Summary Background The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of ...existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies. Methods We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms “hormonal contraception”, “HIV/acquisition”, “injectables”, “progestin”, and “oral contraceptive pills”. We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features. Findings We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio HR 1·40, 95% CI 1·16–1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10–1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I2 51·1%, 95% CI 0–79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection ( I2 54%, 0–88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86–1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88–1·37). Interpretation Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive. Funding None.
Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package ...including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity IOR = 0.83 vs. COR = 0.68, p-0.02, and having their own income IOR = 2.05 vs. COR = 1.67, p = 0.02. Additionally, within the Intervention arm there was a lower risk of transactional sex IOR = 0.64, 95% CI (0.50, 0.83), and a higher likelihood of using a condom with their current partner IOR = 1.79, 95% CI (1.23, 2.62) over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants HR = 0.61, 95% CI (0.37, 1.01), although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes.
ClinicalTrials.gov NCT02034214.
Summary Intensive research efforts for more than two decades have not yet resulted in an HIV vaccine of even moderate effectiveness. However, some progress has been made with other biomedical ...interventions, albeit on the basis of inconsistent levels of evidence. The male condom, if used correctly and consistently, has been proven in observational studies to be very effective in blocking HIV transmission during sexual intercourse; and, in three randomised trials, male circumcision was protective against HIV acquisition among men. Treatment of sexually transmitted infections, a public health intervention in its own right, has had mixed results, depending in part on the epidemic context in which the approach was assessed. Finally, oral and topical antiretroviral compounds are being assessed for their role in reduction of HIV transmission during sexual intercourse. Research on biomedical interventions poses formidable challenges. Difficulties with product adherence and the possibility of sexual disinhibition are important concerns. Biomedical interventions will need to be part of an integrative package that includes biomedical, behavioural, and structural interventions. Assessment of such multicomponent approaches with moderate effects is difficult. Issues to be considered include the nature of control groups and the effect of adherence on the true effectiveness of the intervention.
Prevention of unintended pregnancies among women living with HIV infection is a strategy recommended by the World Health Organization for prevention of mother-to-child transmission of HIV (PMTCT). We ...assessed pregnancy intentions and contraceptive use among HIV-positive and HIV-negative women with a recent pregnancy in Zimbabwe.
We analyzed baseline data from the evaluation of Zimbabwe's Accelerated National PMTCT Program. Eligible women were randomly sampled from the catchment areas of 157 health facilities offering PMTCT services in five provinces. Eligible women were ≥16 years old and mothers of infants (alive or deceased) born 9 to 18 months prior to the interview. Participants were interviewed about their HIV status, intendedness of the birth, and contraceptive use.
Of 8,797 women, the mean age was 26.7 years, 92.8% were married or had a regular sexual partner, and they had an average of 2.7 lifetime births. Overall, 3,090 (35.1%) reported that their births were unintended; of these women, 1,477 (47.8%) and 1,613 (52.2%) were and were not using a contraceptive method prior to learning that they were pregnant, respectively. Twelve percent of women reported that they were HIV-positive at the time of the survey; women who reported that they were HIV-infected were significantly more likely to report that their pregnancy was unintended compared to women who reported that they were HIV-uninfected (44.9% vs. 33.8%, p<0.01). After adjustment for covariates, among women with unintended births, there was no association between self-reported HIV status and lack of contraception use prior to pregnancy.
Unmet need for family planning and contraceptive failure contribute to unintended pregnancies among women in Zimbabwe. Both HIV-infected and HIV-uninfected women reported unintended pregnancies despite intending to avoid or delay pregnancy, highlighting the need for effective contraceptive methods that align with pregnancy intentions.
We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the ...population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.
Intensive research efforts for more than two decades have not yet resulted in an HIV vaccine of even moderate effectiveness. However, some progress has been made with other biomedical interventions, ...albeit on the basis of inconsistent levels of evidence. The male condom, if used correctly and consistently, has been proven in observational studies to be very effective in blocking HIV transmission during sexual intercourse; and, in three randomised trials, male circumcision was protective against HIV acquisition among men. Treatment of sexually transmitted infections, a public health intervention in its own right, has had mixed results, depending in part on the epidemic context in which the approach was assessed. Finally, oral and topical antiretroviral compounds are being assessed for their role in reduction of HIV transmission during sexual intercourse. Research on biomedical interventions poses formidable challenges. Difficulties with product adherence and the possibility of sexual disinhibition are important concerns. Biomedical interventions will need to be part of an integrative package that includes biomedical, behavioural, and structural interventions. Assessment of such multicomponent approaches with moderate effects is difficult. Issues to be considered include the nature of control groups and the effect of adherence on the true effectiveness of the intervention. PUBLICATION ABSTRACT
Few HIV prevention interventions have been evaluated in randomized controlled trials (RCTs). We examined design, implementation, and contextual considerations that may limit detection of a positive ...or adverse effect in HIV prevention trials.
A systematic review of late phase RCTs for prevention of sexual transmission of HIV that randomly allocated intervention and comparison groups; evaluated interventions to prevent sexual transmission in nonpregnant populations; and reported HIV incidence as the primary or secondary outcome.
PubMed/MEDLINE, other electronic databases, and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria. Descriptive, methodological, and contextual factors were abstracted from each trial.
The review included 37 HIV prevention RCTs reporting on 39 unique interventions. Only six RCTs, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence. Five of the six RCTs significantly reduced HIV infection: all three male circumcision trials, one trial of sexually transmitted infection treatment and care, and one vaccine trial. One microbicide trial of nonoxynol-9 gel produced adverse results. Lack of statistical power, poor adherence, and diluted versions of the intervention in comparison groups may have been important issues for the other trials that demonstrated 'flat' results.
Almost 90% of HIV prevention trials had 'flat' results, which may be attributable to trial design and/or implementation. The HIV prevention community must not only examine evidence from significant RCTs, but must also examine flat trials and address design and implementation issues that limit detection of an effect.
We evaluated the effectiveness of short-term cash and food assistance to improve adherence to antiretroviral therapy (ART) and retention in care among people living with HIV in Tanzania.
At three ...clinics, 805 participants were randomized to three groups in a 3 : 3 : 1 ratio, stratified by site : nutrition assessment and counseling (NAC) and cash transfers (∼$11/month, n = 347), NAC and food baskets (n = 345), and NAC-only (comparison group, n = 113, clinicaltrials.gov NCT01957917). Eligible people living with HIV were at least 18 years, initiated ART 90 days or less prior, and food insecure. Cash or food was provided for 6 or less consecutive months, conditional on visit attendance. The primary outcome was medication possession ratio (MPR ≥ 95%) at 6 months. Secondary outcomes were appointment attendance and loss to follow-up (LTFU) at 6 and 12 months.
The primary intent-to-treat analysis included 800 participants. Achievement of MPR ≥ 95% at 6 months was higher in the NAC + cash group compared with NAC-only (85.0 vs. 63.4%), a 21.6 percentage point difference 95% confidence interval (CI): 9.8, 33.4, P < 0.01. MPR ≥ 95% was also significantly higher in the NAC + food group vs. NAC-only (difference = 15.8, 95% CI: 3.8, 27.9, P < 0.01). When directly compared, MPR ≥ 95% was similar in the NAC + cash and NAC + food groups (difference = 5.7, 95% CI: -1.2, 12.7, P = 0.15). Compared with NAC-only, appointment attendance and LTFU were significantly higher in both the NAC + cash and NAC + food groups at 6 months. At 12 months, the effect of NAC + cash, but not NAC + food, on MPR ≥ 95% and retention was sustained.
Short-term conditional cash and food assistance improves ART possession and appointment attendance and reduces LTFU among food-insecure ART initiates in Tanzania.
To determine the prevalence of HIV infection, HIV risk factors, and exposure to national HIV prevention programs, and to identify factors associated with HIV infection among South African youth, aged ...15-24 years.
A cross-sectional, nationally representative, household survey.
From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15-24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth.
Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men, a history of genital ulcers in the past 12 months was associated with HIV infection adjusted odds ratio (AOR), 1.91; 95% confidence interval (CI), 1.04-3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR, 1.75; 95% CI, 1.26-2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women, increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR, 0.60; 95% CI, 0.40-0.89; AOR, 0.61; 95% CI, 0.43-0.85, respectively).
This survey confirms the high HIV prevalence among young people in South Africa and, in particular, young women's disproportionate risk. Programs for youth must continue to promote partner reduction, consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change.
The rigorous evaluation of the impact of combination HIV prevention packages at the population level will be critical for the future of HIV prevention. In this review, we discuss important ...considerations for the design and interpretation of cluster randomized controlled trials (C-RCTs) of combination prevention interventions. We focus on three large C-RCTs that will start soon and are designed to test the hypothesis that combination prevention packages, including expanded access to antiretroviral therapy, can substantially reduce HIV incidence. Using a general framework to integrate mathematical modelling analysis into the design, conduct, and analysis of C-RCTs will complement traditional statistical analyses and strengthen the evaluation of the interventions. Importantly, even with combination interventions, it may be challenging to substantially reduce HIV incidence over the 2- to 3-y duration of a C-RCT, unless interventions are scaled up rapidly and key populations are reached. Thus, we propose the innovative use of mathematical modelling to conduct interim analyses, when interim HIV incidence data are not available, to allow the ongoing trials to be modified or adapted to reduce the likelihood of inconclusive outcomes. The preplanned, interactive use of mathematical models during C-RCTs will also provide a valuable opportunity to validate and refine model projections.
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