The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)

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Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of randomised controlled trials. It was initially published in 1996 and focused on the reporting of parallel group randomised controlled trials. The statement was revised in 2001, with a further update in 2010. A separate CONSORT statement for the reporting of abstracts was published in 2008. In earlier papers we considered the implications of the 2001 version of the CONSORT statement for the reporting of cluster randomised trial. In this paper we provide updated and extended guidance, based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstracts.

https://www.bmj.com/content/bmj/345/bmj.e5661.full.pdf

CONSORT statement: extension to cluster randomised trials

The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

/pdf/effectiveness-and-safety-of-tenofovir-gel-an-antiretroviral-2ccoqcdrry.pdf

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

Objectives: To review the scientific data on the role of sexually transmitted diseases (STDs) in sexual transmission of HIV infection and discuss the implications of these findings for HIV and STD prevention policy and practice Methods: Articles were selected from a review of Medline, accessed with the OVID search engine The search covered articles from January 1987 to September 1998 and yielded 2101 arti- cles Methods used to uncover articles which might have been missed included searching for related articles by author, and combing literature reviews In addition, all abstracts under the cat- egory "sexually transmitted diseases" from the XI and XII International Conferences on AIDS (Vancouver 1996 and Geneva 1998) and other relevant scientific meetings were reviewed Efforts were made to locate journal articles which resulted from the research reported in the identified abstracts All original journal articles and abstracts which met one of the following criteria were included: (1) studies of the biological plausibility or mechanism of facilitation of HIV infectious- ness or susceptibility by STDs, (2) prospective cohort studies (longitudinal or nested case-control) which estimate the risk of HIV infection associated with specific STDs or STD syndromes, or (3) intervention studies which quantitate the eVect which STD treatment can have on HIV incidence Results: Strong evidence indicates that both ulcerative and non-ulcerative STDs promote HIV transmission by augmenting HIV infectiousness and HIV susceptibility via a variety of biological mechanisms These eVects are reflected in the risk estimates found in numerous prospective studies from four continents which range from 20 to 235, with most clustering between 2 and 5 The relative importance of ulcerative and non-ulcerative STDs appears to be complex Owing to the greater frequency of non-ulcerative STDs in many populations, these infections may be responsible for more HIV transmission than genital ulcers However, the limited reciprocal impact of HIV infection on non-ulcerative STDs and the evidence that non-ulcerative STDs may increase risk primarily for the receptive partner (rather than bidirectionally) may modulate the impact of these diseases The results of two community level randomised, controlled intervention trials conducted in Africa suggest that timely provision of STD services can substantially reduce HIV incidence, but raise additional questions about the optimal way to target and implement these services to achieve the greatest eVect on HIV transmission Conclusions: Available data leave little doubt that other STDs facilitate HIV transmission through direct, biological mechanisms and that early STD treatment should be part of a high quality, comprehensive HIV prevention strategy Policy makers, HIV prevention programme managers, and providers should focus initial implementation eVorts on three key areas: (i) improving access to and quality of STD clinical services; (ii) promoting early and eVective STD related healthcare behaviours; and (iii) establishing surveillance systems to monitor STD and HIV trends and their interrelations (Sex Transm Inf 1999;75:3-17)

https://sti.bmj.com/content/sextrans/75/1/3.full.pdf

From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection.

OBJECTIVE:: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND:: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN:: Systematic review and meta-analysis of longitudinal studies. METHODS:: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS:: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS:: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial

OBJECTIVE--To determine risk factors for syphilis and sexually transmitted disease (STD) syndromes, and to study health seeking behaviour among those with STD syndromes, in the population of Mwanza Region, North-Western Tanzania. METHODS--A population-based random cluster sample survey, stratified by rural, roadside or urban residence, of 4173 individuals aged 15-54 years was performed in 1990-91. The seroprevalence of syphilis and the prevalence and incidence of self-reported genital ulcer syndrome (GUS) and genital discharge syndrome (GDS) are reported in the accompanying paper. This paper reports on risk factors for these conditions and on health seeking behaviour among those reporting them. RESULTS--In both sexes, the risk of STDs increased with the reported number of sexual partners in the previous five years. Men who were separated, divorced or widowed were at increased risk of STDs, but this was not the case among women. Higher educational status was associated with an increased risk of urethral discharge in males but with a decreased prevalence of syphilis in females. Male circumcision was associated with an increased risk of urethral discharge but a reduced prevalence of syphilis. Nearly all men, and 90% of women, reporting symptoms of genital discharge or ulceration had sought treatment. Of these, approximately 70% of males and 60% of females had sought treatment in the official health sector. CONCLUSIONS--Targetted health education concerning risk reduction for HIV infection and other STDs should be a high priority in this population. Improved case management of STDs in health centres and dispensaries may have a substantial impact on the incidence of these infections.

https://sti.bmj.com/content/sextrans/69/6/421.full.pdf

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour

J. Newell

Papers

Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial

A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour