HIV This Week

Burden of HIV among female sex workers in low-income and middle-income countries: a systematic review and meta-analysis

Baral S, Beyrer C, Muessig K, Poteat T, Wirtz AL, Decker MR, Sherman SG, Kerrigan D. Lancet Infect Dis. 2012 Mar 14. [Epub ahead of print]

Female sex workers are a population who are at heightened risk of HIV infection secondary to biological, behavioural, and structural risk factors. However, three decades into the HIV pandemic, understanding of the burden of HIV among these women remains limited. Baral and colleagues aimed to assess the burden of HIV in this population compared with that of other women of reproductive age. They searched PubMed, Embase, Global Health, SCOPUS, PsycINFO, Sociological Abstracts, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Web of Science, and POPLine for studies of female sex workers in low-income and middle-income countries published between Jan 1, 2007, and June 25, 2011. Studies of any design that measured the prevalence or incidence of HIV among female sex workers, even if sex workers were not the main focus of the study, were included. Meta-analyses were done with the Mantel-Haenszel method with a random-effects model characterising an odds ratio for the prevalence of HIV among female sex workers compared with that for all women of reproductive age. Of 434 selected articles and surveillance reports, 102 were included in the analyses, representing 99 878 female sex workers in 50 countries. The overall HIV prevalence was 11.8% (95% CI 11.6-12.0) with a pooled odds ratio for HIV infection of 13.5 (95% CI 10.0-18.1) with wide intraregional ranges in the pooled HIV prevalence and odds ratios for HIV infection. In 26 countries with medium and high background HIV prevalence, 30.7% (95% CI 30.2-31.3; 8627 of 28 075) of sex workers were HIV-positive and the odds ratio for infection was 11.6 (95% CI 9.1-14.8). Although data characterising HIV risk among female sex workers are scarce, the burden of disease is disproportionately high. These data suggest an urgent need to scale up access to quality HIV prevention programmes. Considerations of the legal and policy environments in which sex workers operate and actions to address the important role of stigma, discrimination, and violence targeting female sex workers is needed.

For abstract access click here. 

Editor’s note: This is the first systematic documentation of the scope and breadth of the disproportionate HIV infection risk that female sex workers bear around the world and the findings are striking. First, only 50 of 145 low- and middle-income countries have published data including measurement of HIV status among female sex workers in the past 5 years. These data gaps are likely due in part to social stigma, criminalisation of sex work, and the USA ‘Prostitution Pledge’ that reduced research interest and funding for studies among sex workers. Without data it is impossible to know whether adequate programming resources are in place and whether they are having the intended impact. Second, sex work, defined here as the exchange of sex for money, carries an occupational risk of HIV infection that is more than 13 times that found in other women of similar age. Sex workers in countries with high HIV prevalence among all women, such as those in sub-Saharan Africa, have lower odds of HIV infection compared to other women than do those in countries with low HIV prevalence, such as India where the risk is 50 times higher. Each country needs to address the structural risk factors that heighten this risk, including legal and regulatory policies and the organisation and power dynamics of sex work. Increasing coverage of HIV prevention programmes, supporting empowerment of sex workers to reduce their risk, and scaling up access for female sex workers living with HIV to antiretroviral treatment for both clinical and prevention benefits are among the urgently needed steps to address the high HIV burden borne by these women.

Immune-correlates analysis of an HIV-1 vaccine efficacy trial

Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, Berman PW, Frahm N, De Rosa SC, Alpert MD, Yates NL, Shen X, Koup RA, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Michael NL, Kim JH. N Engl J Med. 2012 Apr 5;366(14):1275-86

In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. Haynes and colleagues performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P=0.02; q=0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P=0.03; q=0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies. This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.

For abstract access click here. 

Editor’s note: These findings are so intriguing! And they are quite amazing, because the samples available from RV144, the trial that many thought should be stopped as probably futile, were so few in the end. This well designed study used samples from the vaccine regimen arm (see HIV This Week Issue 74 for details) and compared those who became infected with those who did not in a 5 to 1 ratio. The researchers narrowed down the search to 6 immune parameters and 2 proved significant: one of which was associated with decreased risk of HIV acquisition (IgG against the V1V2 variable loop) and one which appeared to be associated with a lack of protection without increasing the risk of HIV acquisition itself (Env-specific IgA antibodies). The latter counters the protective effects of other responses the body is mounting when exposed to HIV and it had been seen with exposure to other pathogens, in the regulation of autoantibody function, and in immune responses to cancer. These findings are exciting on at least two levels. First, they are hypothesis-generating with regard to immune responses required for protection and they can improve the selection of primary end-points in future HIV vaccine trials. Second, if the protection of V1V2 antibodies can be confirmed then vaccine efficacy might improve with vaccines specifically designed to induce high levels of V1V2 IgG antibodies and low levels of Env-specific antibodies.

Expanding ART for treatment and prevention of HIV in South Africa: Estimated cost and cost-effectiveness 2011-2050

Granich R, Kahn JG, Bennett R, Holmes CB, Garg N, Serenata C, Sabin ML, Makhlouf-Obermeyer C, De Filippo Mack C, Williams P, Jones L, Smyth C, Kutch KA, Ying-Ru L, Vitoria M, Souteyrand Y, Crowley S, Korenromp EL, Williams BG. PLoS One. 2012;7(2):e30216. Epub 2012 Feb 13

Antiretroviral treatment (ART) significantly reduces HIV transmission. Granich and colleagues conducted a cost-effectiveness analysis of the impact of expanded antiretroviral treatment in South Africa. The authors modelled a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four antiretroviral treatment eligibility scenarios: CD4 count <200 cells/mm(3) (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and antiretroviral treatment costs reflect South African data and international generic prices. Antiretroviral treatment reduces transmission by 92%. The authors conducted sensitivity analyses. Expanding antiretroviral treatment to CD4 count <350 cells/mm(3) prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher antiretroviral treatment and monitoring costs, all CD4 levels saves $0.6 billion versus current; other antiretroviral treatment scenarios cost $9-194 per DALY averted. If antiretroviral treatment reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Increasing the provision of antiretroviral treatment to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated.

For abstract access click here. 

Editor’s note: The 2010 WHO recommendations for antiretroviral treatment initiation increased the CD4 count eligibility level from under 200 cells/uL to under 350 cells/uL, after expert review of the scientific evidence concluded that the benefits of earlier HIV treatment are tangible and valuable. This expanded the numbers of those eligible for treatment globally by 50%, with the result that countries adopting the new Guidelines  - and many did - saw their per cent achievement towards universal access for antiretroviral treatment drop. South Africa opted to expand treatment at CD4 350 first to pregnant women and tuberculosis-coinfected patients and then, in August 2011, to all those with CD4 counts at or below 350. This economic analysis provides a vision of the potential costs of earlier treatment balanced against the savings from lowered future treatment demand as a result of infections averted with this policy decision. The analysis also examines the options of treatment initiation at 500 cells/uL and treatment initiation regardless of CD4 count. Some of parameters seem unrealistic (e.g.1.5% annual programme drop-out, 5-year scale-up horizon to 90% for sustained annual HIV testing and sustained 90% antiretroviral treatment coverage [regardless of gender or HIV exposure risk], no consideration of the potential impact of antiretroviral drug resistance, and no viral load testing to inform adherence counselling and the need for switching regimens in the base case scenario. However, the case for front-loaded investment in earlier antiretroviral therapy is compelling nonetheless. This model predicts that South Africa’s change to 350 cells/uL will pay for itself in 4 to 12 years as care shifts from inpatient to ambulatory HIV care and disease burden declines through both direct health benefits and collateral prevention spin-offs of expanded treatment scale-up.

Children who acquire HIV infection perinatally are at higher risk of early death than those acquiring infection through breastmilk: A meta-analysis

Becquet R, Marston M, Dabis F, Moulton LH, Gray G, Coovadia HM, Essex M, Ekouevi DK, Jackson D, Coutsoudis A, Kilewo C, Leroy V, Wiktor SZ, Nduati R, Msellati P, Zaba B, Ghys PD, Newell ML; the UNAIDS Child survival group. PLoS One. 2012;7(2):e28510. Epub 2012 Feb 23

Assumptions about survival of HIV-infected children in Africa without antiretroviral therapy need to be updated to inform ongoing UNAIDS modelling of paediatric HIV epidemics among children. Improved estimates of infant survival by timing of HIV-infection (perinatally or postnatally) are thus needed. A pooled analysis was conducted of individual data of all available intervention cohorts and randomized trials on prevention of HIV mother-to-child transmission in Africa. Studies were right-censored at the time of infant antiretroviral initiation. Overall mortality rate per 1000 child-years of follow-up was calculated by selected maternal and infant characteristics. The Kaplan-Meier method was used to estimate survival curves by child's HIV infection status and timing of HIV infection. Individual data from 12 studies were pooled, with 12,112 children of HIV-infected women. Mortality rates per 1,000 child-years follow-up were 39.3 and 381.6 for HIV-uninfected and infected children respectively. One year after acquisition of HIV infection, an estimated 26% postnatally and 52% perinatally infected children would have died; and 4% uninfected children by age 1 year. Mortality was independently associated with maternal death (adjusted hazard ratio 2.2, 95%CI 1.6-3.0), maternal CD4<350 cells/ml (1.4, 1.1-1.7), postnatal (3.1, 2.1-4.1) or peri-partum HIV-infection (12.4, 10.1-15.3). These results update previous work and inform future UNAIDS modelling by providing survival estimates for HIV-infected untreated African children by timing of infection. The authors highlight the urgent need for the prevention of peri-partum and postnatal transmission and timely assessment of HIV infection in infants to initiate antiretroviral care and support for HIV-infected children.

For abstract access click here.

Editor’s note: Although this analysis was done with a view to improving UNAIDS’ mortality estimates, the policy implications for programmes aimed at preventing paediatric HIV infection are clear. Of the 12 trials or studies investigating ways to reduce the risk of paediatric HIV acquisition that were included in this analysis, only one made paediatric HIV treatment available at the time of the study. Thus these findings represent baseline child survival by timing of HIV infection - and they are striking. Children who acquired HIV during pregnancy and delivery were 12 times more likely to die by age 1 than were uninfected children born to mothers living with HIV infection. For children infected through breastfeeding, mortality risk was 3 times higher, and for those with an unknown timing of HIV infection it was intermediate, at 7 times higher. Children who were never breastfed were twice as likely to die than ever breastfed children, as were children whose mothers died during follow-up. We have known for a long time that without antiretroviral treatment and care 50% of children infected perinatally do not survive to age 2. These findings of differential survival by timing of infection underscore the importance of early detection of HIV infection in pregnant women with timely initiation of antiretroviral prophylaxis to prevent HIV transmission in utero, labour, and delivery. But ideally this should be full antiretroviral therapy for life to keep mothers alive and healthy so that they can breastfeed their infants and care for them.