HIV This Week

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Renee Heffron, Deborah Donnell, Prof Helen Rees, Connie Celum, Nelly Mugo, Edwin Were, Guy de Bruyn, Edith Nakku-Joloba, Kenneth Ngure, James Kiarie, Robert W Coombs, Jared M Baeten, The Lancet Infectious Diseases, Early Online Publication, 4 October 2011

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Heffron and colleagues aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, they followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, they compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. Cox proportional hazards regression and marginal structural modelling were used to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6–24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8–24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.

For abstract access click here

Editor’s note: The issue of hormonal contraception and HIV risk continues to perplex. Observational studies have both suggested a link and not found one. This study of HIV serodiscordant couples was not specifically designed to examine this issue and had too few women on contraceptive pills to draw any conclusions. However, a doubling of the risk of HIV acquisition for HIV-negative women using injectable DMPA (depot-medroxyprogesterone acetate) and a doubling of the risk of HIV transmission from HIV-positive women using DMPA to their seronegative partners are cause for concern. Contraception improves the health of women and children worldwide and it plays a crucial role in helping women with, or at risk of, HIV infection to prevent the adverse social and health consequences of unintended pregnancies. WHO and partners are convening a technical consultation in early 2012 to re-examine the totality of evidence on the potential effects of hormonal contraception and of intrauterine devices on HIV acquisition, disease progression, and infectivity/transmission to sexual partners. The need to conduct randomized controlled trials to determine whether hormonal contraception increases the risk of HIV acquisition in women and/or of HIV transmission to men will be assessed, along with feasibility. In the meantime, we need to reinforce the importance of correct and consistent condom use, regardless of whether another method of contraception is being used. It is and has been for decades the ‘dual protection’ message.

Adult male circumcision as an intervention against HIV: an operational study of uptake in a South African community (ANRS 12126)

Lissouba P, Taljaard D, Rech D, Dermaux-Msimang V, Legeai C, Lewis D, Singh B, Puren A, Auvert B. BMC Infect Dis. 2011 Sep 26;11(1):253.

The objective of this study was to evaluate the knowledge, attitudes, and beliefs about adult male circumcision, assess the association of adult male circumcision with HIV incidence and prevalence, and estimate adult male circumcision uptake in a Southern African community. A cross-sectional biomedical survey (ANRS-12126) was conducted in 2007-2008 among a random sample of 1198 men aged 15 to 49 from Orange Farm (South Africa). Face-to-face interviews were conducted by structured questionnaire. Recent HIV infections were evaluated using the BED incidence assay. Circumcision status was self-reported and clinically assessed. Adjusted HIV incidence rate ratios and prevalence ratios were calculated using Poisson regression. The response rate was 73.9%. Most respondents agreed that circumcised men could become HIV infected and needed to use condoms, although 19.3% (95%CI: 17.1% to 21.6%) asserted that adult male circumcision protected fully against HIV. Among self-reported circumcised men, 44.9% (95%CI: 39.6% to 50.3%) had intact foreskins. Men without foreskins had lower HIV incidence and prevalence than men with foreskins (aIRR=0.35; 95%CI: 0.14 to 0.88; aPR=0.45, 95%CI: 0.26 to 0.79). No significant difference was found between self-reported circumcised men with foreskins and other uncircumcised men. Intention to undergo adult male circumcision was associated with ethnic group and partner and family support of adult male circumcision. Uptake of adult male circumcision was 58.8% (95%CI: 55.4% to 62.0%). Adult male circumcision uptake in this community is high but communication and counselling should emphasize what clinical adult male circumcision is and its effect on HIV acquisition. These findings suggest that adult male circumcision roll-out is promising but requires careful implementation strategies to be successful against the African HIV epidemic.

For abstract access click here

Editor’s note: This first study to examine uptake of voluntary medical male circumcision (VMMC) among a random sample of the general population produced interesting findings. The most salient are the 55% lower HIV prevalence and 65% lower incidence in clinically circumcised men – the latter is more than the risk reduction of 60% seen in the randomised controlled trial conducted before 2005 in the same setting. More important from the point of view of programming is that 45% of men who reported that they were circumcised were found to have foreskins when they were examined. Men who have undergone initiation rituals may call themselves circumcised even if they have an intact foreskin. This suggests the importance of community education for both men and women, perhaps involving photos, about what a circumcised penis looks, along with information on the benefits of VMMC in high HIV prevalence settings. 81% of uncircumcised men in the study stated their intention to undergo VMMC and 72% of these were circumcised through the study (59% uptake). The most important factors influencing the decision to undergo VMMC were being from a traditionally circumcising ethnic group, believing that VMMC was safe, and having partner and family support. 

HIV attitudes, awareness and testing among older adults in Africa

Negin J, Nemser B, Cumming R, Lelerai E, Ben Amor Y, Pronyk P. AIDS Behav. 2011 Jul 8.

In Africa, older adults aged 50 and older are still sexually active and play a critical role as caregivers, yet little is known about their attitudes towards HIV and awareness of services. In this study, surveys were conducted in nine African sites. A multilevel model was fitted to evaluate the relationship between age and outcome variables. The study reveals that people aged 50 years and older have lower levels of HIV-related knowledge and awareness than those aged 25-49. Older adults were less likely to have been tested for HIV and women aged 50 and older showed particularly low levels of awareness.

For abstract access click here

Editor’s note: In 2010, a study estimated that 3 million people aged 50 and over were living with HIV in sub-Saharan Africa, representing fully 14% of those over age 15 with HIV infection. Some of these people have aged into this age category due to the life-prolonging benefits of antiretroviral therapy but others are becoming newly infected each day. Many do not know that they have HIV infection. Why do we never hear about older people with HIV? Our HIV prevention progress indicators for sexual transmission refer to people aged 15-49 years and prevalence data collected through Demographic and Health Surveys (DHS) and presented by UNAIDS do not include people aged 50 years and older. This measurement neglect is reflected in lack of programming to raise awareness and knowledge levels, develop communication and condom negotiation skills, and address stigma and discrimination in this age group commonly seen primarily as a caregiver source. Some countries are jumping ahead: South Africa has held caregiver workshops to improve attitudes and knowledge and has added males older than 50 to its list of most-at-risk populations (key populations). Across the nine clusters in eight countries in this Millennium Villages Project study, the lowest ‘ever tested for HIV’ levels were in Senegal (0% for both men and women) and the highest in Rwanda (23% for men and 17% for women). More attention to people aged 50 and older is needed now if they are to avoid HIV infection, access HIV testing, start timely antiretroviral treatment, and have a positive intergenerational influence on community attitudes and knowledge as sexually active and informed educators, as well as caretakers.

Long-term costs and health impact of continued global fund support for antiretroviral therapy

Stover J, Korenromp EL, Blakley M, Komatsu R, Viisainen K, Bollinger L, Atun R. PLoS One. 2011;6(6):e21048.

By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy in 104 low- and middle-income countries. Stover and colleagues estimated the cost and health impact of continuing treatment for these patients through 2020. Survival on first-line and second-line antiretroviral therapy regimens is estimated based on annual retention rates reported by national AIDS programmes. Costs per patient-year were calculated from country-reported antiretroviral procurement prices, and expenditures on laboratory tests, health care utilisation, and end-of-life care from in-depth costing studies. Of the 3.5 million patients on antiretroviral therapy in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining antiretroviral therapy falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T), or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by antiretroviral therapy correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens.

For abstract access click here

Editor’s note: This analysis of the cost and impact of continuing treatment for the 3.5 million of people who are co-supported by the Global Fund, compared to stopping it, provides food for thought. For the 6.6 million people on antiretroviral therapy now, retention on treatment is excellent after the first year, based on data from 38 national AIDS programmes in 2008: 80% not dying or lost to follow-up at 1 year, 75% at 2 years, 74% at 3 years, and 73% at 4 years. If treatment were to be stopped now for those receiving it, 18% would die in the first year, 46% after two years, 64% after three years, 76% after 4 years, 84% after 5 years, and 97% after 6 years. Median survival after treatment cessation would be 2 to 3 years. If the Global Fund did not support any new people to start antiretroviral therapy, the costs to maintain those already on treatment through to 2020 would decline. Costs increase as more people are moved off d4T first-line regimens or start costly second-line regimens (24% will likely be on second-line by 2020), however deaths result in 10% reduced costs overall. Antiretroviral drugs constitute 42% of first-line regimen and 81% of second-line regimen costs, underscoring the importance of further price reductions. Routine viral load testing, CD4 cunts, and clinical monitoring for timely detection of and responses to adherence difficulties, will prevent unnecessary switching to second-line regimens. The most striking finding is the number of life-years saved each year¾it rises to 2.3 million by 2017 when virtually everyone treated today would have died in the absence of treatment. Setting aside moral, ethical, and treatment for prevention arguments, continued and increased investment in antiretroviral treatment makes economic sense, not only for those already on treatment but also for those eligible and waiting.