A B S T R AC T Background Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. Methods We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF–FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. Results A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF–FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P = 0.008), and dizziness (15.1% vs. 11.0%, P = 0.03) than the placebo group, but the rates of serious adverse events were similar (P = 0.90). Participants who received TDF–FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF–FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF–FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 personyears, respectively), the efficacy of TDF–FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P = 0.03). Conclusions Daily TDF–FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF–FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.)

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Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

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Sexually Transmitted Infections Treatment Guidelines,2021

Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial Two major vaginal bacterial community types—one dominated by Lactobacillus (592%) and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (408%)—were identified in 688 women profiled Tenofovir reduced HIV incidence by 61% ( P = 0013) in Lactobacillus- dominant women but only 18% ( P = 0644) in women with non- Lactobacillus bacteria, a threefold difference in efficacy Detectible mucosal tenofovir was lower in non- Lactobacillus women, negatively correlating with G vaginalis and other anaerobic bacteria, which depleted tenofovir by metabolism more rapidly than target cells convert to pharmacologically active drug This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism

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Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women

No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop “prevention packages” that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

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Combination HIV prevention: significance, challenges, and opportunities.

Objective To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. Methods To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital. Findings In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million-610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15-49 years. An estimated 3752.0 million people (95% UI: 3555.5 million-3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0-49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region. Conclusion An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV.

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Herpes simplex virus: global infection prevalence and incidence estimates, 2016.

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Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women: Supporting Online Material

BACKGROUND Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2–negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P = 0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P = 0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P = 0.005). CONCLUSIONS In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1410649

Cheryl Baxter

Papers

Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women: Supporting Online Material

Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection

HIV/AIDS in South Africa: Overview of the book

HIV/AIDS in South Africa: New prevention strategies under development and investigation

HIV/AIDS in South Africa: Introduction