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The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward. [ABSTRACT FROM AUTHOR]

Background: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes. Standard-of-care (SOC) for BV are antibiotics; however, cure rates are low. Probiotics for vaginal health may be useful in improving cure and recurrence although the regulatory framework governing probiotics and the conduct of randomized clinical trials to evaluate these has not been established in South Africa. We performed an exploratory single-blind trial evaluating a commercial oral-vaginal-combination probiotic as adjunct to SOC for BV treatment.Methods: Women with symptomatic vaginal discharge were screened for BV and common sexually transmitted infections (STIs). BV+ (Nugent 7-10) but STI- women were randomized to vaginal metronidazole alone (n = 12) or to metronidazole followed by a commercial oral/vaginal probiotic (n = 18). The primary qualitative outcome was to test the regulatory landscape for conducting randomized probiotic trials in South Africa; and acceptability of vaginal application by women. BV cure at 1 month (Nugent≤3) was the primary quantitative endpoint. Secondary quantitative endpoints were BV recurrence, symptoms, vaginal microbiota and genital cytokine changes over 5 months post-treatment.Results: The  South African Health Products Regulatory Authority (SAHPRA) reviewed and approved this trial. As probiotics continue to be regulated as health supplements in South Africa, SAHPRA required a notification application for this trial. Acceptability and adherence to the oral and vaginal application of the probiotic were high, although women reported a preference for oral capsules. 44.8% of women cleared BV one-month post-treatment, and no significant differences in BV cure (RR = 0.52, 95% CI = 0.24-1.16), recurrence, vaginal pH, symptoms, microbiota or vaginal IL-1α concentrations were found between SOC and intervention groups in this pilot study with an over-the-counter product.Conclusion: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial laid the foundation for planned larger trials of improved probiotic products for vaginal health in South Africa. Although adherence to the vaginally delivered probiotic was high, women preferred oral application and we recommend that improvements in the content and method of application for future probiotics for vaginal health should be considered.Trial Registration: This trial was registered on 17 October 2017 with the South African National Clinical Trial Register ( http://www.sanctr.gov.za/ ; BV-trial1; DOH-27-1117-5579 ). [ABSTRACT FROM AUTHOR]

Introduction: Incorporating end-user input into the design of new vaginal microbicides for women is key to optimizing their uptake, consistent use, and, ultimately, success in combatting the heterosexual HIV epidemic. Methods: The Quatro Study assessed four placebo forms of vaginally inserted HIV-microbicides among young microbicide-naïve African women: on-demand film, insert and gel, and monthly ring. Participants randomly used each product for 1 month and provided product satisfaction ratings (1–5 scale), and opinions on product attributes and potential alternative designs. Qualitative data were collected through focus group discussions at study exit. Multivariable associations between attribute opinions and overall product rating were examined using Poisson regression models with robust standard errors to assess the attributes most influential to satisfaction. Results: Overall opinions of products and their individual attributes were generally positive; all products were rated either 4 or a 5 by ≥ 50% of participants. Attributes related to ease of use and interference with normal activities were the most salient predictors of satisfaction. Preferences for duration of use tended toward relatively shorter use periods for the ring (i.e., 1–3 months vs. 12 months) and for coitally independent dosing for the on-demand products. Conclusions: How well a product fit in with participants' lifestyles was important to their overall satisfaction. For on-demand products, greater flexibility around timing of use was desired, to avoid coital dependency of the dosing. [ABSTRACT FROM AUTHOR]

The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of ‘place’ and ‘timing’ in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products. [ABSTRACT FROM AUTHOR]

Preferences and practices related to the vaginal condition have implications for the use of vaginal HIV prevention products. The authors used qualitative methods to explore narratives relating to the vaginal state amongst women in South Africa, Uganda, and Zimbabwe who had previously participated in a biomedical HIV prevention trial. They investigated women's behaviors related to optimizing the vaginal state, experiences and perceptions of the gel's effect on the vaginal state and on penile-vaginal intercourse, women's narratives on male partner perceptions, and how preferences relating to the vaginal state may have interfered with gel use. [ABSTRACT FROM AUTHOR]

Accurate and objective measurement of adherence is critical in microbicide trials. We compared two applicator tests: visual inspection of returned empty tenofovir gel applicators (VIREA) and ultraviolet light (UVL) assessment in terms of sensitivity and specificity, and for concordance. Sensitivity and specificity analysis of 24 control applicators (12 known-inserted and 12 sham-inserted) at 4-months after receipt was 75.0 and 66.7 % for VIREA and 83.3 and 91.7 % for UVL, respectively. After an additional 3 months of storage sensitivity and specificity was 100 and 58.3 % for VIREA and 100 and 66.7 % for UVL, respectively. In January 2015, 1316 empty applicators were returned as used by 115 participants enrolled at one site in a randomized controlled trial. Assessment outcomes showed 78.8 % agreement between the techniques. Methods concurred that 22.0 % of the returned empty applicators appeared unused. By UVL assessment, 40.0 % of returned empty applicators had no evidence of vaginal insertion, translating to a potential 28.0 % less product used as compared to that returned as used by women. UVL assessment may be considered a more accurate and less subjective measure of adherence as compared to VIREA. [ABSTRACT FROM AUTHOR]

Consistent over-reporting of product use limits researchers' ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting. [ABSTRACT FROM AUTHOR]

Product sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679 [ABSTRACT FROM AUTHOR]

To assess the views of potential end-users of a microbicide in KwaZulu-Natal regarding the characteristics that would justify further development, three focus group discussions were conducted in 2009 with 23 local staff members working on a microbicide clinical trial, 20 former trial participants and 14 Community Advisory Board members not enrolled in the trial, in an area with high HIV incidence and low consistent condom use. All participants agreed on the need for additional HIV prevention options that are as effective as possible and can be used by women. The majority of respondents stated that even a highly acceptable HIV prevention option with protection as low as 30% would still be an important addition to condoms for women; that a partially protective microbicide would have to be introduced as part of the existing prevention messages in order to continue promoting condom use; that there should eventually be a choice between antiretroviral (ARV) and non-ARV-based microbicides and a choice of how and where to access microbicides. Respondents also felt it would be important to make plans for access to a microbicide that can offer protection, even if partial, rather than wait to find out if alternative microbicides are equally or more effective. Potential end-users in a high HIV prevalence area believe that a partially effective microbicide would be an important addition to the limited HIV prevention options for women. The significant challenges of introducing a partially protective HIV prevention option were recognised, but seen as ones worth facing, as well as an opportunity to lay the ground work for the introduction of more efficacious HIV prevention methods in the future. [ABSTRACT FROM AUTHOR]

Vaginal microbicide gel trials for HIV prevention may require withdrawal of study product when a woman becomes pregnant. We assessed the potential impact of withdrawals in four trials by comparing self-reported sexual behavior pre- and post-pregnancy detection: (1) behavior in the month prior to positive pregnancy test versus behavior reported at the subsequent monthly visit; (2) behavior changes according to pregnancy status at the subsequent visit (continuing pregnancy versus not); (3) average sexual behaviors reported for all months prior to pregnancy detection versus all months after pregnancy was no longer detected; and (4) behavior changes among participants never testing positive for pregnancy. Pregnancy detection was associated with immediate reductions in self-reported numbers of partners and sex acts. The proportion of acts in which study gel was used following a negative pregnancy test did not return to pre-pregnancy levels. Pregnancies complicate the conduct and interpretation of vaginal microbicide trials when product must be withdrawn. [ABSTRACT FROM AUTHOR]

The first vaginal microbicide was recently proven effective in clinical trials. We assessed the willingness of clinicians to integrate microbicides into HIV prevention practices in Southern Africa, where women face elevated HIV risks. We conducted in-depth interviews ( n = 60) and nationally representative surveys ( n = 1,444) in South Africa and Zimbabwe with nurses and physicians. Over half of clinicians (58%) were aware of microbicides, with physicians far more likely than nurses to be familiar. Clinicians, including those in rural areas, were generally willing to discuss microbicides, a female-initiated method less effective than the condom, particularly when condom use was unlikely (70%). Fewer would include microbicides while counseling adolescents (51%). Most clinicians (85%) thought their patients would use microbicides; greater clinician familiarity with microbicides was significant for support. Training for both nurses and physicians prior to introduction is critical, so they have sufficient knowledge and skills to offer a microbicide upon availability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Women worldwide use various vaginal practices to clean or modify their vulva and vagina. Additional population-level information is needed on prevalence and motivations for these practices, characteristics of users, and their adverse effects. Methods: This was a household survey using multistage cluster sampling in Tete, Mozambique; KwaZulu-Natal, South Africa; Yogyakarta, Indonesia; and Chonburi, Thailand. In 2006-2007, vaginal practices and their motivations were examined using structured interviews with women 18-60 years of age ( n=3610). Results: Prevalence, frequency, and motivations varied markedly. Two thirds of women in Yogyakarta and Chonburi reported one or more practices. In Yogyakarta, nearly half ingest substances with vaginal effects, and in Chonburi, external washing and application predominate. In Tete, half reported three or four current practices, and a quarter reported five or more practices. Labial elongation was near universal, and 92% of those surveyed cleanse internally. Two third's in KwaZulu-Natal practiced internal cleansing. Insertion of traditional solid products was rare in Chonburi and Yogyakarta, but one tenth of women in KwaZulu-Natal and nearly two thirds of women in Tete do so. Multivariate analysis of the most common practice in each site showed these were more common among less educated women in Africa and young urban women in Asia. Explicit sexual motivations were frequent in KwaZulu-Natal and Tete, intended for pleasure and maintaining partner commitment. Practices in Chonburi and Yogyakarta were largely motivated by femininity and health. Genital irritation was common at African sites. Conclusions: Vaginal practices are not as rare, exotic, or benign as sometimes assumed. Limited evidence of their biomedical consequences remains a concern; further investigation of their safety and sexual health implications is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Background: Carraguard''s safety and acceptability was assessed among women in Gugulethu and Ga-Rankuwa, South Africa. Study Design: A randomized, placebo-controlled, triple-blind trial was conducted in HIV-negative, nonpregnant women who inserted Carraguard or placebo at least three times a week, including before vaginal sex, for 6 to 12 months. Monthly visits included pelvic examination, sexually transmitted infection (STI) testing/treatment and HIV counseling/testing. Acceptability was assessed quarterly. Results: Of 400 women (205 Carraguard, 195 placebo) enrolled, 328 (77%) completed at least 6 months. Incidence of genital epithelial disruption was similar between the Carraguard (13.6 per 100 woman-years) and placebo (21.3 per 100 woman-years) groups (relative risk, 0.64; 95% confidence interval, 0.37–1.10); there were no significant differences in rates of HIV/STI, though the study was not powered to determine effectiveness. Only 2% of adverse events were judged possibly related to (either) gel. More than 94% of women reported at least once liking the gel very much. Conclusions: Carraguard was not associated with more vaginal, cervical or external genital irritation than placebo, and it was acceptable when used approximately 3.5 times per week, including during sex. [Copyright &y& Elsevier]

The article focuses on joint U.S. and South African research findings indicating that the vaginal use of a tenofovir gel by women before and after sex protects against sexually transmitted HIV.

Two sister studies have been launched in Africa to evaluate the ability of a new monthly vaginal ring containing the antiretroviral drug dapivirine to safely prevent new HIV infections in women.• The Ring Study, under the aegis of the International Partnership for Microbicides, plans to enroll 1,650 women at four sites in South Africa. Researchers look to start enrollment at additional sites in Rwanda and Malawi pending regulatory and ethics approvals. • The second study, ASPIRE (A Study to Prevent Infection with a Ring for Extended Use), is being led by the Microbicide Trials Network. Investigators plan to enroll some 3,476 women at 17 sites in Malawi, Uganda, South Africa, Zambia, and Zimbabwe. [ABSTRACT FROM AUTHOR]

Question: In HIV-negative South African women, does pericoital application of tenofovir gel reduce risk for herpes simplex virus type 2 (HSV-2)? Methods Design: Substudy of a randomized placebo-controlled trial* (Centre for the AIDS Programme of Research in South Africa [CAPRISA] 004 trial). ClinicalTrials.gov NCT00441298. Allocation: Concealed.† Blinding: Blinded† {patients, clinicians, data collectors, outcome adjudicators, statisticians, and safety committee}‡. Follow-up period: Mean 18 months. Setting: {1 urban clinic and 1 rural clinic in KwaZulu-Natal,}* South Africa. Patients: 429 HIV-negative South African women {18 to 40 years of age}* (mean age 22 y) who were negative for HSV-2 antibodies, {were sexually active, and used a nonbarrier form of contraception}*. Exclusion criteria included {creatinine clearance < 50 mL/min, genital deep epithelial disruption, untreated sexually transmitted infection or reproductive tract infection, pregnancy, or plans to become pregnant or relocate}*. Intervention: Tenofovir gel (n = 205) or placebo gel (n = 224) in prefilled vaginal applicators. 1 dose of gel was inserted within 12 hours before sexual intercourse and a second dose as soon as possible within 12 hours after intercourse. The maximum number of doses was 2 in 24 hours. Outcomes: HSV-2 infection (seroconversion assessed by enzyme-linked immunosorbent assay [ELISA] or Western Blot). Patient follow-up: 98% (intention-to-treat analysis). Main results: Tenofovir reduced risk for HSV-2 infection compared with placebo (Table). Confirmation of negative HSV-2 status at baseline, positive HSV-2 status at final study visit, and samples with equivocal results on ELISA confirmed that tenofovir gel reduced HSV-2 incidence (5.5 vs 12.3 cases/100 person-y, P = 0.005). Conclusion: In HIV-negative South African women, pericoital application of tenofovir gel reduced risk for herpes simplex virus type 2 infection. [ABSTRACT FROM AUTHOR]