persons on ART… WHO recommends following clinical status,CD4 count (if available) and plasma HIV RNA (ifavailable) WHO outlines criteria for failure of regimenpast 6 months * Antiretroviral Therapy for HIV-infected Adults and Adolescents 2010;

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,

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

Conclusions Encouraging trends in HIV prevalence Prevention interventions offer efficacy, butimplementation science needed HIV-TB interaction dominates clinicalmanagement ART roll-out appears successful to date, buthealth systems strengthening is essential Need guidance on optimal monitoring andmanagement