A latent trajectory analysis of young sexual and gender minorities' adherence to three rectal microbicide placebo formulations (MTN-035; a randomized crossover trial).

BACKGROUND: Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs). RM modalities may be beneficial for populations who have complex lifestyles, difficulties adhering to pre-exposure prophylaxis (PrEP) regimens, and/or have limited access to care. MTN-035 (DESIRE; Developing and Evaluating Short-Acting Innovations for Rectal Use), a randomized crossover trial, aimed to evaluate the safety and acceptability of, and adherence to, three placebo RM modalities (douche, insert, and suppository) prior to receptive anal intercourse. METHODS: We conducted latent trajectory analysis to identify clusters of individuals who shared similar trajectories in acceptability and adherence for each product (douche, insert, and suppository) over time. We analyzed weekly short messaging service (SMS) use reports for each modality as reported by enrolled sexual and gender minority (SGM) participants. RESULTS: Two trajectories for each product were identified: a "protocol compliant" trajectory (i.e., at least one product use occasion per week) and "high use" trajectory (i.e., more than three product use occasions per week). Participants with high use were more likely to lack access to PrEP and have higher intentions to utilize RM modalities compared to those who were protocol compliant. CONCLUSIONS: This study highlighted high adherence to RM modalities among SGM. As research into viable HIV prevention modalities continues to evolve, tailored intervention strategies are needed to support the uptake of and adherence to alternative prevention modalities that are behaviorally congruent with targeted users. TRIAL REGISTRATION: NCT03671239 (14/09/2018).

Patterns of a Rectal Microbicide Placebo Gel Use in a Preparatory Stage for a Phase I Trial Among Young Men Who Have Sex with Men.

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.

"Like Holding an Umbrella Before It Rains": Acceptability of Future Rectal Microbicides Among Men Who Have Sex With Men in India-A Modified Technology Acceptance Model.

Topical rectal microbicides (RMs) are a new prevention technology in development that aims to reduce the risk of HIV acquisition from anal sex. We examined RM acceptability among men who have sex with men (MSM) in India. We conducted a qualitative exploratory study guided by a modified Technology Acceptance Model, with 10 focus groups ( n = 61) of MSM and 10 key informant interviews. Data were explored using framework analysis. RM acceptability was influenced by technological contexts: perceived usefulness of RMs, perceived ease of use of RM and applicator, and habits around condom and lubricant use; individual and interpersonal contexts: perceived relevance and preferences for product formulation and dosing frequency; and MSM community/social contexts: perceived social approval, RM-related stigma, social support. Implementation of RMs for MSM in India may be supported by multi-level interventions that engage community-based organizations in destigmatizing and distributing RMs, ideally gel-based products that enable on-demand use before sex.

Acceptability of Three Novel HIV Prevention Methods Among Young Male and Transgender Female Sex Workers in Puerto Rico.

Sex workers need HIV-prevention methods they can control and incorporate easily in their work. We studied the acceptability of three methods: HIV self-test use with clients, oral pre-exposure prophylaxis (PrEP), and rectal microbicide gel. Four male and eight transgender female (TGF) sex workers in Puerto Rico completed a baseline survey with a quantitative measure of likelihood of use. From them, one male and four TGF also completed a 12-week study of rectal microbicide placebo gel use prior to receptive anal intercourse with male clients and evaluated via qualitative in-depth interviews and follow-up quantitative assessments how each method could be incorporated into their work. Most were interested in a rectal microbicide gel and able to use it covertly with clients. Challenges to using the HIV self-test with clients included the potential for both breach of confidentiality and confronting violent situations. Participants also expressed interest in oral PrEP, but raised concerns about side effects.

Prevalence and correlates of willingness to participate in a rectal microbicide trial among men who have sex with men in Bangkok.

Rectal microbicides (RMs) hold promise as a HIV prevention method to reduce transmission among men who have sex with men (MSM). To assess RM trial feasibility in Bangkok, we measured prevalence and correlates of willingness to participate among Thai MSM observational cohort participants. Between April 2006 and December 2010, 1744 MSM enrolled in the Bangkok MSM Cohort Study; at 12 months, RM trial participation willingness was measured. We evaluated correlates of RM trial participation willingness using logistic regression analysis. Participants completing the 12-month visit (81.4%, n = 1419) had a mean age of 27.3 years (SD = 6.1), and 65.5% and 86.1% reported having a steady partner or anal intercourse (AI) in the past four months, respectively. Most (79.1%, n = 1123) participants reported willingness to participate in an RM trial, which, in multivariable analysis, was independently associated with insertive only (adjusted odds ratio [AOR] = 3.25, 95% CI: 1.82-5.81) or receptive/versatile role AI (AOR = 3.07, 95% CI: 1.88-5.01), and being paid for sex (AOR = 12.15, 95% CI: 1.67-88.21) in the past four months, and believing that people with AIDS look sick (AOR = 1.92, 95% CI: 1.23-2.98). Of hypothetical RM trial features to increase enrollment likelihood, the most (91.1%) compelling was that the study be approved by the Thai ethics committee, followed by the study site offering evening hours (88.9%). Reasons not to participate were not wanting a rectal examination (29.5%) or fluid collected from the penis or anus (24.6%) and not wanting the placebo (23.0%). RM trial participation willingness was high, particularly for those with greater HIV acquisition risk, within this Thai MSM cohort, suggesting feasibility of an RM trial. Addressing potential barriers to trial entry may be useful in educational materials to optimize recruitment.

Examining the Safety, Pharmacokinetics, and Pharmacodynamics of a Rectally Administered IQP-0528 Gel for HIV Pre-Exposure Prophylaxis: A First-In-Human Study.

A lubricating microbicide gel designed for rectal and vaginal use would provide a behaviorally congruent strategy to enhance pre-exposure prophylaxis adherence and reduce HIV infection risk. In this study, we report the first-in-human evaluation of such a gel containing 1% IQP-0528, an investigational antiretroviral. Seven HIV-1-negative participants received one 10 mL rectal dose of radiolabeled 1% IQP-0528 gel. We assessed safety; IQP-0528 pharmacokinetics in plasma, and rectal and vaginal tissue; ex vivo local pharmacodynamics (PD); and colorectal distribution. The 1% gel was determined to be safe with one mild event attributed to study product and no effects on rectal tissue histology. All concentrations measured in plasma and vaginal tissue were below the limit of quantitation. Median IQP-0528 concentrations in rectal tissue exceeded the in vitro EC95 against HIV-1 (0.07 ng/mg) by 3-5 h of dosing and remained above this concentration for at least 24 h, despite a 3-log reduction in concentration over this duration of time. Rectal tissue PD-assessed by ex vivo HIV challenge-demonstrated significant p24 antigen reduction 3-5 h postdose compared with baseline (p = .05), but not 24-26 h postdose (p = .75). Single-photon emission computed tomography/computed tomography imaging revealed that product distribution was localized to the rectosigmoid. The IQP-0528 gel possesses desirable features for a topical microbicide including: local safety with no systemic absorption, delivery of locally high IQP-0528 concentrations, and significant reductions in ex vivo HIV infectivity. However, the gel is limited by its rapid clearance and inability to penetrate vaginal tissues following rectal dosing. Clinical Trial Registration number: NCT03082690.

Development, Characterization and In Vivo Pharmacokinetic Assessment of Rectal Suppositories Containing Combination Antiretroviral Drugs for HIV Prevention.

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development.

A social ecology of rectal microbicide acceptability among young men who have sex with men and transgender women in Thailand.

INTRODUCTION: With HIV-incidence among men who have sex with men (MSM) in Bangkok among the highest in the world, a topical rectal microbicide would be a tremendous asset to prevention. Nevertheless, ubiquitous gaps between clinical trial efficacy and real-world effectiveness of existing HIV preventive interventions highlight the need to address multi-level factors that may impact on rectal microbicide implementation. We explored the social ecology of rectal microbicide acceptability among MSM and transgender women in Chiang Mai and Pattaya, Thailand. METHODS: We used a qualitative approach guided by a social ecological model. Five focus groups were conducted in Thai using a semi-structured interview guide. All interviews were digitally recorded, transcribed verbatim in Thai and translated into English. We conducted thematic analysis using line-by-line and axial coding and a constant comparative method. Transcripts and codes were uploaded into a customized database programmed in Microsoft Access. We then used content analysis to calculate theme frequencies by group, and Chi-square tests and Fisher's exact test to compare themes by sexual orientation/gender expression and age. RESULTS: Participant's (n=37) mean age was 24.8 years (SD=4.2). The majority (70.3%) self-identified as gay, 24.3% transgender women. Product-level themes (side effects, formulation, efficacy, scent, etc.) accounted for 42%, individual (increased sexual risk, packaging/portability, timing/duration of protection) 29%, interpersonal (trust/communication, power/negotiation, stealth) 8% and social-structural (cost, access, community influence, stigma) 21% of total codes, with significant differences by sexual orientation/gender identity. The intersections of multi-level influences included product formulation and timing of use preferences contingent on interpersonal communication and partner type, in the context of constraints posed by stigma, venues for access and cost. DISCUSSION: The intersecting influence of multi-level factors on rectal microbicide acceptability suggests that social-structural interventions to ensure widespread access, low cost and to mitigate stigma and discrimination against gay and other MSM and transgender women in the Thai health care system and broader society will support the effectiveness of rectal microbicides, in combination with other prevention technologies, in reducing HIV transmission. Education, outreach and small-group interventions that acknowledge differences between MSM and transgender women may support rectal microbicide implementation among most-at-risk populations in Thailand.