Introduction Antiretroviral pre-exposure prophylaxis (PrEP) reduces the incidence of acquisition of human immunodeficiency virus type 1 (HIV-1) in men who have sex with men and is a promising approach for preventing HIV-1 in heterosexual populations. Methods We conducted a randomized, three-arm trial of oral antiretroviral PrEP among heterosexual couples from Kenya and Uganda in which one member was HIV-1 seronegative and the other HIV-1 seropositive. Seronegative partners were randomly assigned to once-daily tenofovir (TDF), combination emtricitabine/tenofovir (FTC/TDF), or matching placebo and followed monthly for up to 36 months. At enrollment, HIV-1 seropositive partners were not eligible for antiretroviral therapy under national guidelines. All couples received standard HIV-1 treatment and prevention services, including individual and couples risk-reduction counseling and condoms. Results 4758 couples were enrolled; for 62%, the HIV-1 seronegative partner was male. For HIV-1 seropositive participants, the median CD4 count was 495 cells/μL (interquartile range 375–662). Of 82 post-randomization HIV-1 infections, 17 were among those assigned TDF (incidence 0.65 per 100 person-years), 13 among those assigned FTC/TDF (incidence 0.50 per 100 person-years), and 52 among those assigned placebo (incidence 1.99 per 100 person-years), indicating a 67% relative reduction in HIV-1 incidence for TDF (95% CI 44 to 81, p<0.001) and 75% for FTC/TDF (95% CI 55 to 87, p<0.001). HIV-1 protective effects of FTC/TDF and TDF were not significantly different (p=0.23), and both study medications significantly reduced HIV-1 incidence in both men and women. The rate of serious medical events was similar across the study arms. Conclusions Oral TDF and FTC/TDF provided substantial protection against HIV-1 acquisition in heterosexual men and women, with comparable efficacy of TDF and FTC/TDF. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number NCT00557245)

BACKGROUND 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. METHODS 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, ≥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. RESULTS 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 log10 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. CONCLUSIONS Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log10 copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

This study evaluated estimates of depression symptoms, major depression, alcohol use or disorders and their association with ART adherence in sub-Saharan Africa. Studies published between January 1, 2006 and July 31, 2011 that documented rates of these mental health problems were identified through electronic databases. A pooled analysis of 23 studies reporting rates of depression symptoms and six studies reporting rates of major depression indicated a pooled estimate of 31.2% (95% CI 25.5-38.2%, Tau(2) = 0.23) and 18% (95% CI 12.3-25.8%, Tau(2) = 0.19) respectively. Few studies reported rates of alcohol use or disorders, and so we did not pool their estimates. Likelihood of achieving good adherence was 55% lower among those with depression symptoms compared to those without (pooled OR = 0.45 (95% CI 0.31-0.66, Tau(2) = 0.20, P value = 0.000). Interventions to improve mental health of HIV-positive individuals and to support adherence are desperately needed in sub-Saharan Africa.

Although more than 25 million people in sub‐Saharan Africa have human immunodeficiency virus (HIV) infection, little is known regarding their cancer risk. We investigated cancer risk among persons with HIV/AIDS in Uganda using record‐linkage. We linked records of 12,607 HIV‐infected persons attending The AIDS Support Organization (TASO) in Kyadondo County from October 1988 through December 2002 to the Kampala Cancer Registry. We calculated standardized incidence ratios (SIRs) to identify increased cancer risks in the early (4–27 months after TASO registration), late (28–60 months), or combined (4–60 months) incidence periods. We identified 378 cancers (181 prevalent, 197 incident) among TASO participants. Of incident cancers, 137 (70%) were AIDS‐defining cancers. Risk was increased in the early‐incident period, compared to the general population, for the AIDS‐defining cancers: Kaposi sarcoma (SIR 6.4, 95%CI 4.8–8.4), non‐Hodgkin lymphoma (6.7, 1.8–17), and cervical carcinoma (2.4, 1.1–4.4). These three cancers were also increased in the combined periods. Risks of five non‐AIDS‐defining cancers were increased in the combined periods: Hodgkin lymphoma (5.7, 1.2–17) and cancers of the conjunctiva (SIR 4.0; 1.5–8.7), kidney (16, 1.8–58), thyroid (5.7, 1.1–16), and uterus (5.5, 1.5–14). Cancers of the breast, nasopharynx, and lung were increased either in the early or late incident periods only. Among 407 children, seven cancers were observed, of which five were Kaposi sarcoma. The application of a record‐linkage design in Africa broadens the repertoire of epidemiological tools for studying HIV‐infected populations. We confirm the increased risks of AIDS‐defining cancers and report increased risks of a few non‐AIDS‐defining cancers. © 2005 Wiley‐Liss, Inc.

Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial. Please see later in the article for the Editors' Summary