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 1) randomly allocated intervention and comparison groups; 2) evaluated interventions to prevent sexual transmission in non-pregnant populations; and 3) 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and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria.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 36 HIV prevention RCTs reporting on 38 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 STI 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.
HIV infection; prevention; microbicide; circumcision; sexually transmitted infections; adherence
The prevalence of sexual violence is increasingly being studied in India. Yet the determinants of sexual violence, irrespective of physical violence, remain largely unexplored. Here the authors identify the determinants of sexual violence, and additionally, explore how the presence of physical violence modifies these determinants. A cross-sectional analysis is conducted using baseline data from a longitudinal study involving young married women attending reproductive health clinics in Southern India. A multivariable logistic regression analysis is conducted to first identify determinants of sexual violence and then repeated after stratifying elements based on presence or absence of physical violence identified from participants’ reports. 36% and 50% of the participants report experiencing sexual and physical violence, respectively. After adjusting for other covariates, women’s partners’ characteristics are found most significantly associated with their odds of experiencing sexual violence. These characteristics include husbands’ primary education, employment as drivers, alcohol consumption, and having multiple sex partners. Women’s contribution to household income also increases their odds of experiencing sexual violence by almost twofold; however, if they are solely responsible for “all” household income, the relationship is found to be protective. Physical violence modifies the determinants of sexual violence, and among women not experiencing physical violence, husbands’ primary education and employment as drivers increase women’s odds of experiencing sexual violence nearly threefold, and women who contribute “all” the household income (n = 62) do not experience sexual violence. These relationships are not significant among women experiencing physical violence. Study findings improve the understanding of the determinants of sexual violence. Future research is needed to examine the risk factors for different types of GBV independently and to tease apart the differences in risk factors depending on women’s experiences. The significance of male partners’ characteristics warrants in-depth research, and in order to promote gender-equitable norms, future interventions need to focus on male behaviors and men’s day-to-day survival challenges, all of which likely influence conflicts in marital relationships.
gender-based violence; sexual violence; physical violence; India
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.
Although women occupy a central position in agriculture in many developing countries, they face numerous constraints to achieving their full potential including unequal access to assets and limited decision-making authority. We explore the intersection of agricultural livelihoods, food and economic security, and women’s sexual and reproductive health in Iringa Region, Tanzania. Our goal was to understand whether the benefits of supporting women in the agricultural sector might also extend to more distal outcomes, including sexual and reproductive health.
Using the Sustainable Livelihoods Framework to guide data collection, we conducted 13 focus group discussions (FGD) with female (n = 11) and male farmers (n = 2) and 20 in-depth interviews with agricultural extension officers (n = 10) and village agro-dealers (n = 10).
Despite providing the majority of agricultural labor, women have limited control over land and earned income and have little bargaining power. In response to these constraints, women adopt adaptive livelihood strategies, such as alcohol production, that allow them to retain control over income and support their households. However, women’s central role in alcohol production, in concert with the ubiquitous nature of alcohol consumption, places them at risk by enhancing their vulnerability to unsafe or transactional sex. This represents a dangerous confluence of risk for female farmers, in which alcohol plays an important role in income generation and also facilitates high-risk sexual behavior.
Alcohol production and consumption has the potential to both directly and indirectly place women at risk for undesirable sexual and reproductive health outcomes. Group formation, better access to finance, and engaging with agricultural extension officers were identified as potential interventions for supporting women farmers and challenging harmful gender norms. In addition, joint, multi-sectoral approaches from health and agriculture and alternative income-generating strategies for women might better address the complexities of achieving safe and sustainable livelihoods for women in this context.
Background. Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial. Methods. We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women with BV (score 7–10) were compared to those with intermediate (score 4–6) and normal flora (score 0–3). During quarterly follow-up visits over 12–24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup. Results. 528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR = 0.4, 95% CI 0.29–.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52–1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65–2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5–16%) were reported using anything else but water to cleanse the vagina over the course of the trial. Conclusions. Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.
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.
Background. Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV).
Methods. One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes.
Results. We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models.
Conclusions. These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition.
Using data from a prospective cohort of 555 adolescent girls and boys from a predominantly Latino neighborhood of San Francisco, we examined how well four survey questionnaire items measuring pregnancy intentions predicted the incidence of pregnancy. We also compared consistency of responses among items and assessed how intentions fluctuated over time. Girls experienced 72 pregnancies over two years (six-month cumulative incidence = 8 percent), and boys reported being responsible for 50 pregnancies (six-month cumulative incidence = 10 percent). Although the probability of becoming pregnant generally increased with higher intention to do so, the risk of becoming pregnant was elevated only at the highest response categories for each item. Most pregnancies occurred among teenagers reporting the lowest levels of intention: for instance, 73 percent of pregnancies occurred among girls who reported that they definitely did not want to become pregnant. Considerable change in respondents’ intentions were found over short periods of time: 18 percent and 41 percent of responses to the wantedness and happiness items, respectively, changed between six-month survey visits. The development of appropriate strategies to reduce pregnancy among adolescents would benefit from a more nuanced understanding of how teenagers view the prospect of pregnancy and what determines whether they actively protect themselves from unintended pregnancy.
The province of KwaZulu-Natal has the highest prevalence of HIV in South Africa, particularly among young women. In order to more closely examine the HIV prevalence and incidence in non-pregnant women from rural, semi-rural and urban areas, data from 5,753 women screened for enrolment into three HIV prevention studies were combined and analysed. The prevalence of HIV infection was 43% at screening. HIV incidence among the 2,523 enrolled HIV-negative women was determined every quarter, and sexual behaviour and socio-demographic data were collected as per respective protocols. During follow-up, 211 women seroconverted (6.6/100 women years). Multivariate analysis found that seroconversion rates were highest among women who were ≤24 years old, single and not cohabiting, and who had incident sexually transmitted infections. The epidemic in KwaZulu-Natal calls for targeted HIV prevention interventions among those at highest risk of acquiring or transmitting infection.
HIV; Women; Cohabitation; Risk factors; South Africa
The extent to which pregnancy intentions mediate the relationship between individual, familial and cultural characteristics and adolescent pregnancy is not well understood. The role of intentions may be particularly important among Latina teenagers, whose attitudes toward pregnancy are more favorable than those of other groups and whose pregnancy rates are high.
Prospective, time-varying data from 2001–2004 were used to investigate whether two measures of pregnancy intentions, wantedness and happiness, mediated associations between risk factors and pregnancy among 213 Latina adolescents in San Francisco. Participants were tested for pregnancy and interviewed about pregnancy intentions, partnerships, family characteristics and activities every six months for two years. Associations and mediation were examined using logistic regression.
Neither pregnancy intention variable mediated relationships between participant characteristics and pregnancy. After adjustment for other measures, wantedness was strongly associated with pregnancy (odds ratio, 2.6), while happiness was not. Having a strong family orientation was associated with happiness (3.7) but unrelated to pregnancy. Low sexual relationship power with a main partner was associated with an elevated risk of pregnancy (3.3). If the pregnancy intentions of all participants were changed to definitely not wanting pregnancy, the estimated decline in pregnancy risk would be 16%.
Pregnancy intentions were important not as mediators but rather as independent risk factors for pregnancy. Differences in pregnancy rates between groups of Latinas may be less a function of intentional choice than of situational factors. Interventions and research should focus on identifying and targeting factors that hinder effective contraceptive use among teenagers who want to avoid pregnancy.
Previous papers in this supplement have reviewed the evidence of the effectiveness of alternative HIV prevention methods from randomised controlled trials and other studies. This paper draws together the main conclusions from these reviews. A conceptual framework is presented that maps the proximal and distal determinants of sexual HIV transmission and helps to identify the stages in the causal pathway at which each intervention approach acts. The advances, gaps and challenges emerging from the reviews of individual intervention methods are summarised and cross-cutting themes identified. Approximately 90% of HIV prevention trials have found no effect on HIV incidence and we explore the alternative explanations for the large number of “flat” trials. We conclude that there is no single explanation for these flat results which may be due to interventions that are ineffective or inappropriately targeted or implemented, or to factors related to the design or conduct of trials. We examine the lessons from these flat results and provide recommendations on what should be done differently in future trials. HIV prevention remains of critical importance in an era of expanded delivery of antiretroviral therapy. In future HIV prevention research, it is important that resources are used as efficiently as possible to provide rigorous evidence of the effectiveness of a wider array of complementary prevention tools.
HIV; prevention and control; randomized controlled trials; sub-Saharan Africa
This paper examines the relationship between bridewealth, socio-demographics, and sexual and reproductive practices among a group of women in Harare, Zimbabwe. The study sample was recruited as part of a six-month safety trial of the diaphragm and a microbicide, between August 2004 and April 2005 in Harare, Zimbabwe. Women underwent two screening visits: first, women completed a demographic and behavioral interviewer-administered questionnaire which included questions on bridewealth; at the second visit, women were offered HIV testing and counseling. Our results included: 417 women were married (currently or in the past) and almost half had had bridewealth negotiated as part of the marriage process. In multivariate analyses, women who were married with bridewealth had more years of education (OR 1.17, 95%CI 1.03–1.32), a higher age of coital debut (OR 1.37, 95%CI 1.09–1.71), and increased likelihood of having ever used male condoms (OR 1.54, 95%CI 1.01–2.37) compared with women who had been married without bridewealth. Bridewealth may be a relevant area of traditional culture to further examine in relation to HIV risk, for its potential association with co-factors that can reduce risk of HIV infection among women in Southern Africa.
bridewealth; Zimbabwe; women’s sexual health; HIV/AIDS; reproductive health
The prevalence of physical domestic violence – violence against women perpetrated by husbands – is staggeringly high across the Indian subcontinent. Although gender-based power dynamics are thought to underlie women's vulnerability, relatively little is known about risk and protective factors. This prospective study in southern India examined the association between key economic aspects of gender-based power, namely spousal employment status, and physical domestic violence. In 2005-2006, 744 married women, aged 16-25, residing in low-income communities in Bangalore, India were enrolled in the study. Data were collected at enrolment, 12 and 24 months. Multivariable logistic regression models were used to examine the prospective association between women's employment status, their perceptions of their husband's employment stability, and domestic violence. Women who were unemployed at one visit and began employment by the next visit had an 80% higher odds of violence, as compared to women who maintained their unemployed status. Similarly, women whose husbands had stable employment at one visit and newly had difficulty with employment had 1.7 times the odds of violence, as compared to women whose husbands maintained their stable employment. To our knowledge, this study is the first from a developing country to confirm that changes in spousal employment status are associated with subsequent changes in violence risk. It points to the complex challenges of violence prevention, including the need for interventions among men and gender transformative approaches to promote gender-equitable attitudes, practices and norms among men and women.
India; gender; domestic violence; longitudinal analysis; economic empowerment; intimate partner violence (IPV); employment status
male circumcision; women; Chlamydia trachomatis; Neisseria gonorrhoeae; Trichomonas vaginalis
male circumcision; women; HIV; Zimbabwe; Uganda; misclassification
Enlisting male partner involvement is perceived as an important component of women’s successful uptake of female-initiated HIV prevention methods. We conducted a longitudinal study among a cohort of 955 Zimbabwean women participating in a clinical trial of the effectiveness of a female-initiated HIV prevention method (the diaphragm and lubricant gel) to: (a) describe the extent to which women involved their male partners in the decision to use the study products, and (b) measure the effect perceived male partner support had on their acceptability and consistent use of these methods. Reported levels of male partner involvement in discussions and decisions regarding: joining the study, study activities, the outcome of HIV/STI test results, and product use were very high. In multivariate analyses, regular disclosure of study product use and partner approval for the diaphragm and gel were significantly associated with women’s acceptability and consistent use of the products; an essential component for determining efficacy of investigational prevention methods. These results support the need for more sophisticated measurement of how couples interact to make decisions that impact study participation and investigational product use as well as more rigorous adaptations and evaluations of existing strategies to involve male partners in female-initiated HIV prevention trials.
HIV prevention; Female-initiated methods; Zimbabwe; Male involvement; Adherence; Acceptability; Couples
The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the “gold standard” HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the “direct effects” of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed.
Causal inference; Intention-to-treat; Randomized trials; Time-dependent confounding
Background Despite widespread condom promotion for HIV prevention, prospective measurement of condom use before and after HIV testing is infrequent.
Methods We analysed data from a prospective study of hormonal contraception and HIV acquisition among Zimbabwean and Ugandan women (1999–2004), in which HIV testing and counselling were performed approximately every 3 months. We used zero-inflated negative binomial (ZINB) models to examine the number and proportion of unprotected sex acts, comparing behaviour reported 2–6 months before HIV testing with behaviour reported both 2–6 months (short-term analysis) and 12–16 months (long-term analysis) after HIV testing.
Results Short- and long-term analyses were similar, so we present only long-term findings from 151 HIV-infected and 650 uninfected participants. The proportion of HIV-infected women reporting any unprotected acts in a typical month declined from 74% (pre-infection behaviour) to 56% (12–16 months after HIV diagnosis). In multivariable models, HIV-infected women were twice as likely to report that all sex acts were protected by condoms after diagnosis compared with beforehand [adjusted odds ratio (aOR): 1.99, 95% confidence interval (CI): 1.12–3.53]; uninfected women were somewhat less likely to report that all acts were protected (aOR: 0.82, 95% CI: 0.64–1.04). HIV-infected women also reduced their number of unprotected acts by 38% (95% CI: −16 to −55%). However, their proportion of unprotected acts changed little (7% reduction, 95% CI: −18 to + 6%). Uninfected women reported little change in number or proportion of unprotected acts over the same time period.
Conclusions HIV-infected women reduced the number, but not the proportion, of unprotected acts. HIV-negative women did not increase condom use after testing and counselling, but neither did they decrease condom use, suggesting that testing negative was not interpreted as endorsement of risky behaviour.
Zero-inflated; negative binomial; HIV/AIDS; male condom; risk behaviour; positive prevention; women; Uganda; Zimbabwe; unprotected sex
Vaginal practices may interfere with the use and/or the effectiveness of female-initiated prevention methods. We investigated whether vaginal practices differed by randomization group in a phase III trial of the diaphragm with lubricant gel (MIRA) in Sub-Saharan Africa (n = 4925), and if they were associated with consistent use of study methods. At baseline, vaginal practices were commonly reported: vaginal washing (82.77%), wiping (56.47%) and insertion of dry or absorbent materials (20.58%). All three practices decreased during the trial. However, women in the intervention group were significantly more likely to report washing or wiping during follow-up compared to those in the control group. Additionally, washing, wiping, and insertion, were all independently and inversely associated with consistent diaphragm and gel use and with condom use as well, regardless of study arm. A better understanding of the socio-cultural context in which these practices are embedded could improve educational strategies to address these potentially modifiable behaviors, and may benefit future HIV prevention interventions of vaginal methods.
Vaginal practices; HIV prevention trials; Female-initiated methods; Condoms; Africa
Objective To identify risk factors for HIV infection among young women aged 15–24 years reporting one lifetime partner in South Africa.
Design In 2003, we conducted a nationally representative household survey of sexual behaviour and HIV testing among 11 904 young people aged 15–24 years in South Africa. This analysis focuses on the subset of sexually experienced young women with only one reported lifetime sex partner (n = 1708).
Methods Using the proximate determinants framework and the published literature we identified factors associated with HIV in young women. The associations between these factors and HIV infection were explored in multivariable logistic regression models.
Results Of the young women, 15% reporting one lifetime partner were HIV positive. In multivariable analyses, young women who had not completed high school were more likely to be infected with HIV compared with those that had completed high school (AOR 3.75; 95% CI 1.34–10.46).
Conclusions Young South African women in this population were at high risk of HIV infection despite reporting only having one lifetime partner. Few individual level factors were associated with HIV infection, emphasizing the importance of developing HIV prevention interventions that address structural and partner level risk factors.
HIV; South Africa; women; education; prevention
The acceptability and use of the diaphragm and lubricant gel were assessed as part of a large randomized controlled trial to determine the effectiveness of the methods in women’s HIV acquisition. 2,452 intervention-arm women were enrolled at five Southern African clinics and followed quarterly for 12–24 months. Acceptability and use data were collected by face-to-face interviews at Month 3 and Exit. Participants were “very comfortable” with the physical mechanics of diaphragm use throughout the trial, and approval of the gel consistency, quantity and the applicator was high. At Exit, consistent disclosure of use (AOR 1.97, 95% CI: 1.10–3.55); an overall high diaphragm rating (AOR 1.84, 95% CI: 1.45–2.34) and perception of partner approval (AOR 1.75, 95% CI: 1.35–2.26) were the most significant acceptability factors independently associated with consistent use. Despite being female-initiated, disclosure of use to male partners and his perceived approval of the products were factors significantly associated with their consistent use.
Diaphragm; Lubricant gel; HIV prevention; Zimbabwe; South Africa; Acceptability; Product adherence