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)

Abstract

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.

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

“…Two hundred and seventeen HIV‐negative transgender men, transgender women and cisgender MSM between the ages of 18 and 35 were recruited into the trial [ 24 ]. Data collection took place between April 2019 and July 2020 in Malawi (Blantyre), Peru (Lima), South Africa (Johannesburg), Thailand (Chiang Mai) and the United States (Pittsburgh, Pennsylvania; Birmingham, Alabama; and San Francisco, California).…”

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

“…The eligibility criteria for this study encompassed the following: 1) men (cis or transgender) and transgender women between 18–35 years old; 2) HIV-1 or HIV-2 uninfected at Screening and Enrollment; 3) in general good health at Screening and Enrollment (e.g., medical and medication history, physical exam including a rectal exam); 4) a reported history of consensual RAI at least three times in the past three months and expectation to maintain at least that frequency of RAI during study participation; 5) For individuals who could get pregnant (transgender men with a female reproductive system), a negative pregnancy test at Screening and Enrollment; 6) For individuals who could get pregnant, use of an effective method of contraception for at least 30 days (inclusive) prior to Enrollment, and intention to use an effective method for the duration of study participation; 7) ability and willingness to provide written informed consent in local language; 8) ability and willingness to provide adequate locator information; 9) availability to return for all study visits and willingness to comply with study participation requirements;10) willingness to not take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation [ 19 ]. Participants who met any of the following criteria were excluded from the study: 1) a history of inflammatory bowel disease or anorectal condition that would hinder the placement or assessment of product tolerability; 2) anticipated use of non-study rectally administered products; 3) prior participation in research studies involving rectal products; 4) presence of an active anorectal or reproductive tract infection requiring treatment; 5) symptomatic urinary tract infection (participants with these conditions could be retested during screening and potentially enrolled if resolved); 6) pregnancy or breastfeeding.…”

“…Condoms and lubricant were dispensed to participants during all clinic visits, and they also received HIV/STI risk reduction counseling at screening, enrollment, and during study visits. Consented and enrolled participants were then randomized into one of six sequences, each varying the order in which participants used the study placebo products, with a 1-week wash-out period between each 4-week product use period [ 19 ] (Table 1 ).…”

“…A visit was considered to be missed if the participant did not complete any portion of it within the designated visit window. However, if an interim visit was conducted to compensate for the missed regular visit, then the missed regular visit was counted as completed [ 19 ].…”

Preclinical and Early Clinical Development of Tenofovir Alafenamide/Elvitegravir Topical Inserts for Effective On-Demand Vaginal and Rectal HIV Prevention

“…It should be noted that while short-term use was listed as a negative attribute, overall, the on-demand products (insert, film, and gel) were most liked. These inserts were also included as one of the three placebo products (insert, suppository, enema) evaluated for rectal use prior to receptive anal intercourse (RAI) for the prevention of HIV in MTN-035 (NCT03671239), a randomized crossover trial for assessment of safety, acceptability, and adherence [36]. Participants (n = 217) included HIV-uninfected transgender men, transgender women, and cisgender MSM from five different countries (Malawi, Peru, South Africa, Thailand, and the U.S.).…”