Brief Report: Dipyridamole Decreases Gut Mucosal Regulatory T-Cell Frequencies Among People With HIV on Antiretroviral Therapy.

BACKGROUND: We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine levels. METHODS: In this substudy, rectosigmoid biopsies were obtained from 18 participants (9 per arm), to determine whether 12 weeks of dipyridamole affects mucosal immune cells. Participants randomized to placebo were then switched to dipyridamole for 12 weeks while the treatment arm continued dipyridamole for another 12 weeks. We evaluated T-cell frequencies and plasma markers of microbial translocation and intestinal epithelial integrity. Linear regression models on log-transformed outcomes were used for the primary 12-week analysis. RESULTS: Participants receiving dipyridamole had a median 70.2% decrease from baseline in regulatory T cells (P = 0.007) and an 11.3% increase in CD8 T cells (P = 0.05). There was a nonsignificant 10.80% decrease in plasma intestinal fatty acid binding protein levels in the dipyridamole arm compared with a 9.51% increase in the placebo arm. There were no significant differences in plasma levels of ß-D-glucan. In pooled analyses, there continued to be a significant decrease in regulatory T cells (-44%; P = 0.004). There was also a trend for decreased CD4 and CD8 T-cell activation. CONCLUSION: Increasing extracellular adenosine levels using dipyridamole in virally suppressed HIV (+) individuals on antiretroviral therapy can affect regulation of gut mucosal immunity.

Prevalence and determinants of anal human papillomavirus infection in men who have sex with men and transgender women.

Human papillomavirus (HPV) prevalence varies by population. This study investigated anal HPV type detection risk by country in a population of men who have sex with men (MSM) and transgender women (TW) at risk of HIV. Sexually active HIV-1-uninfected MSM and TW were enrolled at eight sites: four in the United States (US), two in Thailand, one in Peru, and one in South Africa. Baseline anal HPV swabs were collected, and DNA typing was performed. One hundred and ninety-five participants, 76 (42%) from the US, had a mean age of 30.9 years (range 18-64). In 182 participants with results available, anal HPV infection was common with 169 (93%) with ≥1 type, 132 (73%) with ≥1 nine-valent vaccine types, and 66 (36%) with HPV 16. Participants in the US had a higher prevalence of HPV 16 (56%, p = 0.004) and HPV 6 (69%, p < 0.001) compared to the other regions. Stimulant drug use was significantly associated with HPV 6 detection. Anal HPV is highly prevalent in this population of MSM and TW sampled from four countries, with HPV 16 the most commonly detected type. The nine-valent HPV vaccine has the potential to provide significant protection if given prior to exposure.

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.

Influence of Partner Type on Acceptability and Likelihood of Use of a Rectal Microbicide Among Young Men Who Have Sex With Men in the United States and Puerto Rico.

This study examined how acceptability of placebo gel with receptive anal intercourse (RAI) and likelihood of future rectal microbicide use varied across partner types. Because no rectal microbicide is available yet, use of placebo permitted the study of gel use behavior in real-life circumstances. A total of 87 men who have sex with men (MSM) aged 18 to 30 years inserted placebo gel rectally before RAI during 12 weeks. Using mixed-methods design, participants completed a behavioral questionnaire and in-depth interview. In all, 62 men (71.3%) reported gel use with a lover (i.e., spouse equivalent, boyfriend), 32 (36.8%) with a one-night stand (i.e., man with whom you had sex once), and 29 (33.3%) with an "other" male partner. While gel acceptability was high across partner types, use with lovers was facilitated by trust and familiarity; yet trust made participants believe protection was less necessary. Conversely, participants expressed high likelihood of using gel with one-night stands, whom they perceived as riskier; yet they felt less comfortable discussing gel with them, often resorting to covert use or forgoing gel. A successful microbicide will be positioned as a sexual pleasure enhancer so that men can present it to their lovers and other partners as a gel that improves sex and secondarily prevents human immunodeficiency virus (HIV).

Awareness of Post-Exposure Prophylaxis (PEP) and Pre-Exposure Prophylaxis (PrEP) Is Low but Interest Is High Among Men Engaging in Condomless Anal Sex With Men in Boston, Pittsburgh, and San Juan.

This study examines awareness of and experiences with post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP) among 228 men recruited in Boston, Pittsburgh, and San Juan between 12/2010 and 6/2012. All of them reported having condomless anal sex with a man in the prior year. Overall, 41% had heard of PEP, ranging from 16% in San Juan to 64% in Boston. Only 21% had heard of PrEP, ranging from 8% in San Juan to 36% in Boston. Three had used PEP, and none had used PrEP. After the methods were described to participants, interest in both was high, with intentions to use PEP and PrEP respectively at 9.1 and 7.7 (10-point scale). Increased public education is needed to raise awareness of these HIV prevention methods, especially among MSM who acknowledge potential risk behavior. It also seems likely that many such men would use these methods once they become aware of them.

Rectal-specific microbicide applicator: evaluation and comparison with a vaginal applicator used rectally.

An applicator designed for rectal delivery of microbicides was tested for acceptability by 95 young men who have sex with men, who self-administered 4 mL of placebo gel prior to receptive anal intercourse over 90 days. Subsequently, 24 of the participants self-administered rectally 4 mL of tenofovir or placebo gel over 7 days using a vaginal applicator, and compared both applicators on a Likert scale of 1-10, with 10 the highest rating. Participants reported high likelihood to use either applicator in the future (mean scores 9.3 and 8.8 respectively, p = ns). Those who tested both liked the vaginal applicator significantly more than the rectal applicator (7.8 vs. 5.2, p = 0.003). Improvements in portability, conspicuousness, aesthetics, tip comfort, product assembly and packaging were suggested for both. This rectal-specific applicator was not superior to a vaginal applicator. While likelihood of future use is reportedly high, factors that decrease acceptability may erode product use over time in clinical trials. Further attention is needed to develop user-friendly, quick-acting rectal microbicide delivery systems.

The Motivations and Experiences of Young Women in a Microbicide Trial in the USA and Puerto Rico.

Young women are an important target group in microbicide research, yet little is known about why they participate and stay in microbicide trials. Our study examined motivations for participating in a Phase I microbicide trial among 61 women ages 18 - 24 years in the continental USA and Puerto Rico. We also examined their perspectives on study participation. Participants underwent a semi-structured in-depth interview in which they were asked about factors that motivated enrollment and their experiences while participating. They also completed a Web-based Computer Assisted Self Interview in which they were asked to rate study burden (1 = low to 4 = high). Factors that motivated enrollment were altruism (29%), compensation (17%), a combination of altruism and compensation (37%) and free medical exams (17%). Factors that encouraged participants to stay in the study were study staff (95%), confirmation of good health (41%), and the opportunity to learn about their bodies (17%). Mean ratings of study burden ranged from 1.83 (having to travel to site) to 2.41 (colposcopy), indicating that participants were not highly bothered by visits or procedures. Although Phase I trials require invasive procedures, participants were not highly bothered by them and recognized them as necessary. Good relationships with staff and clear information about how procedures contribute to study goals may encourage participants to remain in trials. Young women may be motivated to enter microbicide trials by stressing the role they will play in discovering better HIV-prevention methods and highlighting the comprehensive preventive exams they will receive.

"Tell Juliana": acceptability of the candidate microbicide VivaGel® and two placebo gels among ethnically diverse, sexually active young women participating in a phase 1 microbicide study.

This study assessed acceptability of the candidate microbicide VivaGel(®) and two placebo gels among 61 sexually active young US and Puerto Rican women at three sites. Participants were randomly assigned to use one of the gels twice per day for 14 days. At trial completion, 59% of the women in the VivaGel(®) group reported being likely to use the gel in the future, whereas 23% were unlikely to use it and 18% were undecided. Participants reported problems with all three gels, including the "universal" placebo containing hydroxyethyl cellulose (HEC). The most frequent complaints were leakage, interference with sexual behavior, and decreased sexual satisfaction. Some of the complaints are not new but remain unresolved. Women's perceived risk of HIV infection may determine whether the gels are used. Users also may want a choice of viscosity. Poor acceptability of vaginal microbicide formulations may result in poor adherence to gel use during efficacy trials and compromise validity of results.

Variations in microbicide gel acceptability among young women in the USA and Puerto Rico.

In a multi-site study of vaginal microbicide acceptability conducted with sexually active young women, quantitative assessments revealed significant differences in acceptability by site. Participants in Puerto Rico rated the gel more favourably than mainland US participants in terms of liking the gel and likelihood of future use. To explain these differences, we examined responses to qualitative behavioural assessments. Young women in mainland USA associated gel leakage with uncomfortable sensations experienced during menstruation, while young women in Puerto Rico had positive associations of gel use with douching. These negative or positive associations affected assessments of the gel's physical qualities. In addition, young women's perceptions of primary partners' support for microbicide use influenced sexual satisfaction with the gel and, ultimately, product acceptability. Finally, geographic HIV-risk context contributed to heightened HIV-risk perception, which influenced likelihood of future microbicide use, even for women in stated monogamous relationships. Future microbicide acceptability studies should take into account potential differences in acceptability by site such as HIV-risk perception based on local HIV prevalence, popularity of vaginal hygiene products in a specific area and male attitudes in different cultures concerning women's use of HIV protection strategies.