History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products.

The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.

RESUMEN: El estudio DESIRE (MTN-035) exploró la preferencia de producto entre tres formulaciones de microbicida rectal (MR) de placebo, una ducha rectal, un supositorio y un inserto, entre 210 personas transgénero y hombres que tienen sexo con hombres en cinco países: los Estados Unidos, Perú., Tailandia, Sudáfrica y Malawi. Los participantes utilizaron cada producto antes del sexo anal receptive (SAR) durante un mes, siguiendo una secuencia asignada al azar, luego seleccionaron su producto preferido mediante una autoentrevista asistida por computadora. Las entrevistas en profundidad examinaron los motivos de preferencia. Comparamos la preferencia de producto y el uso previo del producto por país para explorar si la ubicación geográfica y la experiencia con la forma farmacéutica impactaron la preferencia. Una mayoría en los Estados Unidos (56%) y Perú (58%) y casi la mitad en Sudáfrica (48%) prefirieron la ducha rectal. La mayoría en Malawi (59%) prefirió el supositorio, mientras que la mitad en Tailandia (50%) y casi la mitad en Sudáfrica (47%) prefirió el inserto. Los participantes que prefirieron la ducha rectal la describieron como rápida y fácil, ya parte de su rutina y que tenía el doble propósito de limpiar y proteger. Los que prefirieron el inserto lo consideraron pequeño, portátil, discreto y de rápida disolución. Los que prefirieron el supositorio encontraron que tenía un tamaño y forma aceptables y proveía lubricación adicional. La experiencia con el uso del producto varió según el país. Los participantes con experiencia con duchas rectales tenían significativamente más probabilidades de preferir la ducha rectal (p = 0,03). Diversificar la disponibilidad de múltiples formas farmacéuticas de MR puede aumentar la aceptación y mejorar los esfuerzos de prevención del VIH a nivel mundial.

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).

Acceptability of a Dapivirine/Placebo Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-026).

This study describes the acceptability of a rectal microbicide gel formulation using dapivirine (DPV) among men and women from two countries (United States and Thailand) participating in the Microbicide Trials Network-026 trial. We evaluated participants' acceptability of a rectal DPV/placebo gel as part of a Phase I trial (N = 26; 18 male, 8 female). Participants reported favorable acceptability of the study gel, with most participants reporting that they liked the gel the same (n = 14; 53.8%) or more (n = 11; 42.4%) than when they started the trial. Over half of participants noted that they would prefer the gel over condoms (n = 13; 50%) or that they liked condoms and the gel equally (n = 8; 30.8%). Side effects across products included leakage (n = 8; 30.8%), diarrhea (n = 4; 15.4%), or soiling (n = 1; 3.8%). The high acceptability of a rectal gel underscores its promise as a short-acting biomedical prevention, warranting future research for HIV prevention.Trial Registration: NCT03239483.

RESUMEN: Este estudio describe la aceptabilidad de un microbicida rectal (RM) con dapivirina (DPV) formulado como un gel por hombres y mujeres de dos países (Estados Unidos y Tailandia) que participaron como parte del Microbicide Trials Network (MTN)-026. Evaluamos la aceptabilidad de un gel rectal de DPV y un placebo como parte de un estudio de Fase I (N = 26; 18 hombres, 8 mujeres). Los participants informaron una aceptabilidad favorable sobre el gel del estudio; la mayoría de los participantes informaron que les gustó el gel igual (n = 14; 53.8%) o más (n = 11; 42.4%) que cuando comenzaron el estudio. Más de la mitad de los participantes señalaron que preferirían el gel sobre los condones (n = 13; 50%) o que les gustaban los condones y el gel por igual (n = 8; 30,8%). Los efectos de los productos incluyeron fugas (n = 8; 30,8%), diarrea (n = 4; 15,4%) o ensuciamiento (n = 1; 3,8%). La alta aceptabilidad de un gel rectal enfatiza su promesa para la prevención biomédica de acción corta y justifica futuras investigaciones para la prevención del VIH.

Rectal Douching and Microbicide Acceptability among Young Men who Have Sex with Men.

Men who have sex with men (MSM) commonly report engaging in rectal douching (RD) practices prior to receptive anal intercourse. Researchers are interested in the possibility of designing a RD with a microbicide component. In our analyses, we examined whether YMSM who engaged in RD behaviors differ in HIV prevention behaviors from their non-RD peers. We then examined whether RD frequency was associated with rectal microbicide acceptability. Half the participants (47.8%) reported having ever douched. Participants were more likely to douche if they were racial/ethnic minorities (AOR = 2.24, p = 0.02) and had recently tested for HIV (AOR = 1.96, p = 0.04). Greater douching frequency was associated with racial/ethnic minorities (ß = 0.20, p = 0.009) and recent HIV testing (ß = 0.19, p < 0.01). Participants who reported frequently douching indicated greater microbicide acceptability (ß = 0.32, p < 0.001). Designing behaviorally congruent products remains a priority in next generation Pre-Exposure Prophylaxis (PrEP) and a rectal douche might be an additional tool if found to be efficacious.

Acceptability and Preliminary Efficacy of an Online HIV Prevention Intervention for Single Young Men Who Have Sex with Men Seeking Partners Online: The myDEx Project.

Prevention of new cases of HIV among young gay, bisexual and other men who have sex with men (YGBMSM; ages 18-24) remains a priority. We developed and pilot tested an online intervention (myDEx) using a pilot randomized trial design with 180 online-recruited single YGBMSM who reported recent unprotected anal intercourse, self-reporting as HIV negative or status-unaware, and who met sexual partners through online dating applications. myDEx participants reported higher overall satisfaction (d = 0.46) and willingness to recommend the intervention to friends (d = 0.48) than controls. myDEx participants were less likely to report foregoing condoms to achieve an emotional connection with a partner (d =0 .43), and more likely to report greater emotional regulation during their partner-seeking behaviors (d = 0.44). myDEx participants reported fewer partners with whom they had condomless receptive anal sex (d = 0.48). Our pilot results demonstrate the potential of the myDEx intervention, suggesting that a larger efficacy trial may be warranted in the future.

Applying resilience theory models to contextualize economic-dependent partnerships as a risk factor for HIV among young men who have sex with men.

Economic-dependent partnerships (EDP) are an understudied HIV risk correlate among young men who have sex with men (YMSM) in the U.S. We explored whether YMSM's psychological resilience buffered against the effect of socioeconomic disadvantage on EDPs, after accounting for other psychosocial risks. Data come from an observational study assessing YMSM's HIV vulnerabilities. We developed indices for socioeconomic disadvantage, psychosocial profiles, and cumulative promotive factors. Multivariable logistic regressions tested the main associations of these indices on EDPs. Protective models tested whether psychosocial profiles exacerbated and cumulative promotive factors buffered the effects of socioeconomic disadvantage on EDPs. 31% and 23% of YMSM reported EDPs with main and casual partners, respectively. For both outcomes, we found support for adjusted compensatory models. Socioeconomic disadvantage was associated with increased odds of EDPs with main (AOR = 1.45, p < .001) and casual (AOR = 1.47, p < .001) partners. Psychosocial profiles were also associated with increased odds of EDPs with main (AOR = 1.53, p = .001) and casual (AOR = 1.67, p < .001) partners. Cumulative promotive factors was associated with decreased odds of EDPs with main (AOR = 0.66, p = .003) and casual (AOR = 0.72, p = .035) partners. Our findings elucidate the need for multilevel interventions that provide opportunities for socioeconomic advancement and improve psychosocial/psychological functioning for at-risk YMSM.

A conjoint experiment of three placebo rectal products used with receptive anal sex: results from MTN-035.

INTRODUCTION: End-user perspectives are vital to the design of new biomedical HIV prevention products. Conjoint analysis can support the integration of end-user perspectives by examining their preferences of potential pre-exposure prophylaxis (PrEP) products. The Microbicides Trial Network (MTN) 035 protocol examined three placebo rectal dosage forms (insert, enema and suppository) that could deliver PrEP prior to receptive anal sex (RAS). METHODS: Between April 2019 and July 2020, we enrolled 217 HIV-negative, cisgender men who have sex with men (MSM; n = 172; 79.3%) and transgender people (n = 47; 20.7%) ages 18-35 into a randomized cross-over trial across Malawi, Peru, South Africa, Thailand and the United States. Participants used each product prior to RAS over 4-week periods. Participants completed a conjoint experiment where they selected between random profiles using seven features (dosage form, timing of use before sex, side effects, duration of protection, effectiveness, frequency of use and need for a prescription). RESULTS: Effectiveness was the strongest determinant of choice (30.4%), followed by modality (18.0%), potential side effects (17.2%), frequency of use (10.8%), duration of protection (10.4%), timing of use before sex (7.4%) and need for a prescription (5.9%). Relative utility scores indicated that the most desirable combination of attributes was a product with 95% efficacy, used 30 minutes before sex, offering a 3- to 5-day protection window, used weekly, having no side effects, in the form of an enema and available over-the-counter. CONCLUSIONS: Choice in next-generation PrEP products is highly desired by MSM and transgender people, as no one-size-fits-all approach satisfies all the preferences. MTN-035 participants weighed product features differently, recognizing the need for diverse, behaviourally congruent biomedical options that fit the needs of intended end-users.

A randomized trial of safety, acceptability and adherence of three rectal microbicide placebo formulations among young sexual and gender minorities who engage in receptive anal intercourse (MTN-035).

Efforts to develop a range of HIV prevention products that can serve as behaviorally congruent viable alternatives to consistent condom use and oral pre-exposure prophylaxis (PrEP) remain crucial. MTN-035 was a randomized crossover trial seeking to evaluate the safety, acceptability, and adherence to three placebo modalities (insert, suppository, enema) prior to receptive anal intercourse (RAI). If participants had no RAI in a week, they were asked to use their assigned product without sex. We hypothesized that the modalities would be acceptable and safe for use prior to RAI, and that participants would report high adherence given their behavioral congruence with cleansing practices (e.g., douches and/or enemas) and their existing use to deliver medications (e.g., suppositories; fast-dissolving inserts) via the rectum. Participants (N = 217) were sexual and gender minorities enrolled in five different countries (Malawi, Peru, South Africa, Thailand, and the United States of America). Mean age was 24.9 years (range 18-35 years). 204 adverse events were reported by 98 participants (45.2%); 37 (18.1%) were deemed related to the study products. The proportion of participants reporting "high acceptability" was 72% (95%CI: 65% - 78%) for inserts, 66% (95%CI: 59% - 73%) for suppositories, and 73% (95%CI: 66% - 79%) for enemas. The proportion of participants reporting fully adherent per protocol (i.e., at least one use per week) was 75% (95%CI: 69% - 81%) for inserts, 74% (95%CI: 68% - 80%) for suppositories, and 83% (95%CI: 77% - 88%) for enemas. Participants fully adherent per RAI-act was similar among the three products: insert (n = 99; 58.9%), suppository (n = 101; 58.0%) and enema (n = 107; 58.8%). The efficacy and effectiveness of emerging HIV prevention drug depends on safe and acceptable delivery modalities that are easy to use consistently. Our findings demonstrate the safety and acceptability of, and adherence to, enemas, inserts, and suppositories as potential modalities through which to deliver a rectal microbicide.

Acceptability of PC-1005 Gel Administered Rectally to HIV-1 Seronegative Adults at Three Different Volume Levels (MTN-037).

Multipurpose prevention technologies (MPT) have been increasingly researched for their dual-purpose preventative properties against HIV and other STIs. The acceptability of PC-1005, a topical MPT candidate, was explored among men and women participating in the MTN-037 Phase I trial at two U.S. sites (Pittsburgh, PA, and Birmingham, AL). We triangulated quantitative and qualitative assessments of the acceptability of three volumes (4 mL, 16 mL, 32 mL) of PC-1005 administered rectally (N = 12; 6 males, 6 females). Participants rated overall gel acceptability on a scale of 1-10, with a median of 7.17 (SD = 2.04) and had positive feelings about all three dose volumes, citing them to be very comfortable or comfortable (dose 1 = 91.7%; dose 2 = 91.7%; dose 3 = 83.3%). High acceptability of and comfort with all three dose volumes shows promise for PC-1005 as an MPT to prevent HIV and STIs, warranting future clinical development.

Acceptability of a Dapivirine Gel Administered Rectally to HIV-1 Seronegative Adults (MTN-033 Study).

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.

Young men who have sex with men's awareness, acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study.

BACKGROUND: New cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM's vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research. METHODS: This secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI.We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses. RESULTS: Acceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (ß = 0.62) and 85% (ß = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (ß = -0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (ß = 0.18) and altruism (ß = 0.60), and negatively associated with education (ß = -0.21). CONCLUSIONS: YMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns. ClinicalTrials.gov Identifier: NCT02842060.

Development of a Tailored HIV Prevention Intervention for Single Young Men Who Have Sex With Men Who Meet Partners Online: Protocol for the myDEx Project.

BACKGROUND: New cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM), aged 18 to 24, underscore the importance of developmentally-informed HIV programs for YMSM. We developed an online intervention focused on risk reduction strategies across different sexual partner types. Intervention activities focus on assisting YMSM reflect on their partner-seeking behaviors, develop sexual decision-making rules to reduce their HIV risks, and consider the adoption of HIV prevention behaviors. OBJECTIVE: This pilot, randomized controlled trial (RCT) aims to examine the feasibility, acceptability, and preliminary efficacy of a tailored, Web-based HIV prevention intervention for single YMSM. METHODS: We designed a prospective RCT of online-recruited cis-gender men (N=180) who reported recent unprotected anal intercourse, self-report as HIV negative or are unaware of their HIV status, and meet sexual partners through online dating apps. Individuals in the control arm receive an attention-control condition that includes HIV/sexually transmitted infection (STI) information currently available on sex education websites. Individuals in the intervention arm receive a 6-session Web-based program tailored on their demographic information, partner-seeking behaviors and relationship desires, and prior sexual attitudes and behaviors. This tailored content will match HIV prevention messages and safer sex skills with YMSM's outcome expectancies when meeting new partners and thereby help them consider how to integrate safer sex practices into different partner types. Study assessments are taken at baseline, 30-, 60-, and 90-day follow-ups. Intervention acceptability and preliminary efficacy will be explored in sexual risk behaviors and HIV/STI testing. RESULTS: The RCT launched in November 2016 and is ongoing. To date, 180 eligible individuals have been enrolled, consented, and randomized. Of the 120 individuals in the intervention arm, 51.7% (62/120) identify as non-Hispanic white and half of the control arm identifies as non-Hispanic white. There were no differences observed by arm for race and/or ethnicity, age, or sexual orientation. CONCLUSIONS: Although there are in-person evidence-based interventions with proven efficacy for YMSM, few HIV/STI prevention interventions delivered online exist. Online interventions may ease access to comprehensive HIV/STI education among YMSM and allow personalized content to be delivered. The online intervention that we developed, myDEx, aims to alleviate the gaps within HIV prevention for YMSM by utilizing tailored, Web-based content with the goal of developing skills for same-sex dating and relationship building, while reducing their risks for HIV/STI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02842060; https://clinicaltrials.gov/ct2/show/NCT02842060 (Archived by WebCite at http://www.webcitation.org/6rcJdxF9v).