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The objective of this study was to describe the impact of intense counseling to reduce vaginal hygiene practices and its effect on bacterial vaginosis. A secondary data analysis of the HIV Prevention Trials Network 035 study was undertaken, focusing on HIV-negative, nonpregnant women who were at least 18 years old, in seven African sites and one US site. At enrollment and during follow-up quarterly visits, vaginal hygiene practices were determined by face-to-face administration of a behavioral assessment questionnaire. Vaginal hygiene practices were categorized as insertion into the vagina of (1) nothing, (2) water only, and (3) other substances with or without water. Each practice was quantified by frequency and type/combination of inserted substances. At quarterly visits, diagnosis of bacterial vaginosis was made using the Nugent score. Trends for vaginal hygiene practices and bacterial vaginosis were evaluated using generalized estimating equation models. A total of 3087 participants from the HIV Prevention Trials Network 035 study were eligible for this analysis. At enrollment, 1859 (60%) reported recent vaginal hygiene practices. By one year, this figure had decreased to 1019 (33%) with counseling. However, bacterial vaginosis prevalence remained consistent across the study observation period, with 36%-38% of women testing positive for the condition ( p for trend = 0.27). Overall, those who reported douching with water only (AOR = 1.03, 95%CI: 0.94-1.13) and those who reported inserting other substances (AOR= 0.98, 95%CI: 0.88-1.09) in the past quarter were not more likely to have bacterial vaginosis compared to those who reported no insertions. However, in South Africa, an increase in bacterial vaginosis was seen among those who reported inserting other substances (AOR: 1.48, 95%CI: 1.17, 1.88). In conclusion, targeted counseling against vaginal hygiene practices resulted in change in self-reported behavior but did not have an impact on bacterial vaginosis diagnosis in all but one site.

We studied the acceptability of tenofovir gel among HIV-infected and uninfected men who were exposed to it during vaginal intercourse. The gel was found to be highly acceptable to most men, the large majority indicating they would probably use it in the future if they were concerned about HIV and the product were available. Men liked the gel's transparency and odorless qualities, although reactions to its viscosity were more varied. Men acknowledged women's rights to self-determination concerning HIV-prevention, yet considered that women's covert use of the product was more acceptable in the context of 'one-night-stands' than in stable relationships, for which dialogue on protection measures was preferred. Restrictions to couples' habitual sexual repertoire and the protocol requirement to use condoms resulted in complaints. Microbicide trials that do not require condom use from men who don't typically use them may provide a more accurate assessment of acceptability. Consistent microbicide use may be contingent on its ease of incorporation into typical sexual practices, type of sexual partnership and contextual issues. [ABSTRACT FROM AUTHOR]

Use of HIV prevention methods may vary for women by types of sexual partners. In a microbicide safety and effectiveness trial (HPTN 035) differences in adherence to a microbicide study gel were compared between women with new versus ongoing partnerships over time. 1,757 women in the three HPTN 035 trial's arms completed the Follow-up Partner Status (FPS) questionnaire at their last study visit. Women married at baseline were asked if they had the same husband, new husband or new partner. Unmarried women were asked if they had changed partners or married. Self-reported gel adherence during the last sex act was compared at each quarterly visit between women with ongoing versus new partners. High gel adherence was compared with low gel adherence (85-100 vs. <85 % of last vaginal sex acts reported with gel use, respectively) in multivariable models to assess associations with partner change. Overall 7 % of women (n = 123) reported a new partner and 41 % (51) of those reported a new husband. Median gel adherence was reported to be 100 % in women with ongoing partners and 75 % for women with new partners (p < 0.001). In women reporting no gel use in their last sex act, only 12.5 % of the women with a new partner and none of those with an ongoing partner reported using condoms (p < 0.001). Fewer women with new partners reported using both the gel and condom during the last sex act as compared to women with ongoing partners (median 50 vs. 71.4 %, p < 0.001). After adjusting for age, site, education level, and sexual frequency, women with ongoing partners were more likely to report high gel adherence than those with new partners (AOR 2.5, 95 % CI 1.6, 3.9). This pattern persisted when gel use over time was compared between women with new versus ongoing partners. In the HPTN 035 trial, women with new partners had higher HIV incidence and reported less gel use and higher condom use. Specific counseling and support are needed to help women use potential HIV prevention methods, including microbicides, when they are changing partners.

Objective: To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission., Design: Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm., Methods: Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up., Results: The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89)., Conclusion: The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated.

Background: The study was conducted to assess socio-behavioral and biological factors associated with unplanned pregnancy in the US cohort of a microbicide trial., Study Design: We conducted a mixed-method, nested case-control study of risk factors for pregnancy within the US cohort of the microbicide trial HPTN 035. We developed an instrument to assess attitudes and beliefs about fertility control/contraceptive utilization among 122 women. Cases were HPTN 035 participants who became pregnant while enrolled, matched by time on study 1:4 with controls. Univariable and multivariable analysis were performed with pregnancy as the outcome of interest., Results: Contraceptive method change during the trial was associated with unplanned pregnancy (OR=1.76). Participant desire/partners' desire for future children (OR=4.95) and young age (OR=0.88 annually above age 19 years) were independently associated with unintended pregnancy., Conclusion: Within a trial that enroll heterosexually active women, there may be ways to identify those at highest risk of becoming pregnant a priori., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: In this phase I safety trial of tenofovir gel, a candidate vaginal microbicide for human immunodeficiency virus (HIV) prevention, a mixed-methods design was used to gather acceptability data among women participants. The impact of acceptability factors on use of the gel and the relationship between qualitative and quantitative acceptability data are explored., Methods: Participants included low-risk, HIV-uninfected, and clinically stable HIV-infected women. Participants were enrolled into cohorts stratified by HIV serostatus, sexual activity, gel concentration, and frequency of use. Quantitative data were collected via interviewer-administered structured questionnaires. Qualitative data were collected via semistructured small group discussions., Results: Although 94% of participants stated they would "probably" or "definitely" use tenofovir gel, a range of responses emerged on multiple domains relevant to microbicide acceptability during the qualitative discussions. Lubrication, leakage, sexual pleasure, and the possibility of covert use were central to women's qualitative assessments of tenofovir gel., Conclusions: Quantitative results indicate that tenofovir vaginal gel was acceptable to almost all users, while qualitative findings indicate that acceptability is complex, varies among users, and is likely shaped by a variety of contextual factors that manufacturers will need to consider to optimize use-effectiveness. Because of the differences in the qualitative and quantitative responses, the authors argue that future trials of candidate microbicides should include strategic collection of mixed-methods microbicide acceptability data.

Objectives: Few studies of topical microbicides have assessed their safety in HIV-infected women. We conducted this study to evaluate the safety and acceptability of 6% cellulose sulfate (CS) gel as a vaginal microbicide in sexually abstinent and active HIV-infected women., Methods: Fifty-nine HIV-infected women were enrolled in a randomized double-blind placebo-controlled study comparing 6% CS to placebo gel used for 14 days. Sexually abstinent women applied gel once or twice daily and sexually active women used gel once daily., Results: CS gel was safe with no reported severe or life-threatening adverse events (AE). Thirty-nine (66%) of the participants experienced urogenital AE judged as probably or possibly related to gel. The majority (51%) of these participants reported only mild events. Fewer women (62%) who used CS experienced urogenital AE than those assigned to placebo gel (70%) (P = 0.59). Eleven (19%) women experienced intermenstrual bleeding judged to be probably or possibly related to gel use (four in the CS and seven in the placebo gel group). There was no increase in AE by frequency of gel use or sexual activity with the exception of abdominal/pelvic pain which was noted more frequently with twice daily use among sexually abstinent women. Women and men found the gel highly acceptable., Conclusions: This Phase I study demonstrated that CS vaginal gel was safe, well tolerated and acceptable by HIV-infected women and their male partners. Thus, further development of CS is warranted as a potential method to prevent HIV transmission and acquisition.

Purpose: Vaginal microbicides will provide a woman-initiated prevention strategy that could substantially reduce rates of HIV infection. The acceptability of microbicides will greatly influence the use and, hence, effectiveness of such products. In this study, the acceptability of an investigational microbicide, PRO 2000 Gel (Indevus Pharmaceuticals, Inc., Lexington, MA), was assessed, and women's opinions about microbicides and their potential for real world use were gathered., Methods: Quantitative and qualitative data were collected from 30 U.S. and 33 South African women. All sexually active HIV-uninfected women and all sexually abstinent HIV-infected women participating in this phase I clinical trial stated in a survey that they would use PRO 2000 Gel if they had reason to be concerned about HIV and the product were available. Qualitative data, however, provided insight into the nuances of acceptability ratings. Women rated product safety, ease of use, and positive effects on sexual pleasure among the most important characteristics of acceptable microbicides., Results: Opinions regarding product leakage, contraceptive capability, and the ability to be used without partners noticing, as well as characteristics of the product itself, varied substantially based on the context of sex and perceptions of risk within each individual woman's life., Conclusions: As microbicide development continues and the first investigational products move into efficacy trials, the needs and preferences of those women who constitute the potential users of microbicides become paramount. Providing woman-initiated microbicides that are safe, easy to use, and pleasurable will be key to the impact these products will have on the AIDS epidemic worldwide.

Objectives: To evaluate once or twice daily vaginal exposure to 2 and 4% PRO 2000 Gel, a naphthalene sulfonate polymer microbicide, in sexually active HIV-uninfected women to determine the highest tolerated frequency and concentration combination, and to assess this in sexually abstinent HIV-infected women., Methods: Sixty three women from Providence, Philadelphia, Durban and Johannesburg were enrolled after being screened to exclude pre-existing illnesses and were instructed to use the product once or twice daily for 14 intermenstrual days. They underwent colposcopy prior to product use and after 14 days of product use, with a pelvic examination at day 7., Results: The product was well tolerated, with no serious adverse events, even though 73% of the participants had at least one adverse experience: 82% of these were classified as mild, and over 90% of the findings and symptoms were localized to the genital tract. Women who used the 4% gel twice daily tended to have more adverse events than all the other groups. Three participants did not complete the study; one because of Herpes simplex virus cervicitis, the second because of epithelial disruption, and the third because she became pregnant. The remaining participants adhered to the study protocol and indicated that they would use the product if it were shown to be effective., Conclusions: PRO 2000 Gel was safe and well tolerated in sexually active HIV-uninfected and sexually abstinent HIV-infected women, enabling the product to be considered for evaluation in efficacy trials.

Background: New multi-purpose prevention technology (MPT) products are needed to prevent human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2). In this study, we evaluated a fast-dissolve insert that may be used vaginally or rectally for prevention of infection. Objective: To describe the safety, acceptability, multi-compartment pharmacokinetics (PK), and in vitro modeled pharmacodynamics (PD) after a single vaginal dose of an insert containing tenofovir alafenamide (TAF) and elvitegravir (EVG) in healthy women. Methods: This was a Phase I, open-label, study. Women (n=16) applied one TAF (20mg)/EVG (16mg) vaginal insert and were randomized (1:1) to sample collection time groups for up to 7 days post dosing. Safety was assessed by treatment-emergent adverse events (TEAEs). EVG, TAF and tenofovir (TFV) concentrations were measured in plasma, vaginal fluid and tissue, and TFVdiphosphate (TFV-DP) concentration in vaginal tissue. PD was modeled in vitro by quantifying the change in inhibitory activity of vaginal fluid and vaginal tissue against HIV and HSV2 from baseline to after treatment. Acceptability data was collected by a quantitative survey at baseline and post treatment. Results: The TAF/EVG insert was safe, with all TEAEs graded as mild, and acceptable to participants. Systemic plasma exposure was low, consistent with topical delivery, while high mucosal levels were detected, with median TFV vaginal fluid concentrations exceeding 200,000 ng/mL and 1,000 ng/mL for up to 24 hours and 7 days post dosing, respectively. All participants had vaginal tissue EVG concentrations of > 1 ng/mg at 4 and 24 hours post dosing. The majority had tissue TFV-DP concentrations exceeding 1000 fmol/mg by 24 - 72 hours post dosing. Vaginal fluid inhibition of HIV-1 and HSV-2 in vitro significantly increased from baseline and was similarly high at 4 and 24 hours post dosing. Consistent with high tissue TFV-DP concentrations, p24 HIV antigen production from ectocervical tissues infected ex vivo with HIV-1 significantly decreased from baseline at 4 hours post dosing. HSV-2 production from tissue also decreased post treatment. Conclusions: A single dose of TAF/EVG inserts met PK benchmarks, with PK data supporting an extended window of high mucosal protection. PD modeling supports mucosal protection against both HIV-1 and HSV-2. The inserts were safe and highly acceptable. [ABSTRACT FROM AUTHOR]

The World Health Organization recommends pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV infection. The aim of this analysis is to quantify the individual risk of HIV infection over time, using a large database of high-risk individuals (n = 5583). We used data from placebo recipients in five phase III PrEP trials: iPrEx, conducted in men who have sex with men and transgender women; VOICE, conducted in young women at high sexual risk; Partners PrEP, conducted in HIV serodiscordant heterosexual couples; TDF2, conducted in high-risk heterosexual men and women; and BTS, conducted in persons who inject drugs. The probability of HIV infection over time was estimated using NONMEM7.4. We identified predictors of HIV risk and found a substantial difference in the risk of infection among and within trial populations, with each study including a mix of low, moderate, and high-risk individuals (p < 0.05). Persons who were female at birth were at a higher risk of HIV infection than people who were male at birth. Final models were integrated in a tool that can assess person-specific risk and simulate cumulative HIV risk over time. These models can be used to optimize future PrEP clinical trials by identifying potential participants at highest risk. [ABSTRACT FROM AUTHOR]

We triangulated quantitative and qualitative assessments to evaluate participants' acceptability of 0.05% dapivirine rectal microbicide (RM) gel administered via two separate modalities (a rectal applicator and an artificial phallus for use as a coital simulation device) as part of a Phase I trial (N = 14) among men who have sex with men (MSM) randomized using a 1:1 ratio. Overall, participants reported favorable acceptability of the gel (n = 11; 78.6%), the same or more at the end of the study compared to when they started the study. Additionally, when discussing their preferred administration modality, they noted that both methods had positive qualities but also potential areas of improvement. Our findings underscore the need to create multiple delivery methods for a future microbicide gel (i.e., with and without the need for an applicator) and highlight the importance of offering MSM choices in how biomedical HIV prevention strategies are delivered. [ABSTRACT FROM AUTHOR]

South Africa has the highest number of HIV infected individuals in the world. The primary objective of the current study was to describe temporal changes in HIV incidence rates using the data from 9,948 women who enrolled in one of the six HIV prevention trials conducted in KwaZulu-Natal, South Africa. Characteristics of the study population were presented and compared across the four study periods: 2002–2004, 2005–2008, 2009–2011 and 2012–2016. HIV infection rates increased from 6.2 to 9.3 per 100 person-year over the 15 years. These rates were as high as 14 per 100 person-year among women younger than 20 years age. Being single/not cohabiting, using injectable contraceptives, having less than two children, and diagnosed with STI(s) were associated with increased risk of HIV infection. These four factors were associated with 71%, 75%, 80% and 88% of the HIV seroconversions in four study periods. As the research continues to find ways of controlling the spread of the infections, quantifying the temporal trends in risk factors and their population-level impacts on HIV infection may have significant implications. This information may assist in developing effective counselling and education programs by targeting the sexually active single women and delivering more realistic messages. [ABSTRACT FROM AUTHOR]

Background: The pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women's views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population. Methods: We conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women's perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach. Results: A majority of women accepted participation in all trials. Women's views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation—principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions. Conclusions: The majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion. [ABSTRACT FROM AUTHOR]

Multiple prevention therapy has gained importance for the prevention and treatment of sexually transmitted diseases, especially HIV/AIDS. Antiretroviral drugs encapsulated in nanoparticles have been developed for efficient delivery of the drugs to the vaginal surface. Lactoferrin nanoparticles (LFNPs) encapsulating anticancer or antiretroviral drugs are found to be promising agents to specifically deliver drugs at the target sites. Recent studies indicate that the bioavailability is higher for antiretroviral drugs delivered by LFNPs than when the drugs are administered alone. Although LFNP-mediated drug delivery via the oral or vaginal route for the treatment of HIV/AIDS is promising, the effect of such administrations is not well studied. Drug-loaded LFNPs when administered to rats by the vaginal route did not show any effect on the reproductive performance, fertility, and postnatal development. Oral administration of drug-loaded LFNPs caused a significant decrease in litter size, whereas the reproductive performance and postnatal development remained normal. In our model system, the results indicate that vaginal administration of drug-loaded LFNPs appears safer and can be projected for the delivery of antiretroviral agents via the vaginal route. Abbreviations: LFNPs: lactoferrin nanoparticles; STIs: sexually transmitted diseases infections; NPs: nanoparticles; LF: lactoferrin; DL-LFNPs: drug loaded lactoferrin nanoparticles; MPT: multiple prevention techniques [ABSTRACT FROM AUTHOR]

In 2004, the first ever multi‐sited clinical trials studied the prospect of HIV biomedical prevention (referred to as pre‐exposure prophylaxis—'PrEP'). The trials were implemented at several international sites, but many officially closed down before they completed. At most sites, both scientists and community AIDS advocates raised concerns over the ethics and scientific rationales of the trial. Focusing on the Nigerian trial site, we detail the controversy that emerged among mostly Nigerian research scientists who scrutinized the research design and protocol. While some of the disputes, especially those pertaining to community engagement mechanisms, were ultimately resolved in international fora and implemented in later PrEP trials, concerns over science rationales and assumptions were never addressed. We argue that scientific rationales should be treated as ethical concerns and suggest that such concerns should be deliberated at host sites before the trial protocol is finalized. [ABSTRACT FROM AUTHOR]

Purpose: In the vagina of healthy reproductive-aged women, several microbial species maintain a finely tuned mutualistic relationship with the host providing the first-line of defense against the colonization by opportunistic pathogens, which are the leading cause of dysbiosis or vaginal infections (bacterial vaginosis, vulvovaginal candidiasis, and aerobic vaginitis). The use of probiotic lactobacilli to prevent vaginal infections has a good rationale, and an excellent safety record, but so far only a few strains have been clinically proven to be effective, particularly to prevent BV. The aim of the clinical trial was to evaluate the changes in Nugent score in women with intermediate vaginal microbiota treated with oral Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001 mixture, in combination with bovine lactoferrin RCX™ (Respecta®) or placebo, for 15 days.Methods: Vaginal swabs were collected from each woman at baseline and at the end of probiotic treatment and analyzed by RT-PCR. Both symptoms of abnormal vaginal micorbiota and adverse effects were assessed throughout the study.Results: The results showed that oral intake of lactobacilli/lactoferrin mixture led to significant vaginal colonization by L. acidophilus GLA-14 and L. rhamnosus HN001 showing that both strains can colonize vagina following oral ingestion. The effect of such colonization is correlated with the restoration of normal Nugent score (values 0-3) and an improvement of symptoms of abnormal vaginal micorbiota including itching and discharge.Conclusions: Oral consumption of lactobacilli/lactoferrin complex corroborates the effectiveness of using lactobacilli for supporting vaginal health and provides a rational basis for future studies on vaginal infections. [ABSTRACT FROM AUTHOR]

We examined young gay, bisexual, and other men who have sex with men’s (YGBMSM) usage patterns of a pre-coital, applicator-administered rectal placebo gel. An ethnically diverse sample of 94 YGBMSM (aged 18–30 years) were asked to insert hydroxyethylcellulose placebo gel rectally before receptive anal intercourse (RAI) and report their gel use through an interactive voice response system (IVRS) across 12 weeks. We used trajectory analyses to characterize participants’ use of the rectal gel over the 12 weeks, and examine whether these trajectories varied based on participants’ sociodemographic characteristics, sexual behaviors, application and insertion behaviors, and experiences using the placebo gel. A cubic model was the best fit for these longitudinal data, with two distinct trajectories of gel use observed. The first trajectory (‘High with Varying Gel Use per Week’) represented YGBMSM (N = 38; 40.3%) who reported using the rectal gel on several occasions per week. The second trajectory (‘Low and Consistent Gel Use per Week’) represented participants (N = 56; 59.7%) who reported a consistent average use of one gel per week. Participants in the High with Varying Gel Use Trajectory reported trying out a greater number of positions when inserting the gel across the 12-weeks than peers in the Low and Consistent Gel Use Trajectory. YGBMSM reporting more RAI occasions during the trial were more likely be present in the High with Varying Gel Use Trajectory than peers in the Low and Consistent Gel Use Trajectory. Future research examining how to facilitate gel application and adherence among YGBMSM is merited. [ABSTRACT FROM AUTHOR]

Background: Intravaginal practices (IVP) (cleansing or introducing products inside the vagina for hygiene, health or to please sexual partners) are common among women with HIV. IVP increase the risk of developing bacterial Vaginosis (BV), the most common genital infection associated with transmission of sexually transmitted infections and HIV. This study tested a pilot intervention to reduce IVP and BV in HIV infected women in Zambia.Methods: One hundred twenty-eight HIV infected women engaging in IVP were randomized to two conditions: enhanced standard of care (n = 70) and experimental (n = 58) from May 1, 2013 to February 28, 2014. All participants received a brief educational counseling session on discontinuation of IVP, and those with BV, were provided with medical treatment for BV. Women in the experimental condition received an additional group-based, culturally tailored intervention. Participants completed questionnaires assessing sexual risk factors and IVP and were assessed for BV using Nugent criteria at baseline, 6 months and 12 months.Results: At 12-month, the proportion of self-reported use of IVPs decreased in the experimental condition: soap (28% vs. 47%); cloth or a rag (19% vs. 38%); and traditional medicines (22% vs. 42%) (all p < 0.05)) compared with the enhanced standard of care condition. The prevalence of BV at 6 and 12 months did not differ by study condition but averaging over study condition, prevalence of BV decreased from 64.2% at baseline to 15.6% at 6 months (p < 0.01) and to 23.6% at 12 months (p = 0.15). Using an enhanced standard of care approach and an enhanced standard of care + a group intervention, IVP and BV decreased over time, but the experimental condition had greater reduction in self-reported use of IVP.Conclusions: Future studies should address interventions in communities with high burden of IVP, BV and HIV. Interventions that could be administered during routine medical care and decrease IVP and BV are needed, and should be considered part of women's health programs.Trial Registration Number: NCT03134924 (retrospectively registered 21st April 2017). [ABSTRACT FROM AUTHOR]

The success of women's microbicide use for HIV/AIDS prevention may hinge on health programs' ability to engage men to support it. In this qualitative study in Kenya, most women did not or would not tell their partners prior to initiating use, and/or would use despite their objections. Men generally did not agree with this, yet male partners of trial participants who discovered that their partners were using microbicides without their knowledge did not seem concerned. Findings suggest that efforts to engage men in microbicide use should avoid “awakening” patriarchal gender norms, and support women to use microbicides without involving their partners. [ABSTRACT FROM PUBLISHER]

The majority of phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDCs for further testing for efficacy in a phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDCs. Operating characteristics are demonstrated through simulation studies and are compared with existing methodology. Some brief discussion of implementation and available software is also provided. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individual-level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson-distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Protein microbicides containing neutralizing antibodies and antiviral lectins may help to reduce the rate of infection with human immunodeficiency virus ( HIV) if it is possible to manufacture the components in large quantities at a cost affordable in HIV-endemic regions such as sub-Saharan Africa. We expressed the antiviral lectin griffithsin ( GRFT), which shows potent neutralizing activity against HIV, in the endosperm of transgenic rice plants ( Oryza sativa), to determine whether rice can be used to produce inexpensive GRFT as a microbicide ingredient. The yield of OSGRFT in the best-performing plants was 223 μg/g dry seed weight. We also established a one-step purification protocol, achieving a recovery of 74% and a purity of 80%, which potentially could be developed into a larger-scale process to facilitate inexpensive downstream processing. OSGRFT bound to HIV glycans with similar efficiency to GRFT produced in Escherichia coli. Whole-cell assays using purified OSGRFT and infectivity assays using crude extracts of transgenic rice endosperm confirmed that both crude and pure OSGRFT showed potent activity against HIV and the crude extracts were not toxic towards human cell lines, suggesting they could be administered as a microbicide with only minimal processing. A freedom-to-operate analysis confirmed that GRFT produced in rice is suitable for commercial development, and an economic evaluation suggested that 1.8 kg/ha of pure GRFT could be produced from rice seeds. Our data therefore indicate that rice could be developed as an inexpensive production platform for GRFT as a microbicide component. [ABSTRACT FROM AUTHOR]

Background: The ethical concerns associated with HIV prevention and treatment research have been widely explored in South Africa over the past 3 decades. However, HIV cure research is relatively new to the region and significant ethical and social challenges are anticipated. There has been no published empirical enquiry in Africa into key informant perspectives on HIV cure research. Consequently, this study was conducted to gain preliminary data from South African HIV clinicians, researchers and activists.Methods: In-depth interviews were conducted on a purposive sample of fourteen key informants in South Africa. Audiotaped interviews were transcribed verbatim with concurrent thematic analysis. The perspectives of HIV clinicians, researchers and activists were captured. Analyst triangulation occurred as the data were analysed by three authors independently.Results: The rapid evolution of HIV cure research agendas was prominent with participants expressing some concern that the global North was driving the cure agenda. Participants described a symbiotic relationship between cure, treatment and prevention research necessitating collaboration. Assessing and managing knowledge and expectations around HIV cure research emerged as a central theme related to challenges to constructing 'cure' - how patients understand the idea of cure is important in explaining the complexity of cure research especially in the South African context where understanding of science is often challenging. Managing expectations and avoiding curative misconception will have implications for consent processes. Unique strategies in cure research could include treatment interruption, which has the potential to create therapeutic and ethical conflict and will be perceived as a significant risk. Ethical challenges in cure research will impact on informed consent and community engagement.Conclusions: It was encouraging to note the desire for synergy amongst researchers and clinicians working in the fields of prevention, treatment and cure. Translation of complex HIV cure science into lay language is critical. Moving forward, RECs must be adequately constituted with scientific expertise and community representation when reviewing cure protocols. It is hoped that knowledge and resource sharing in the context of collaboration between research scientists working in cure and those working in treatment and prevention will accelerate progress towards cure. [ABSTRACT FROM AUTHOR]

Innovative strategies for HIV cure are in development and research studies are being designed and planned globally. South Africa is no exception. However, little is known about stakeholders’ knowledge, understanding and expectations of future cure research. This study aimed to obtain in-depth qualitative insights into stakeholder perspectives at this formative stage of HIV cure research. Fifteen stakeholders were interviewed in an HIV research clinic in the Western Cape, South Africa with their consent. Interviews were transcribed verbatim and analysed using thematic content analysis. Broad themes that emerged included the meaning of cure, awareness of HIV cure research, risks and benefits of such research. General awareness and understanding of HIV cure research was lower than expected. Some participants expressed a fatalistic attitude to HIV and described it as an “end-time illness” with no prospect of cure. In general, HIV cure research was regarded as risky – biologically psychologically and socially. If study designs were to include treatment interruption, participants would comply only if success was guaranteed. Given these perceptions of HIV cure research, significant challenges to consent processes and participant recruitment can be anticipated. Authentic community engagement and intensive educational interventions will be necessary prior to future cure research in South Africa. [ABSTRACT FROM PUBLISHER]

The article reports the experiments conducted on Young Men who have Sex with Men's(YMSM) likelihood of using rectal microbicide gel and applicator. An ethinically diverse sample was chosen and asked to insert hydroxyethylcellulose(HEC) placebo gel rectally before repetitive anal intercourse(RAI) to report the procuct's acceptability regards applicator, side effects and sexual satisfaction. Positive indications for satisfacory usage were percieved.

Protein microbicides against HIV can help to prevent infection but they are required in large, repetitive doses. This makes current fermenter-based production systems prohibitively expensive. Plants are advantageous as production platforms because they offer a safe, economical and scalable alternative, and cereals such as rice are particularly attractive because they could allow pharmaceutical proteins to be produced economically and on a large scale in developing countries. Pharmaceutical proteins can also be stored as unprocessed seed, circumventing the need for a cold chain. Here, we report the development of transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was predominantly aglycosylated. Nevertheless, the heavy and light chains assembled into functional antibodies with more potent HIV-neutralizing activity than other plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type glycans. Immunolocalization experiments showed that the assembled antibody accumulated predominantly in protein storage vacuoles but also induced the formation of novel, spherical storage compartments surrounded by ribosomes indicating that they originated from the endoplasmic reticulum. The comparison of wild-type and transgenic plants at the transcriptomic and proteomic levels indicated that endogenous genes related to starch biosynthesis were downregulated in the endosperm of the transgenic plants, whereas genes encoding prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into factors that affect the functional efficacy of neutralizing antibodies in plants and the impact of recombinant proteins on endogenous gene expression. [ABSTRACT FROM AUTHOR]