HIV Immunocapture Reveals Particles Expressed in Semen under INSTI-based Therapy are Largely Myeloid Cell-Derived and Disparate from Circulating Provirus.

As use of HIV integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13/24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources. Genetic distances were greatest (>2%) between seminal virions and circulating proviruses, pointing to ongoing low-level expression from tissue-resident cells. While the low levels in semen predict an improbable likelihood of transmission, viruses with large genetic distances are expressed under potent INSTI therapy and have implications for determining epidemiologic linkages if adherence is suboptimal.

Safety and Tolerability of Once Daily Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide for Postexposure Prophylaxis After Sexual Exposure.

BACKGROUND: Antiretroviral post-exposure prophylaxis (PEP) is recommended to prevent HIV infection after a high-risk exposure, but current regimens have presented challenges in tolerability, regimen completion, and potential drug-drug interactions. Because coformulated bictegravir, emtricitabine, and tenofovir alafenamide [BIC/FTC/tenofovir alafenamide (TAF)] is effective for HIV treatment, it was evaluated for use for PEP. SETTING: Boston community health center. METHODS: Individuals accessing PEP were enrolled in an open-label study of coformulated BIC/FTC/TAF, taken as one pill daily for 28 days. Pearson's χ2 and Fisher's exact tests were used to assess whether BIC/FTC/TAF differed with respect to side effects and regimen completion rates compared with historical PEP regimens. RESULTS: Between August, 2018 and March, 2020, 52 individuals enrolled in the study. Most identified as cisgender gay (67.3%) or bisexual (11.5%) men, but 7.7% identified as cisgender heterosexual men and 3.8% cisgender heterosexual women. The most common regimen side effects were nausea or vomiting (15.4%), fatigue (9.6%), and diarrhea/loose stools (7.7%), which were less common than historical controls using other PEP regimens, including those containing other integrase strand transfer inhibitors. Only 1 participant discontinued the regimen because of fatigue, and all other side effects were self-limited. Almost all participants (90.4%) completed the indicated regimen, which was a higher completion rate compared with earlier PEP regimens, and none became HIV-positive. CONCLUSIONS: BIC/FTC/TAF coformulated as a single daily pill was found to be safe, well-tolerated, and highly acceptable when used for PEP, and compared more favorably than historical PEP regimens used at an urban health center.

Understanding the HIV Epidemic Among MSM in Baltimore: A Modeling Study Estimating the Impact of Past HIV Interventions and Who Acquired and Contributed to Infections.

INTRODUCTION: Men who have sex with men (MSM) in the United States are disproportionately affected by HIV. We estimated the impact of past interventions and contribution of different population groups to incident MSM HIV infections. SETTING: Baltimore, US. METHODS: We used a deterministic model, parameterized and calibrated to demographic and epidemic Baltimore MSM data, to estimate the fraction of HIV infections among MSM averted by condoms and antiretroviral therapy (ART) over 1984-2017 and the fraction of infections acquired and transmission contributed by MSM from different demographic groups and disease and care continuum stages over 10-year periods from 1988 to 2017, using population attributable fractions. RESULTS: Condom use and ART averted 19% (95% uncertainty interval: 14%-25%) and 23% (15%-31%) of HIV infections that would have occurred since 1984 and 1996, respectively. Over 2008-2017, 46% (41%-52%) of incident infections were acquired by and 35% (27%-49%) of transmissions contributed by MSM aged 18-24 years (who constitute 27% of all MSM, 19% of HIV+ MSM). MSM with undiagnosed HIV infection, those with diagnosed infection but not in care, and those on ART contributed to 41% (31%-54%), 46% (25%-56%), and 14% (7%-28%) of transmissions, respectively. CONCLUSION: Condoms and ART have modestly impacted the HIV epidemic among Baltimore MSM to date. Interventions reaching MSM with diagnosed infection who are not in care should be implemented because the largest percentage of HIV transmissions among Baltimore MSM is attributed to this group.

Improvements in the HIV care continuum needed to meaningfully reduce HIV incidence among men who have sex with men in Baltimore, US: a modelling study for HPTN 078.

INTRODUCTION: HIV prevalence is high among men who have sex with men (MSM) in Baltimore, Maryland, United States, and the levels of viral suppression among HIV-positive MSM are relatively low. The HIV Prevention Trials Network 078 trial seeks to increase the levels of viral suppression among US MSM by increasing the rates of diagnosis and linkage to care and treatment. We estimated the increases in viral suppression needed to reach different HIV incidence reduction targets, and the impact of meeting diagnosis and treatment targets. METHODS: We used a mathematical model of HIV transmission among MSM from Baltimore, US, parameterised with behavioural data and fitted to HIV prevalence and care continuum data for Baltimore wherever possible, to project increases in viral suppression needed to reduce the HIV incidence rate among Baltimore MSM by 10, 20, 30 or 50% after 2, 5 and 10 years. We also projected HIV incidence reductions achieved if US national targets - 90% of people living with HIV (PLHIV) know their HIV serostatus, 90% of those diagnosed are retained in HIV medical care and 80% of those diagnosed are virally suppressed - or UNAIDS 90-90-90 targets (90% of PLHIV know their status, 90% of those diagnosed receive antiretroviral therapy (ART), 90% of those receiving ART are virally suppressed) are each met by 2020. RESULTS: To reduce the HIV incidence rate by 20% and 50% after five years (compared with the base-case at the same time point), the proportion of all HIV-positive MSM who are virally suppressed must increase above 2015 levels by a median 13 percentage points (95% uncertainty interval 9 to 16 percentage points) from median 49% to 60%, and 27 percentage points (22 to 35) from 49% to 75% respectively. Meeting all three US or 90-90-90 UNAIDS targets results in a 48% (31% to 63%) and 51% (38% to 65%) HIV incidence rate reduction in 2020 respectively. CONCLUSIONS: Substantial improvements in levels of viral suppression will be needed to achieve significant incidence reductions among MSM in Baltimore, and to meet 2020 US and UNAIDS targets. Future modelling studies should additionally consider the impact of pre-exposure prophylaxis for MSM.

Test performance and acceptability of self- versus provider-collected swabs for high-risk HPV DNA testing in female-to-male trans masculine patients.

BACKGROUND: High-risk human papillomavirus (hrHPV) causes virtually all cervical cancers. Trans masculine (TM) people (those assigned female at birth who identify with a gender other than female) have low uptake of conventional cervical cancer screening. Self-collected hrHPV DNA testing has high levels of acceptability among cisgender (non-transgender) females and may support increased cervical cancer screening uptake in TM individuals. OBJECTIVE: To assess the test performance and acceptability of self-collected vaginal specimens in comparison to provider-collected cervical swabs for hrHPV DNA detection in TM individuals ages 21-64 years. METHODS: Between March 2015-September 2016, 150 TM participants with a cervix (mean age = 27.5 years; SD = 5.7) completed a one-time study visit comprised of a self-report survey, self-collected vaginal HPV DNA swab, clinician-administered cervical HPV swab, and brief interview on acceptability of clinical procedures. Participants were randomized to complete either self- or provider-collection first to minimize ordering effects. Self- and provider-collected samples were tested for 13 hrHPV DNA types using a DNA Hybridization Assay. The primary outcome variable was the concordance (kappa statistic) and performance (sensitivity, specificity) of self-collected vaginal HPV DNA specimens versus provider-collected cervical HPV swabs as the gold standard. RESULTS: Of the 131 participants completing both the self- and provider-collected HPV tests, 21 cases of hrHPV were detected by the provider cervical swab (gold standard; 16.0% hrHPV prevalence); 15 of these cases were accurately detected by the self-collected vaginal swab (71.4% concordance) (Kappa = 0.75, 95% Confidence Interval [CI]: 0.59, 0.92; p<0.001). Compared to the provider-collected cervical hrHPV DNA sample (gold standard), the self-collected vaginal hrHPV DNA test demonstrated a sensitivity of 71.4% (95% CI: 0.52, 0.91; p = 0.0495) and specificity of 98.2% (95% CI: 0.96, 1.00; p<0.0001). Over 90% of participants endorsed a preference for the self-collected vaginal swab over provider-collected cervical swab. CONCLUSION: Self-collected vaginal swabs are highly acceptable to TM as a means to test for hrHPV DNA. Test performance of this self-collection method for hrHPV detection in TM is consistent with previous studies in cisgender females. Self-collected vaginal swab testing for hrHPV DNA represents a reasonable and patient-centered strategy for primary cervical cancer screening in TM patients unwilling to undergo provider collection of specimens via speculum exam.

Optimal HIV Postexposure Prophylaxis Regimen Completion With Single Tablet Daily Elvitegravir/Cobicistat/Tenofovir Disoproxil Fumarate/Emtricitabine Compared With More Frequent Dosing Regimens.

STRUCTURE: The study evaluated elvitegravir/cobicistat/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis (PEP). BACKGROUND: HIV-exposed individuals may benefit from PEP, but completion rates have been suboptimal because of regimen complexity and side effects. Newer antiretroviral combinations coformulated as single daily pills may optimize PEP adherence. SETTING: One hundred HIV-uninfected individuals who presented to a Boston community health center after an acute HIV sexual exposure were enrolled and initiated PEP with the daily, single-pill combination Quad pill for a 28-day course. METHODS: Side effects and medication completion rates from study participants were compared with historical controls who had used PEP regimens consisting of TDF/FTC daily and raltegravir twice daily, or earlier regimens of twice daily zidovudine (AZT)/lamivudine (3TC) and a protease inhibitor, using χ tests for independence. RESULTS: Of the 100 participants who initiated the Quad pill for PEP after a high-risk sexual exposure, 71% completed the 28-day Quad pill regimen, which was significantly greater than historical controls who used TDF/FTC and raltegravir (57%, P < 0.05) or AZT/3TC plus a protease inhibitor (39%, P < 0.001). The most common side effects reported by Quad pill users were as follows: abdominal discomfort or pain, gas or bloating (42%), diarrhea (38%), fatigue (28%), nausea or vomiting (28%), headache (14%), or dizziness or lightheadedness (6%). Most symptoms were mild, limited, and did not result in medication discontinuation. No participants became HIV infected. CONCLUSIONS: Fixed-dose combination of elvitegravir/cobicistat/TDF/FTC was safe and well tolerated for PEP, with higher regimen completion rates than more frequently dosed PEP regimens.

Comparing self- and provider-collected swabbing for HPV DNA testing in female-to-male transgender adult patients: a mixed-methods biobehavioral study protocol.

BACKGROUND: Cervical cancer, nearly all cases of which are caused by one of several high-risk strains of the human papillomavirus (hr-HPV), leads to significant morbidity and mortality in individuals with a cervix. Trans masculine (TM) individuals were born with female reproductive organs and identify as male, man, transgender man, or another diverse gender identity different from their female assigned sex at birth. Routine preventive sexual health screening of TM patients is recommended, including screening for cervical cancer and other sexually transmitted infections (STIs); however, as many as one in three TM patients are not up-to-date per recommended U.S. GUIDELINES: Among cisgender (non-transgender) women, self-swab hr.-HPV DNA testing as a primary cervical cancer screening method and self-swab specimen collection for other STIs have high levels of acceptability. No study has yet been conducted to compare the performance and acceptability of self- and provider-collected swabs for hr.-HPV DNA testing and other STIs in TM patients. METHODS: This article describes the study protocol for a mixed-methods biobehavioral investigation enrolling 150 sexually active TM to (1) assess the clinical performance and acceptability of a vaginal self-swab for hr.-HPV DNA testing compared to provider cervical swab and cervical cytology, and (2) gather acceptability data on self-collected specimens for other STIs. Study participation entails a one-time clinical visit at Fenway Health in Boston, MA comprised of informed consent, quantitative assessment, venipuncture for syphilis testing and HIV (Rapid OraQuick) testing, randomization, collection of biological specimens/biomarkers, participant and provider satisfaction survey, and qualitative exit interview. Participants are compensated $100. The primary study outcomes are concordance (kappa statistic) and performance (sensitivity and specificity) of self-collected vaginal HPV DNA specimens vs provider-collected cervical HPV swabs as a gold standard. DISCUSSION: This study addresses critical gaps in current clinical knowledge of sexual health in TM patients, including comparing alternative strategies for screening and diagnosis of cervical cancer, hr.-HPV, and other STIs. Findings have implications for improving the delivery of sexual health screening to this often overlooked and underserved patient population. Less-invasive patient-centered strategies may also generalize to other at-risk cisgender female populations that face barriers to timely and needed STI and cervical cancer screening. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02401867.

Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence.

Antiretroviral drugs have been recommended for postexposure prophylaxis (PEP) after high-risk sexual exposures for more than a decade. Three drug regimens could offer the highest levels of protection, particularly if the infectious source is taking medication, but drug intolerance has often led to suboptimal adherence. The current study evaluated a novel 3-drug PEP regimen, consisting of raltegravir, tenofovir DF, and emtricitabine. Of 100 participants enrolled in this study at a Boston community health center that has had a comprehensive PEP program for more than a decade, 85 were evaluable at 3 months and none became HIV infected. Fifty seven percent of those enrolled completed the regimen as prescribed, and 27% took their medicine daily, but sometimes missed the second daily dose of Raltegravir. The most common side effects reported included nausea or vomiting (27%), diarrhea (21%), headache (15%), fatigue (14%), abdominal symptoms (including pain, gas, or bloating) (16%), and myalgias or arthralgias (8%), all of which were mild and tended to be self-limited, not resulting in drug discontinuation. The side effects were significantly less common than those reported by historical controls, who used a 3-drug PEP regimen including zidovudine, lamivudine, and a ritonavir-boosted protease inhibitor. Raltegravir, tenofovir DF, and emtricitabine may be useful as a 3-drug regimen for PEP.