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      Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women

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      Massachusetts Medical Society

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          Abstract

          New England Journal of Medicine, 367(5), 399-410

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          New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data.

          Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001-02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55.1% to 92.7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60.3% to 94.2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35.7% to 60.3% of heterosexually transmitted HIV infections that would otherwise occur. Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.
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            Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.

            Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1. We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses. A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed. Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.) 2010 Massachusetts Medical Society
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              What's love got to do with it? Explaining adherence to oral antiretroviral pre-exposure prophylaxis for HIV-serodiscordant couples.

              Adherence may be the "Achilles heel" of pre-exposure prophylaxis (PrEP), a promising biomedical approach to HIV prevention. This article presents an explanation of PrEP adherence for African serodiscordant couples derived from qualitative data. Explaining quantitative findings is one way qualitative investigation contributes to research in medicine and public health. This qualitative interview study was nested in the Partners PrEP Study, a phase III randomized trial evaluating oral tenofovir and emtricitabine/tenofovir PrEP to prevent HIV acquisition by HIV-uninfected partners in serodiscordant heterosexual couples. In-depth qualitative interviews were provided by 60 Partners PrEP Study participants in Uganda. Interviews used open-ended questions eliciting information on adherence experiences, barriers, and facilitators. An inductive approach informed by grounded theory methodology was used to analyze study data. The proposed explanation may be summarized as follows. Serodiscordance destabilizes couples, as the HIV-negative partner reacts with anger, fear, and sadness to the implication of infidelity represented by HIV infection. A "discordance dilemma" ensues, as the desire to avoid acquiring HIV and the advantages of preserving the relationship become competing priorities. PrEP is seen as a solution-a means of safeguarding health without ending the relationship. PrEP users benefit from the support of partners, who reinforce adherence. Where discord in the relationship persists, adherence suffers. PrEP adherence in serodiscordant couples may be understood as a function of the desire to reduce risk although preserving a partnered relationship. PrEP use in stable couples may be associated with improved adherence and thus, greater effectiveness.
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                Author and article information

                Journal
                Massachusetts Medical Society
                2012
                02 August 2012
                20 June 2017
                Article
                10.1056/NEJMOA1108524
                3770474
                22784037
                54e90db9-0644-47a4-af56-032c9e41d051
                History

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