High prevalence of rectal chlamydia among pregnant adolescents in La Romana, Dominican Republic warrants extragenital STI testing

To our knowledge, there are no studies estimating the prevalence of extragenital sexually transmitted infections (STIs) among pregnant adolescents in the Caribbean. This study sought to fill this gap by assessing the prevalence and correlates of oral, genital, and rectal chlamydia (CT) among a sample of pregnant adolescents in La Romana, Dominican Republic. Two hundred pregnant youths, aged 15–24 years, were recruited by systematic sampling during their first prenatal visit to a maternal care unit. A sociodemographic and behavioral questionnaire was administered and urine and oral/anal swabs were collected and tested for CT. Descriptive analyses and Fisher’s exact tests were performed. The prevalence of oral, genital, and rectal CT was 6%, 15%, and 23%, respectively, although less than 5% of participants reported ever engaging in receptive anal intercourse. This discrepancy could be explained by autoinoculation, concurrent transmission during sex, undertreatment of rectal CT, or underreporting of anal sex. Almost half of CT infections would have been missed if only genital samples were collected, as current protocol dictates. More research is needed to understand sexual behaviors and rectal STI risk factors among heterosexual adolescent women. STI screening procedures for pregnant and sexually active adolescents should include routine testing of extragenital sites.

Prevalence of Anal Intraepithelial Lesions in Patients with Inflammatory Bowel Disease

Introduction Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal canal associated with HPV, with a higher prevalence in immunosuppressed individuals. Patients with inflammatory bowel disease (IBD) are at potential risk for their development, due to the use of immunosuppressants and certain characteristics of the disease. Method This is a prospective, cross-sectional, and interventional study that included 53 patients with IBD treated at a tertiary outpatient clinic, who underwent anal smear for cytology in order to assess the prevalence of AIN and associated risk factors. Results Forty-eight samples were negative for dysplasia and 2 were positive (4%). Both positive samples occurred in women, with Crohn's disease (CD), who were immunosuppressed and had a history of receptive anal intercourse. Discussion The prevalence of anal dysplasia in IBD patients in this study is similar to that described in low-risk populations. Literature data are scarce and conflicting and there is no evidence to recommend screening with routine anal cytology in patients with IBD. Female gender, history of receptive anal intercourse, immunosuppression and CD seem to be risk factors.

Improved PrEP Awareness and Use among Trans Women in San Francisco, California

Transgender women face a serious risk of HIV infection. Despite this, there is limited knowledge and use of Pre-exposure prophylaxis (PrEP). We measured the continuity of prevention across services in the PrEP cascade and correlates of PrEP use among trans women in San Francisco enrolled in the 2019/20 National HIV Behavioral Surveillance Study. Knowledge and use of PrEP among trans women in San Francisco increased in recent years; almost all (94.0%) had heard about PrEP, 64.7% had discussed PrEP with a healthcare provider, and 44.8% had taken PrEP in the past 12 months. PrEP use was associated with participation in a PrEP demonstration project (aOR = 31.44, p = 0.001) and condomless receptive anal intercourse (aOR = 3.63, p = 0.024). Injection drug use was negatively associated (aOR = 0.19, p = 0.014). Efforts are needed to combat the gender-based stigma and discrimination faced by trans women, which can result in avoidance and mistrust of the medical system.

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.

Th17 T cells and immature dendritic cells are the preferential initial targets after rectal challenge with an SIV-based replication-defective dual-reporter vector

Understanding the earliest events of HIV sexual transmission is critical to develop and optimize HIV prevention strategies. To gain insights into the earliest steps of HIV rectal transmission, including cellular targets, rhesus macaques were intra-rectally challenged with a single-round SIV-based dual reporter that expresses luciferase and iRFP670 upon productive transduction. The vector was pseudotyped with the HIV-1 envelope JRFL. Regions of tissue containing foci of luminescent, transduced cells were identified macroscopically using an in vivo imaging system, and individual transduced cells expressing fluorescent protein were identified and phenotyped microscopically. This system revealed that anal and rectal tissues are both susceptible to transduction 48 hours after the rectal challenge. Detailed phenotypic analysis revealed that on average, 62% of transduced cells are CCR6 + T cells—the vast majority of which express RORγT, a Th17 lineage-specific transcription factor. The second most common target cells were immature dendritic cells at 20%. These two cell types were transduced at the rates that are four to five times higher than their relative abundances indicate. Our work demonstrates that Th17 T and immature dendritic cells are preferential initial targets of HIV/SIV rectal transmission. IMPORTANCE Men and women who participate in unprotected receptive anal intercourse are at high risk for acquiring HIV. While in vitro data have developed a framework for understanding HIV cell tropism, the initial target cells in the rectal mucosa have not been identified. In this study, we identify these early host cells by using an innovative rhesus macaque rectal challenge model and methodology, which we previously developed. Thus, by shedding light on these early HIV/SIV transmission events, this study provides a specific cellular target for future prevention strategies.

Efficacy of a carrageenan gel in preventing anal human papillomavirus (HPV) infection: interim analysis of the Lubricant Investigation in Men to Inhibit Transmission of HPV Infection (LIMIT-HPV) randomised controlled trial

BackgroundCarrageenan, a non-toxic gelling agent derived from red algae, has potent anti-human papillomavirus (HPV) activity in in vitro and animal studies. We assessed, in an interim analysis, the efficacy of a carrageenan-based gel in reducing the risk of new detections of anal HPV among gay, bisexual and other men who have sex with men (gbMSM).MethodsThe LIMIT-HPV study (Lubricant Investigation in Men to Inhibit Transmission of HPV Infection) is a phase IIb, double-blind, placebo-controlled randomised controlled trial conducted in Montreal, Canada. gbMSM were randomly assigned (1:1) to receive a carrageenan-based or placebo gel. Participants were instructed to apply the gel to the anus, condom and/or partners’ penis before and—as required—during receptive anal intercourse. Questionnaire data and anal samples were collected at 0, 1, 2, 3, 6, 9 and 12 months. We estimated new detections of anal HPV infection(s) detected via Linear Array using Cox proportional hazards models.ResultsParticipants recruited from February 2016 to December 2019 were randomly assigned to the carrageenan (n=127) or placebo (n=128) arm. The efficacy and safety analyses included 201 and 210 participants. The median follow-up time was 7.6 months (range: 0–28.5) in the carrageenan group and 9.3 months (range: 0–40.7) in the placebo group. The HR for new detections was 1.21 (95% CI 0.86 to 1.70): 69.4% and 65.1% new detections of HPV in the carrageenan and placebo arms, respectively. More adverse events were reported in the carrageenan (59.8%) compared with the placebo (39.8%) arm.ConclusionsThe interim analysis did not demonstrate a protective effect of carrageenan on the risk of new detections of anal HPV infection among gbMSM. Carrageenan gel use was associated with a higher proportion of adverse events. Given these findings and the (assumed) low probability that a beneficial effect would be found by the study’s end, the trial was terminated as recommended by the Data Safety and Monitoring Board.Trial registration numberNCT02354144.

The Psycho-Social and Socio-Cultural Factors of Crystal Methamphetamine Use Among the Gay, Bi and MSM (GBM) Population

In the United States, men who have sex with men (MSM) remain as the demographic group with the highest HIV incidence rates and account for 53% of new HIV infections in 2006 (Rajasingham, Mimiaga, White, Pinkston, Baden, & Mitty, 2012). One of the reasons accounting for such high rates of HIV transmission between gay, bisexual and MSM (GBM) can be attributed to poly-substance use and the use of crystal methamphetamine (Solomon, Halkitis, Moeller, & Pappas, 2012; Rajasingham et al., 2012). The U.S. Centre for Disease Control and Prevention (2007) reported methamphetamine use in the MSM community is of particular concern due to the high prevalence of HIV and the use of the stimulant. Meanwhile, researchers have found methamphetamine use is closely corrleated to sexual risk taking among GBM and such intimate link between risky sexual behaviour and methamphetamine use have led to a possible double epidemic (Halkitis, Green, & Carragher, 2006). In particular, the use of methamphetamine has been found to be correlated to the frequency of unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) among HIV positive and persons with unknown serostatus causal partners over time (Halkitis, Mukherjee, & Palamar, 2009). As an effort to better understand this social pheonemon, this paper focuses on the exploration and identification of the psycho-social and socio-cultural factors of crystal methamphetamine use among the GBM population.

The Psycho-Social and Socio-Cultural Factors of Crystal Methamphetamine Use Among the Gay, Bi and MSM (GBM) Population

In the United States, men who have sex with men (MSM) remain as the demographic group with the highest HIV incidence rates and account for 53% of new HIV infections in 2006 (Rajasingham, Mimiaga, White, Pinkston, Baden, & Mitty, 2012). One of the reasons accounting for such high rates of HIV transmission between gay, bisexual and MSM (GBM) can be attributed to poly-substance use and the use of crystal methamphetamine (Solomon, Halkitis, Moeller, & Pappas, 2012; Rajasingham et al., 2012). The U.S. Centre for Disease Control and Prevention (2007) reported methamphetamine use in the MSM community is of particular concern due to the high prevalence of HIV and the use of the stimulant. Meanwhile, researchers have found methamphetamine use is closely corrleated to sexual risk taking among GBM and such intimate link between risky sexual behaviour and methamphetamine use have led to a possible double epidemic (Halkitis, Green, & Carragher, 2006). In particular, the use of methamphetamine has been found to be correlated to the frequency of unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) among HIV positive and persons with unknown serostatus causal partners over time (Halkitis, Mukherjee, & Palamar, 2009). As an effort to better understand this social pheonemon, this paper focuses on the exploration and identification of the psycho-social and socio-cultural factors of crystal methamphetamine use among the GBM population.