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
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
2013 WHO Guidelines for ART*
• HIV-related symptoms: Treat
• CD4 <500 with 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
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 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
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, 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
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