Summary Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 ...acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. Methods In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Findings Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 IQR 12·6–24·2 months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 IQR 12·8–24·2 months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Interpretation Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. Funding US National Institutes of Health and the Bill & Melinda Gates Foundation.
Summary Background Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. ...We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms. Methods For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56 683) by cross-sectional random surveys of community residents aged 18–32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. This trial is registered at ClinicalTrials.gov , number NCT00203749. Findings The estimated incidence of HIV in the intervention group was 1·52% versus 1·81% in the control group with an estimated reduction in HIV incidence of 13·9% (relative risk RR 0·86, 95% CI 0·73–1·02; p=0·082). HIV incidence was significantly reduced in women older than 24 years (RR=0·70, 0·54–0·90; p=0·0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12–39; p=0·0003), by 45% (25–69; p<0·0001) in men and 15% (3–28; p=0·013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3–9) in communities in the intervention group. Interpretation These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level. Funding US National Institute of Mental Health, the Division of AIDS of the US National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research of the US National Institutes of Health.
Summary Background Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals ...using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour. Methods We undertook a longitudinal analysis of data from the Partners PrEP Study, a double-blind, randomised, placebo-controlled trial of daily oral pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-serodiscordant couples (n=3163, ≥18 years of age). Efficacy for HIV prevention was publicly reported in July 2011, and participants continued monthly follow-up thereafter. We used regression analyses to compare the frequency of sex—unprotected by a condom—during the 12 months after compared with the 12 months before July 2011, to assess whether knowledge of pre-exposure prophylaxis efficacy for HIV prevention caused increased sexual risk behaviour. Results We analysed 56 132 person-months from 3024 HIV-uninfected individuals (64% male). The average frequency of unprotected sex with the HIV-infected study partner was 59 per 100 person-months before unmasking versus 53 after unmasking; we recorded no immediate change (p=0·66) or change over time (p=0·25) after July, 2011. We identified a significant increase in unprotected sex with outside partners after July, 2011, but the effect was small (average of 6·8 unprotected sex acts per year vs 6·2 acts in a predicted counterfactual scenario had patients remained masked, p=0·04). Compared with before July, 2011, we noted no significant increase in incident sexually transmitted infections or pregnancy after July, 2011. Interpretation Pre-exposure prophylaxis, provided as part of a comprehensive prevention package, might not result in substantial changes in risk-taking sexual behaviour by heterosexual couples. Funding The Bill & Melinda Gates Foundation and the US National Institute of Mental Health.
Swaziland has the highest national HIV prevalence worldwide. The Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national HIV incidence estimate based on prospectively observed ...HIV seroconversions.
A two-stage survey sampling design was used to select a nationally representative sample of men and women aged 18-49 years from 14 891 households in 575 enumeration areas in Swaziland, who underwent household-based counselling and rapid HIV testing during 2011. All individuals aged 18-49 years who resided or had slept in the household the night before and were willing to undergo home-based HIV testing, answer demographic and behavioural questions in English or siSwati, and provide written informed consent were eligible for the study. We performed rapid HIV testing and assessed sociodemographic and behavioural characteristics with use of a questionnaire at baseline and, for HIV-seronegative individuals, 6 months later. We calculated HIV incidence with Poisson regression modelling as events per person-years × 100, and we assessed covariables as predictors with Cox proportional hazards modelling. Survey weighting was applied and all models used survey sampling methods.
Between Dec 10, 2010, and June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232 (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting in a weighted HIV incidence of 2·4% (95% CI 2·1-2·8). Incidence was nearly twice as high in women (3·1%; 95% CI 2·6-3·7) as in men (1·7%; 1·3-2·1, p<0·0001). Among men, partner's HIV-positive status (adjusted hazard ratio aHR 2·67, 1·06-6·82, p=0·040) or unknown serostatus (aHR 4·64, 2·32-9·27, p<0·0001) in the past 6 months predicted HIV seroconversion. Among women, significant predictors included not being married (aHR 2·90, 1·44-5·84, p=0·0030), having a spouse who lives elsewhere (aHR 2·66, 1·29-5·45, p=0·0078), and having a partner in the past 6 months with unknown HIV status (aHR 2·87, 1·44-5·84, p=0·0030).
Swaziland has the highest national HIV incidence in the world. In high-prevalence countries, population-based incidence measures and programmes that further expand HIV testing and support disclosure of HIV status are needed.
President's Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and Prevention.
Summary Background Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to ...be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP. Methods We did a randomised, double-blind, placebo-controlled three-group phase 3 trial of daily oral tenofovir disoproxil fumarate and emtricitabine plus tenofovir disoproxil fumarate PrEP in HIV-1 uninfected individuals in heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial's placebo group was discontinued and thereafter the active groups were continued, and participants initially randomly assigned to placebo were offered rerandomisation in a 1:1 ratio to tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate as PrEP. The primary endpoints were HIV-1 seroconversion and safety. This trial is registered with ClinicalTrials.gov , number NCT00557245. Findings 4410 (99·6%) of 4427 couples received tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate and were followed up for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 occurred in individuals assigned tenofovir disoproxil fumarate (incidence 0·71 cases per 100 person-years) and 21 were in those assigned emtricitabine plus tenofovir disoproxil fumarate (0·48 cases per 100 person-years); HIV-1 incidence in the placebo group until discontinuation was two cases per 100 person-years. HIV-1 prevention efficacy with emtricitabine plus tenofovir disoproxil fumarate was not significantly different from that of tenofovir disoproxil fumarate alone (hazard ratio HR 0·67, 95% CI 0·39–1·17; p=0·16). Detection of tenofovir in plasma samples, compared with no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the tenofovir disoproxil fumarate group (HR 0·15, 95% CI 0·06–0·37; p<0·0001) and 93% for the emtricitabine plus tenofovir disoproxil fumarate group (0·07, 0·02–0·23; p<0·0001). No significant differences were noted in the frequency of deaths, serious adverse events, or serum creatinine and phosphorus abnormalities between the two groups. Interpretation These results do not rule out the potential for a slight difference in HIV-1 protection with tenofovir disoproxil fumarate compared with emtricitabine plus tenofovir disoproxil fumarate, but show that once-daily oral tenofovir disoproxil fumarate or emtricitabine plus tenofovir disoproxil fumarate regimens both provide high protection against HIV-1 acquisition in heterosexual men and women. Funding Bill & Melinda Gates Foundation and US National Institutes of Health.
As part of the HPTN 065 study in the Bronx, New York and Washington, the authors, we surveyed clinicians to assess for shifts in their practices and attitudes around HIV treatment and prevention. ...Antiretroviral therapy (ART)-prescribing clinicians at 39 HIV care sites were offered an anonymous Web-based survey at baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and 141 respondents at follow-up had similar characteristics-almost 60% were female, median age was 47 years, two-thirds were physicians, and nearly 80% were HIV specialists. The percentage who reported recommending ART irrespective of CD4 count was higher at follow-up (15% versus 68%), as was the percentage who would initiate ART earlier for patients having unprotected sex with partners of unknown HIV status (64% versus 82%), and for those in HIV-discordant partnerships (75% versus 87%). In line with changing HIV treatment guidelines during 2010 to 2013, clinicians increasingly supported early ART for treatment and prevention.
Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated ...in public HIV care clinics in Kenya.
As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010.
After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25–39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2–39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation.
We observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible.
National Institute of Mental Health and Bill & Melinda Gates Foundation.
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