[Show abstract][Hide abstract] ABSTRACT: Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular.
[Show abstract][Hide abstract] ABSTRACT: In VOICE, a multisite HIV pre-exposure prophylaxis (PrEP) trial, plasma drug levels pointed to widespread product nonuse, despite high adherence estimated by self-reports and clinic product counts. Using a socio-ecological framework (SEF), we explored socio-cultural and contextual factors that influenced participants' experience of daily vaginal gel and oral tablet regimens in VOICE.
In Johannesburg, a qualitative ancillary study was concurrently conducted among randomly selected VOICE participants assigned to in-depth interviews (n = 41), serial ethnographic interviews (n = 21), or focus group discussions (n = 40). Audiotaped interviews were transcribed, translated, and coded thematically for analysis.
Of the 102 participants, the mean age was 27 years, and 96% had a primary sex partner with whom 43% cohabitated. Few women reported lasting nonuse, which they typically attributed to missed visits, lack of product replenishments, and family-related travel or work. Women acknowledged occasionally skipping or mistiming doses because they forgot, were busy, felt lazy or bored, feared or experienced side effects. However, nearly all knew or heard of other study participants who did not use products daily. Three overarching themes emerged from further analyses: ambivalence toward research, preserving a healthy status, and managing social relationships. These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products. The unknown efficacy of products, their connection with HIV infection, challenges with daily regimen given social risks, lack of support-from partners and significant others-and the relationship tradeoffs entailed by using the products appear to discourage adequate product use.
Personal acknowledgment of product nonuse was challenging. This qualitative inquiry highlighted key influences at all SEF levels that shaped women's perceptions of trial participation and experiences with investigational products. Whether these impacted women's behaviors and may have contributed to ineffective trial results warrants further investigation.
PLoS ONE 01/2014; 9(2):e89118. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intimate partner violence and condom and diaphragm nonadherence among women in an HIV prevention trial in southern Africa.
Kacanek D, Bostrom A, Montgomery ET, Ramjee G, de Bruyn G, Blanchard K, Rock A, Mtetwa S, van der Straten A; MIRA Team.
• *Department of Biostatistics, Harvard School of Public Health, Boston, MA; †Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ‡RTI International, Women's Global Health Imperative, San Francisco, CA; §HIV Prevention Unit of the South African Medical Research Council, Durban, South Africa; ‖Sanofi Pasteur, Swiftwater, PA; ¶Ibis Reproductive Health, Cambridge, MA; #JSI Research and Training Institute, Washington, DC; **University of Zimbabwe, Harare, Zimbabwe; and ††Department of Medicine, Center for AIDS Prevention Studies, University of California San Francisco, San Francisco, CA.
We longitudinally examined the effect of intimate partner violence (IPV) on condom and diaphragm nonadherence among women in the Methods for Improving Reproductive Health in Africa study, a phase III HIV prevention trial in southern Africa.
Recent IPV (fear of violence, emotional abuse, physical violence, or forced sex, in past 3 months), condom nonadherence, and diaphragm nonadherence were assessed at baseline, 12 month, and exit visits (up to 24 months). The association between IPV and (1) condom nonadherence or (2) diaphragm nonadherence across visits was modeled using Generalized Estimating Equations adjusting for potential confounders.
Of 4505 participants, 55% reported recent IPV during their trial participation. Women reported fearing violence (41%), emotional abuse (38%), being physically assaulted (16%), and forced sex (15%) by their regular male partner. IPV was associated with condom nonadherence in both study arms [adjusted odds ratio (AOR): 1.41, 95% confidence interval (CI): 1.24 to 1.61 (control arm) and AOR: 1.47, 95% CI: 1.28 to 1.69, (intervention arm)] and with diaphragm nonadherence (AOR 1.24, 95% CI: 1.06 to 1.45) adjusting for age, study sites, number of sex partners, and knowledge of male partner infidelity. Modeling effects of each form of IPV separately on nonadherence outcomes yielded similar results.
Prevalence of recent IPV was high and associated with condom and diaphragm nonadherence during the trial. Counseling in prevention trials should proactively address IPV, for its own sake, and in product and risk-reduction counseling. Strategies to encourage men's positive involvement in product use and prevent IPV perpetration should be considered.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE:: To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe. DESIGN:: Secondary data analysis of 4913 sexually active women aged 18-49 years followed for up to 24 months in the Methods for Improving Reproductive Health in Africa (MIRA) phase III effectiveness trial of the diaphragm and lubricant gel for HIV prevention. METHODS:: Participants were interviewed quarterly about contraception and sexual behavior and were tested for pregnancy, HIV, and other sexually transmitted infections. We used a Cox proportional hazards marginal structural model, weighted by the inverse probability of hormonal contraception use, to compare the risk of HIV acquisition among nonpregnant women reporting use of combined oral contraceptive pills (COC), progestin-only pills (POP), and/or injectable hormonal contraception to women not using these methods. RESULTS:: During the study, 283 participants seroconverted. Use of oral contraceptives (POP or COC) was not associated with HIV risk [adjusted hazard ratio (HRa) = 0.86, 95% confidence interval (CI) 0.32, 1.78]. Injectable hormonal contraception was associated with a small nonsignificant risk of HIV infection (HRa = 1.34, 95% CI 0.75, 2.37). The effect of injectable hormonal contraception was similar in the unweighted site-adjusted only (HRa = 1.32, 95% CI 1.00, 1.74) and baseline factor adjusted models (HRa = 1.27, 95% CI 0.94, 1.72). CONCLUSIONS:: In this study, oral contraceptives were not associated with HIV acquisition. There is substantial uncertainty in the effect of injectable hormonal contraception on HIV risk. These findings underscore the importance of dual protection with condoms and the need for diverse contraceptive options for women at risk of HIV infection.
AIDS (London, England) 03/2013; 27(6):1001-1009. · 4.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interpretation of microbicide trial results has been compromised by challenges to accurate measurement of product adherence and sexual risk behaviors. This article provides an evaluation of the methods used to measure adherence and other sensitive behaviors relevant to assessment of product safety and effectiveness in recently completed trials of vaginal and rectal microbicides. We review the strengths and limitations of existing and novel behavioral measurement strategies and provide recommendations for future trial design with the goal of facilitating the development and identification of safe and effective microbicides for HIV prevention.
[Show abstract][Hide abstract] ABSTRACT: The Wisebag™, a lunchbag-style container with an electronic events-monitoring system, was designed as a real-time indirect objective measure of microbicide gel use. Due to cost, alternative functionalities (i.e. use of offline and dummy versions) were explored. We conducted a three-arm, double-blinded pilot study among 50 HIV-negative women in Durban, South Africa to assess participant adherence and Wisebag acceptability and performance. Participants were randomized 2:2:1 to Wisebag with online (events transmitted via cellular signal in real-time), offline (events stored in device memory) or inactive "dummy" devices. Participants were instructed to open the Wisebag daily for 2 weeks, retrieve a study sticker and affix it on a diary card. All participants completed the study. At exit, 94 % did not know which device they had received, nor could they differentiate the Wisebag types when presented with the three options. Five offline devices failed (no data recorded). Per Wisebag events, 26 % of women were perfectly adherent compared to 48 % by self-report and 46 % per diary card. Of reported non-adherence, 92 % did not open the Wisebag (travelling or forgot) and 22 % opened Wisebag >1×/day (curiosity). Participants liked and were comfortable carrying Wisebag. Successful blinding will allow inclusion of offline and/or dummy Wisebags in future study designs. Perfect adherence by opening events was significantly lower than by self-report, highlighting the importance of objective measures of adherence in clinical trials. Additional studies to validate Wisebag data with actual products, with and without SMS and online functionality, in different populations and settings, and in comparison to biomarkers are warranted.
[Show abstract][Hide abstract] ABSTRACT: Dried blood spots (DBS) are widely used to test for HIV in a variety of research and service delivery settings; however, uniform guidelines regarding collection, storage and DNA extraction processes have neither been developed nor evaluated. Previously published reports suggested DBS may be stored at room temperature for up to 60 days, and intensive stability tests have shown that DBS can withstand high temperatures, humidity and freeze-thawing. During the implementation of a large randomized controlled trial (RCT) in southern Africa, with HIV acquisition as the primary endpoint, we observed 65 instances when DBS samples collected from the same day as a positive HIV antibody test yielded negative DNA polymerase chain reaction (PCR) results. The source of this discrepancy may have been due to inadequate specimen volume, filter paper or DNA extraction procedures, but were most likely due to storage conditions that have been reported as acceptable in other settings.
International Journal of STD & AIDS 09/2012; 23(9):649-52. · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In sub-Saharan Africa, HIV incidence and prevalence remain disproportionately high among women. Vaginal rings (VRs) have been formulated for the delivery of antiretroviral-based microbicides, and their favorable safety and tolerability profiles reported in clinical studies. Although the concept of drug release through a VR has existed since 1970, and VRs have been marketed since 1992 for contraceptive or hormone replacement purposes, VR use as a microbicide delivery system is a novel application. This is the first study to evaluate VR adherence among African women in the context of its potential use as an HIV prevention method, to examine predictors of adherence, and to describe clinical or contextual reasons for VR removals or nonadherence. This was a randomized trial of the safety and acceptability of a placebo VR worn for 12 weeks in 170 HIV-negative, African women aged 18-35 in four clinic sites in South Africa and Tanzania. The findings suggest that adherence to VR use in the context of HIV prevention trials in these communities should be high, thereby enabling more accurate assessment of an active microbicide safety and efficacy.
AIDS and Behavior 07/2012; 16(7):1787-98. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Duet(®) is a microbicide-delivery system and cervical barrier for use daily or precoitally. We conducted a crossover study among 80 Zimbabwean women to explore factors associated with use-regimen preference. Women were assigned in random order to 14 days of precoital and 14 days of daily Duet and BufferGel use. About 51 % of women preferred precoital use, 39 % preferred daily use, and 10 % liked both equally. Overall product adherence during sex was similar for both use-regimens. In multivariable analysis, diaphragm experience was associated with preference for precoital use (AOR 2.80, 95 % CI 1.01-7.76). Reasons for preferring precoital use included use only when needed, cleanliness, and discomfort with daily use. Daily use preference included convenience, discreetness, and being prepared for "sex-on-demand." Different personal and life circumstances may result in varying use-regimen preferences. Methods that can accommodate both coitally-related and daily use may be advantageous by providing more choice to users.
AIDS and Behavior 07/2012; 16(7):1799-1807. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Male and female gender roles and inequalities are important in contributing to the disproportionate burden of HIV experienced by women in sub-Saharan Africa. Within the context of an HIV prevention trial, we aimed to describe and understand male partner influence on women's use of HIV-prevention methods. Our presumption was not that regressive gender norms prevailed - rather, that a wide range of gendered attitudes and dynamics would be expressed among couples. Data from 16 focus groups with Zimbabwean female trial participants and their male partners and 4 in-depth couples interviews were collected, and form the basis of the analysis. Findings offer descriptions of how couples have adapted techniques for negotiating modern household economies and sexual decision-making in a manner that both preserves traditional gender roles, while accommodating women's entrance into new domains such as the workforce or an HIV-prevention trial. Women's agency to introduce novel female-initiated-method use into her intimate relationships is described. Men and women's accounts of method introduction and use suggest different perceptions about the locus of sexual decision making. The study provides unique insight into a gendered context that is dynamic yet sensitive to change, which in turn can provide useful information to more appropriately guide HIV-prevention activities in this setting.
Culture Health & Sexuality 07/2012; 14(7):795-810. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaginal rings (VRs) are new methods for continuous delivery of microbicides. This is the first study to quantitatively and qualitatively explore the acceptability of rings in Africa: 157 HIV-negative, sexually active women aged 18-35 used a placebo silicone elastomer ring for 12 weeks. They completed product acceptability questionnaires every 4 weeks. We conducted 6 exit focus group discussions with a subset of 48 women and 19 in-depth interviews with male partners. Retention in the study was high (97 %). Initial insertion at the clinic was successful on first attempt for 81 % of participants. Most women were comfortable using the ring, and very few (≤2 %) could feel it during daily activities or had ring-related physical or emotional problems. In the qualitative interviews many participants reported that they initially had concerns about using the ring. However, only a minority of women actually reported concerns with the ring during the study. The most frequent concern was that the ring would get lost inside the body (20 %), and this was significantly correlated with study site, frequently thinking about the ring and reporting that the ring was not very easy to remove. Qualitative data suggest that informants grew to like the ring because it felt securely placed, was unnoticeable during daily activities, and felt "normal" during sex. The ring appeared to be highly acceptable for women and men. Initial concerns with this novel method suggest a need for enhanced product counseling when VRs are introduced.
AIDS and Behavior 05/2012; 16(7):1775-86. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Consistent condom use and the substitution of condoms with potential HIV prevention methods of lower or unknown effectiveness are important concerns in the development of new prevention technologies. This qualitative study explored obstacles to consistent condom use with the diaphragm in MIRA, an HIV prevention trial in South Africa and Zimbabwe. We conducted 26 focus group discussions (FGDs) with 206 women and 7 FGDs and 10 in-depth interviews with 41 male partners of intervention-arm women. The belief that the diaphragm/gel prevented HIV, women's difficulties negotiating condom use, and men's unawareness that using the products together was recommended were obstacles to consistent condom use with the diaphragm/gel. Concerns about protection from HIV and pregnancy, recognition that the diaphragm was not yet proven to prevent HIV or sexually transmitted infections, and the trial context were facilitators. Understanding selective study product use in HIV prevention trials may inform improved adherence counseling and male involvement strategies.
AIDS education and prevention: official publication of the International Society for AIDS Education 02/2012; 24(1):54-67. · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We examined the effect of becoming HIV-positive on contraceptive practices in a Phase III randomised controlled trial of the diaphragm for HIV prevention. We coded self-reported contraceptive use into seven categories of methods in order of effectiveness. We compared the proportion using each category of contraception at baseline and last visit between women who did and did not become HIV-positive. We compared changes in the proportion using each category of contraception from baseline to last visit and calculated the percentage of women that moved to a more or less effective method category or stayed the same. We examined immediate and long-term changes in contraceptive use category after learning HIV-positive status.
A total of 4645 women remained HIV-negative and 309 became HIV-positive. The proportion using each category of contraception was similar between groups at baseline and last visit. In both groups approximately one-fifth changed to a less effective method category between baseline and last visit. Few women reported using long-acting methods. Among HIV-positive women, shorter-term changes in the proportion using each category of contraception were similar to longer-term changes, though somewhat more women were using a method in the same category 3 months after seroconversion.
Learning about HIV-positive status did not appear to significantly change patterns of use of effective contraceptives or the probability of switching to a more or less effective method. Information about, and access to, long-acting methods should receive more attention and be a routine part of family planning programmes and prevention trials.
Journal of Family Planning and Reproductive Health Care 07/2011; 37(4):204-8. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
AIDS and Behavior 07/2011; 15(5):959-69. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We explored factors associated with differential HIV incidence among women participating in a HIV prevention trial in Harare, Durban, and Johannesburg. The trial had shown no effect of the intervention (diaphragm and lubricant gel) on HIV incidence.
A prospective cohort analysis was conducted of trial participants followed for 12-24 months. Sociodemographic, biological, and behavioral data were collected at baseline and at quarterly visits. Factors associated with HIV incidence were estimated using multivariable Cox regression models, stratified by study location. Attributable risk was calculated from the adjusted hazard ratios (AHR).
There were 309 incident HIV infections among the 4948 women in the analysis. HIV incidence was highest in Durban [6.75/100 person-years; 95% confidence interval (CI): 5.74 to 7.93], lower in Johannesburg (3.33/100 person-years; 95% CI: 2.51 to 4.44), and lowest in Harare (2.72/100 person-years; 95% CI: 2.26 to 3.26). Sexually transmitted infections were important risk factors in Harare [prevalent herpes simplex virus type 2 (HSV2) AHR = 2.56, 95% CI: 1.61 to 4.06; incident HSV2 AHR = 12.60, 95% CI: 2.13 to 21.87; Neisseria gonorrhoeae AHR = 6.82, 95% CI: 2.13 to 21.87] and in Durban (prevalent HSV2 AHR = 1.64, 95% CI: 1.07 to 2.51; N. gonorrhoeae AHR = 4.40, 95% CI: 2.07 to 9.39). In Durban, having multiple partners (adjusted odds ratio (AOR) = 1.78 95% CI: 1.11 to 2.85) and sex although a partner was under the influence of alcohol/drugs (AOR = 1.51 95% CI: 1.05 to 2.16) significantly increased risk, whereas in Johannesburg, sexual debut <16 years (AOR = 2.60 95% CI: 1.30 to 5.17) was a strong predictor of HIV acquisition.
Important differences were seen in drivers of HIV incidence at the 3 study locations. Results from this analysis imply that targeted HIV programing could have a large impact on incident HIV infection in women, and that the most effective approach will likely vary based on knowledge of the local situation/epidemiology.
[Show abstract][Hide abstract] ABSTRACT: There is little data on contraceptive effectiveness or use patterns from sub-Saharan Africa.
We analyzed data from women at risk of pregnancy (n=4905) in the Methods for Improving Reproductive Health in Africa trial of the diaphragm for HIV prevention. We described reported contraceptive method use and calculated rates of pregnancy by contraceptive method. We compared time to first pregnancy by study arm (condoms or condoms plus diaphragm), and estimated a Cox proportional hazards model to identify predictors of pregnancy.
Condoms (25.8%), injectables (25.4%) and OC (21.6%) were the most commonly used methods; long-acting method use was rare. During the trial, 51.6% of women used the same method, 27.4% switched to a more effective method and 20.9% switched to a less effective method; 21.4% of women became pregnant. Pregnancy rates by contraceptive group mirrored published estimates; frequency of study product use was not associated with pregnancy.
Long-acting methods of contraception should be made available in HIV prevention trials and to women in Southern Africa.
[Show abstract][Hide abstract] ABSTRACT: Methods for Improving Reproductive Health in Africa (MIRA), a phase III HIV prevention trial, was conducted among 5039 Zimbabwean and South African women to test the Ortho All-Flex diaphragm and Replens(®) lubricant gel. Among the 2418 intervention group participants, 105 women who had completed the trial and 41 male partners participated in focus group discussions and in-depth interviews about the acceptability of the diaphragm and gel and their experiences using the study products. Women who participated in the qualitative study had exited the trial in the prior nine months, were HIV negative, and used the diaphragm and gel for 12-24 months. The comprehensive and flexible conceptual framework was applied to investigate the salient attributes for acceptability of the products as potential HIV prevention methods, and emerging themes for acceptability were framed within three categories of attributes (product, relationship, and sexual intercourse attributes). Both diaphragm and gel were found to be highly acceptable in the study group, and the gel was popular due to its effect of enhancing sexual pleasure. Some of the important product attributes influencing acceptability as reported by users were convenience, ease of use, dual use potential for contraception and disease prevention, and being female-initiated. It was also noted that some elements (such as sexual pleasure, couple communication, and the necessity of diaphragm negotiation) could be more important than others in terms of influencing product acceptability and use. Acceptability attributes reflective of the broader contextual environment (beliefs generated in the trial community suggesting preventive efficacy - preventive method optimism - and gendered norms favoring male superiority in sexual decision making) also emerged as important themes. The high level of acceptability of the diaphragm and gel among MIRA trial participants and their male partners is an indicator of the continued need for an effective female-initiated product.
AIDS Care 04/2011; 23(8):1026-34. · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assess the relative contribution of viral and bacterial sexually transmitted infections (STIs) on HIV acquisition among southern African women in a nested case-control study within the Methods for Improving Reproductive Health in Africa (MIRA) trial. Cases were women with incident HIV infection; controls were HIV-uninfected at the time of case seroconversion selected in a 1 to 3 case to control ratio (risk-set sampling), matched on study site and time of follow-up. Conditional logistic regression models were used to calculate adjusted odds ratios (AORs) and population-attributable fractions (PAF). Among 4948 enrolled women, we analysed 309 cases and 927 controls. The overall HIV incidence rate was 4.0 per 100 women-years. The incidence of HIV infection was markedly higher in women who had prevalent Herpes simplex virus type 2 (HSV-2) (AOR: 2.14; 95% confidence interval [CI]: 1.55-2.96), incident HSV-2 (AOR: 4.43; 95% CI: 1.77-11.05) and incident Neisseria gonorrhoeae (AOR: 6.92; 95% CI: 3.01-15.90). The adjusted PAF of HIV incidence for prevalent HSV-2 was 29.0% (95% CI: 16.8-39.3), for incident HSV-2 2.1% (95% CI: 0.6-3.6) and for incident N. gonorrhoeae 4.1% (95% CI: 2.5-5.8). Women's greatest risk factors for HIV acquisition were incident bacterial and viral STIs. Women-centred interventions aimed at decreasing HIV incidence in young African women need to address these common co-morbid conditions.
International Journal of STD & AIDS 04/2011; 22(4):218-24. · 1.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the context of a multisite HIV prevention trial in Southern African women, we examined the effectiveness of the Ortho All-Flex Diaphragm, lubricant gel (Replens) and condoms compared to condoms alone on the incidence of herpes simplex virus type 2 (HSV-2) infections.
We analysed data from 2016 sexually active women in Zimbabwe and South Africa. Women were followed quarterly, and specimens obtained at the closing visit from previously HSV-2 seronegative women were retested for HSV-2 antibodies using Focus HerpeSelect Elisa. The first visit at which the participant tested positive for HSV-2 was defined by back-testing. We compared the incidence of HSV-2 after randomisation between study arms in both intent-to-treat (ITT) and per-protocol populations.
210 women acquired HSV-2 during study participation (HSV incidence: 6.8 cases/100 women years). Allocation to the intervention arm was found to offer no benefit in reduction of HSV-2 by modified ITT (HR 1.03, 95% CI 0.78 to 1.35; p=0.85) or per protocol analysis (HR 0.87, 95% CI 0.61 to 1.24; p=0.45).
HSV-2 infection was common in the study population as detected by type-specific Elisa testing. Provision of diaphragm and lubricant gel offered no additional protection against HSV-2 acquisition over male condoms alone.