HIV This Week

Powers KA, Poole C, Pettifor AR, Cohen MS. Rethinking the heterosexual infectivity of HIV-1: a systematic review and meta-analysis. Lancet 2008 Published online August 5, 2008 DOI:10.1016/S1473-3099(08)70156-7

Studies of cumulative HIV incidence suggest that cofactors such as genital ulcer disease, HIV disease stage, and male circumcision influence HIV transmission; however, the heterosexual infectivity of HIV-1 is commonly cited as a fixed value (approximately 0∙001, or one transmission per 1000 contacts). Powers et al sought to estimate transmission cofactor effects on the heterosexual infectivity of HIV-1 and to quantify the extent to which study methods have affected infectivity estimates. They undertook a systematic search (up to April 27, 2008) of PubMed, Web of Science, and relevant bibliographies to identify articles estimating the heterosexual infectivity of HIV-1. They used meta-regression and stratified random-effects meta-analysis to assess differences in infectivity associated with cofactors and study methods. Infectivity estimates were very heterogeneous, ranging from zero transmissions after more than 100 penile-vaginal contacts in some serodiscordant couples to one transmission for every 3∙1 episodes of heterosexual anal intercourse. Estimates were only weakly associated with study methods. Infectivity differences, expressed as number of transmissions per 1000 contacts, were 8·1 (95 % CI 0·4–15·8) when comparing uncircumcised to circumcised susceptible men, 6·0 (3·3–8·8) comparing susceptible individuals with and without genital ulcer disease, 1·9 (0·9–2·8) comparing late-stage to midstage index cases, and 2·5 (0·2–4·9) comparing early-stage to mid-stage index cases. A single value for the heterosexual infectivity of HIV-1 fails to reflect the variation associated with important cofactors. The commonly cited value of 0∙001 was estimated among stable couples with low prevalences of high-risk cofactors, and represents a lower bound. Cofactor effects are important to include in epidemic models, policy considerations, and prevention messages.

Editors’ note: The findings of this systematic analysis suggest that in many contexts, such as lack of male circumcision, presence of sexually transmitted infections, practice of anal sex, and early-stage or late-stage infection, heterosexual infectivity of HIV-1 might exceed the commonly cited value of one-in-a-thousand by more than an order of magnitude (i.e. more than one-in-a-hundred). Other cofactors, for which there are insufficient data but that clearly may play a role, such as viral load, viral subtype, and antiretroviral drug use, can further increase or decrease transmission probabilities. Since the overall probability of HIV transmission also depends on the probability of exposure to HIV in the first place, we need to work on the determinants of exposure as well as the co-factors for transmission.

Few longitudinal studies have described the interactions between reactivation of herpes simplex virus type 2 (HSV-2) infection (hereafter, "HSV-2 reactivation") and genital and systemic replication of human immunodeficiency virus type 1 (HIV-1). Women in Burkina Faso who were seropositive for both HIV-1 and HSV-2 were enrolled in a randomized placebo-controlled trial of therapy to suppress reactivation of HSV-2 infection (hereafter, "HSV suppressive therapy"). During the baseline phase, 6 enriched cervicovaginal lavage specimens were obtained over 12 weeks to detect and quantify the HIV-1 RNA and HSV-2 DNA loads. Women with genital ulcer disease (GUD) detected at least once were more likely than women in whom GUD was not detected (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.09-1.37) to have genital HIV-1 RNA detected during >or=1 visit. Similarly, women with genital HSV-2 DNA detected during >or=1 clinic visit were more likely than women in whom genital HSV-2 DNA was not detected (RR, 1.17; 95% CI, 1.01-1.34) to have genital HIV-1 RNA detected at least once . In addition, the mean genital HIV-1 RNA loads for women with GUD detected during >or=1 visit and women with HSV-2 genital shedding detected during >or=1 visit were greater than that for women in whom genital HSV-2 DNA or GUD was never detected. The plasma HIV-1 RNA load was increased among women for whom >or=1 visit revealed GUD (+0.25 log(10) copies/mL; 95% CI, -0.05-0.55) or genital HSV-2 DNA (+0.40 log(10) copies/mL; 95% CI, 0.15-0.66), compared with women who did not experience GUD or HSV-2 genital shedding, respectively. The association of HSV-2 reactivations on HIV-1 replication tended to be stronger in patients with a higher CD4(+) cell count (i.e., >500 cells/microL). The contribution of HSV-2 to HIV-1 replication among women with CD4(+) cell count of <or=500 cells/microL was reduced because almost all experienced HIV-1 genital shedding. Both clinical and subclinical HSV-2 reactivations play a role in increasing the rate of HIV-1 replication. HSV suppressive therapy is a promising tool for HIV control. Initiation of such therapy when the CD4(+) cell count is >500 cells/microL deserves further investigation.

Editors’ note: More than 70% of people living with HIV in high-income, middle-income, and low-income countries may be co-infected with herpes simplex virus type 2 (HSV-2). This study of 136 women who were moderately immunosuppressed but not on antiretroviral treatment and who contributed data from 784 study visits, demonstrates that both clinical (i.e. symptomatic with genital ulcers) and subclinical (i.e. no symptoms) HSV-2 reactivations contribute to HIV replication in the plasma and to genital HIV shedding. Because HSV-2 suppressive therapy has the potential to both prevent onward transmission and slow HIV disease progression, consideration may be given to offering it to people with known HIV–positive status who present with genital ulcer disease, to take until they become eligible for antiretroviral treatment, pending further studies.

Vissers DCJ, Voeten HACM, Urassa M, Isingo R, Ndege M, Kumogola Y, Mwaluko G, Zaba B, De Vlas SJ and Habbema JDF. Separation of spouses due to travel and living apart raises HIV risk in Tanzanian couples. Sexually Transmitted Diseases, August 2008, Vol. 35, No. 8, p.714–720

Persons with absent partners may be more vulnerable to risky sexual behaviour and therefore HIV. Partner absence can be due to travelling (e.g. family visits or funerals) or to living apart (e.g. work-related or in polygamous marriages). Debby et al investigated to what extent partner absence leads to more risky sexual behaviour in Tanzanian couples. They compared 95 men and 85 women living apart with 283 men and 331 women living together. Only persons who were still married were included, either living apart or cohabiting at the time of the interview. Subjects were classified into 4 groups: coresidents being either nonmobile or mobile, and people living apart either frequently or infrequently seeing each other. Most people living apart were polygamously married. Men living apart did not report more extramarital sex than coresident men. However, among coresident men, extramarital sex was reported by 35% of those being mobile compared with 15% of those nonmobile. Among women, those living apart reported extramarital sex more often than coresidents (14% vs. 7%), and this was mainly due to women living apart who infrequently saw their husbands. Risky sexual behaviour occurs more often in mobile coresident men, and in women living apart infrequently seeing their spouses. These groups are relatively easy to identify and need extra attention in HIV prevention campaigns.

Editors’ note: Concurrent relationships, multiple partners, and mobility are known to be associated with an increased risk of HIV exposure. The results of this study of couples, who were co-resident in 1996 and still married in 2002 according to both partners, emphasise the importance of studying the sexual behaviour of both sexes. Although most couples living apart in this area of north-western Tanzania were in polygamous marriages, living apart was not associated with increased extramarital sex in men but it was in women. Being mobile was a risk factor for unprotected extramarital sex in men but not in women. Promoting condom use for extramarital encounters is an obvious first step but a better understanding of the determinants of sexual risk behaviour in women living apart is needed to inform effective prevention programmes.

Nigeria is home to more people living with HIV than any other country in the world, except South Africa and India - where an estimated 2.9 million [1.7 million - 4.2 million] people were living with the virus in 2005. Women bear the greatest burden of frequent high-risk pregnancies, raising large families, and increasingly, the AIDS epidemic. Thus, there is a need for better understanding of the determinants of high risk sexual behaviour among women. In this study, Uthman et al examined factors associated with extra-marital sex among women in Nigeria and investigated how much variation in reported extra-marital sex can be attributed to individual-, and community-level factors. Uthman et al analyzed data from 6362 sexually active women aged 15 - 49 years who participated in the Nigeria 2003 Demographic and Health Survey using multilevel logistic regression models. Results are presented as odds ratio with 95% confidence interval. Independent of other factors, compared to women aged 15-24 years, those 25 - 34 years (odds ratio [OR] 0.59; 95% CI: 0.44 - 0.79) and 35 years or older (OR 0.36; 95% CI: 0.24 - 0.54) were less likely to have reported multiple concurrent sex partners in the last 12 years. As expected, women currently or formerly married were less likely to have reported multiple concurrent sex partners than women never married. Women who drank alcohol in the last three months were more likely to have reported multiple concurrent sex partners. Compared to women from richest household, women from poorest and middle household were 83% and 51% more likely to have multiple concurrent sex partners in the last 12 month respectively. After individual compositional and contextual factors, community wealth status was statistically significant with sexual behaviour. The study has demonstrated that individual and community wealth status are independent predictors of women's sexual behaviour, and that there is significant neighbourhood variation in odds of multiple concurrent sex partners, even after controlling for effects of both individual- and community-level characteristics. Scholars trying to understand variation individual high risk sexual behaviour should pay attention to the characteristics of both individuals and places of residence.

Editors’ note: Although this study has a large sample size, it suffers from its vague definition of the high-risk sexual behaviour ‘multiple concurrent partners’. This is defined as ‘having two or more sex partners in the last 12 months’. Such a definition lumps together women who became widows or divorced or left a partnership earlier in the year and then entered a new partnership (with no concurrency), women who exchange sex for money at high frequency (possibly with no concurrency, depending on your definition, unless they have regular clients or an ongoing boyfriend/husband), and women with concurrent partnerships. It makes sense that sexually active unmarried women, women who drink alcohol, or women from poor or middle-income households, are more likely to have two or more partners in the previous 12 months but no evidence is presented to suggest that these are concurrent partnerships, let alone ‘multiple’ concurrent partnerships.

Souteyrand YP, Collard V, Moatti JP, Grubb I, Guerma T. Free care at the point of service delivery: a key component for reaching universal access to HIV/AIDS treatment in developing countries. AIDS. 2008 Jul;22 Suppl 1:S161-8.

User fees are a common feature of health system financing in low and middle-income countries. In the context of universal access to HIV treatment and care, the advantages of user fees for funding at country and local level should be balanced with their clinical and public health impact. Souteyrand et al reviewed the literature on user fees and the impact of user fees on HIV service delivery. Empirical evidence gathered since the 1980s shows that sustainability, efficiency and equity challenges faced by health systems have persisted with and have often been exacerbated by the introduction of user fees. The evidence on HIV suggests that free care at the point of service fosters uptake and helps to extend access for the poorest users. User fees are currently the main barrier to adherence to antiretroviral therapy. Their abolition is associated with better virological results and increased survival. Such abolition should be carried out in parallel with the implementation of financing mechanisms, such as prepayment and risk pooling, which are able to gather funds from the sectors of the population who are able to pay for healthcare and to promote equity towards the poorest. WHO has included free access to HIV treatment at the point of service delivery as a component of its public health approach for reaching universal access. Implementation of free HIV care should, however, be linked to efforts to strengthen healthcare systems, ensure long-term sustainability of funding and monitor equity of access to care.

Editors’ note: Financial barriers cannot be allowed to provoke non-adherence and compromise first-line treatment regimens. In March 2005, countries were advised to adopt a policy of free access to HIV treatment at the point of service delivery, following a WHO/UNAIDS/World Bank consultation. Abolition of user fees and introduction or strengthening of more equitable funding mechanisms can create positive spillover that increases access and strengthens health care infrastructure as a whole.

The number of people in the world living with HIV is increasing as HIV-related mortality has declined but the annual number of people newly infected with HIV has not. The international response to contain the HIV pandemic, meanwhile, has grown. Since 2006, an international commitment to scale up prevention, treatment, care and support services in middle and lower-income countries by 2010 has been part of the Universal Access programme, which itself plays an important part in achieving the Millennium Development Goals by 2015. Apart from providing technical support, donor countries and agencies have substantially increased their funding to enable countries to scale up HIV services. Many countries have been developing their HIV monitoring and evaluation systems to generate the strategic information required to track their response and ensure the best use of the new funds. Financial information is an important aspect of the strategic information required for scaling up existing services as well as assessing the effect of new ones. It involves two components: tracking the money available and spent on HIV at all levels, through budget tracking, national health accounts and national AIDS spending assessments, and estimating the cost and efficiency of HIV services. The cost of service provision should be monitored over time, whereas evaluations of the cost-effectiveness of services are required periodically; both should be part of any country’s HIV monitoring and evaluation system. This paper provides country examples of the complementary relationship between monitoring the cost of HIV services and evaluating their cost-effectiveness. It also summarizes global initiatives that enable countries to develop their own HIV monitoring and evaluation systems and to generate relevant, robust and up-to-date strategic information.

Editors’ note: If you have been lost in the jargon, this paper sorts out the differences between effectiveness (outcome or impact of programmes or services), efficiency (resources require to achieve a certain outcome or impact), equity (who benefits from programmes or services), and acceptability (both to users and providers of services and in terms of improvements in the quality of life that programmes achieve). These criteria are supported by other pieces of strategic information that underpin a plan of action for programmes or services, such as direct and indirect costs and HIV incidence/prevalence. Topping this off with a robust monitoring and evaluation system, similar to those that many countries are now developing, can enhance country responses.

Cáceres CF, Aggleton P, Galea JT. Sexual diversity, social inclusion and HIV/AIDS. AIDS. 2008 Aug;22 Suppl 2:S45-55.

Despite a number of programmes to prevent HIV among men who have sex with men (MSM) and, more generally, sexually diverse populations, gay and other homosexually active men continue to be at heightened risk of HIV and its consequences. This paper analyses some of the reasons for this situation and offers policy and programmatic recommendations to contribute to a solution. The social exclusion of MSM and transgender individuals is an overwhelming reality in the majority of countries worldwide. Although progress has been achieved in some countries, in most of the world the situation remains problematic. Present challenges to equality and to the realization of health, include the membership of groups or subcultures with high HIV prevalence, lower quality and coverage of services and programmes and the impact of higher-level influences such as laws, public policies, social norms and culture, which together configure an environment that is hostile to the integration and needs of certain groups. A social inclusion perspective on HIV prevention and AIDS-related care implies the adoption of strategies to understand and confront social vulnerability. Sexual exclusion intensifies the burden of HIV transmission and morbidity. As part of a comprehensive response there is an urgent need to: (i) improve our understanding of the characteristics and HIV burden among sexually diverse populations; (ii) creatively confront legal, social and cultural factors enhancing sexual exclusion; (iii) ensure the provision of broad-based and effective HIV prevention; (iv) offer adequate care and treatment; and (v) confront special challenges that characterize work with these populations in lower and middle-income countries.

Editors’ note: Sexual diversity is a term that questions ‘heteronormativity’, challenging the assumption that there is a single sexual normality and affirming the value of different forms of sexual expression. Sexual behaviour, sexual identity, and gender identify vary significantly across cultures and this complexity argues strongly for participatory prevention programmes – a ‘nothing about us without us’ inclusivity principle that is key to effective programming. Anchoring this approach in commitment to protect and uphold human rights can help overcome the legal, societal, and cultural barriers which create exclusion and undermine HIV programming.