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Background: Population-level estimates of sexual network mixing for parameterizing prediction models of pre-exposure prophylaxis (PrEP) effectiveness are needed to inform prevention of HIV transmission among men who have sex with men (MSM). Estimates obtained by egocentric sampling are vulnerable to information bias due to incomplete respondent knowledge.Methods: We estimated patterns of serosorting and PrEP sorting among MSM in the United States using data from a 2017-2019 egocentric sexual network study. Respondents served as proxies to report the HIV status and PrEP use of recent sexual partners. We contrasted results from a complete-case analysis (unknown HIV and PrEP excluded) versus a bias analysis with respondent-reported data stochastically reclassified to simulate unobserved self-reported data from sexual partners.Results: We found strong evidence of preferential partnering across analytical approaches. The bias analysis showed concordance between sexual partners of HIV diagnosis and PrEP use statuses for MSM with diagnosed HIV (39%; 95% simulation interval: 31, 46), MSM who used PrEP (32%; 21, 37), and MSM who did not use PrEP (83%; 79, 87). The fraction of partners with diagnosed HIV was higher among MSM who used PrEP (11%; 9, 14) compared with MSM who did not use PrEP (4%; 3, 5). Comparatively, across all strata of respondents, the complete-case analysis overestimated the fractions of partners with diagnosed HIV or PrEP use.Conclusions: We found evidence consistent with HIV and PrEP sorting among MSM, which may decrease the population-level effectiveness of PrEP. Bias analyses can improve mixing estimates for parameterization of transmission models. [ABSTRACT FROM AUTHOR]

Background: Long-acting injectable (LAI) human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is reportedly efficacious, although full trial results have not been published. We used a dynamic network model of HIV transmission among men who have sex with men to assess the population impact of LAI-PrEP when available concurrently with daily-oral (DO) PrEP.Methods: The reference model represents the current HIV epidemiology and DO-PrEP coverage (15% among those with behavioral indications for PrEP) among men who have sex with men in the southeastern United States. Primary analyses investigated varied PrEP uptake and proportion selecting LAI-PrEP. Secondary analyses evaluated uncertainty in pharmacokinetic efficacy and LAI-PrEP persistence relative to DO-PrEP.Results: Compared with the reference scenario, if 50% chose LAI-PrEP, 4.3% (95% simulation interval, -7.3% to 14.5%) of infections would be averted over 10 years. The impact of LAI-PrEP is slightly greater than that of the DO-PrEP-only regimen, based on assumptions of higher adherence and partial protection after discontinuation. If the total PrEP initiation rate doubled, 17.1% (95% simulation interval, 6.7%-26.4%) of infections would be averted. The highest population-level impact occurred when LAI-PrEP uptake and persistence improved.Conclusions: If LAI-PrEP replaces DO-PrEP, its availability will modestly improve the population impact. LAI-PrEP will make a more substantial impact if its availability drives higher total PrEP coverage, or if persistence is greater for LAI-PrEP. [ABSTRACT FROM AUTHOR]

The Centers for Disease Control and Prevention estimates that one in four sexually active men who have sex with men (MSM) could decrease their HIV risk by using HIV pre-exposure prophylaxis (PrEP). Because many MSM access healthcare from primary care providers (PCPs), these clinicians could play an important role in providing access to PrEP. Semistructured qualitative interviews were conducted with 31 PCPs in Boston, MA, to explore how they approach decisions about prescribing PrEP to MSM and their experiences with PrEP provision. Purposive sampling included 12 PCPs from an urban community health center specializing in the care of lesbian, gay, bisexual, and transgender persons ('LGBT specialists') and 19 PCPs from a general academic medical center ('generalists'). Analyses utilized an inductive approach to identify emergent themes. Both groups of PCPs approached prescribing decisions about PrEP as a process of informed decision-making with patients. Providers would defer to patients' preferences if they were unsure about the appropriateness of PrEP. LGBT specialists and generalists were at vastly different stages of adopting PrEP into practice. For LGBT specialists, PrEP was a disruptive innovation that rapidly became normative in practice. Generalists had limited experience with PrEP; however, they desired succinct decision-support tools to help them achieve proficiency, because they considered preventive medicine to be central to their professional role. As generalists vastly outnumber LGBT specialists in the United States, interventions to support PrEP provision by generalists could accelerate the scale-up of PrEP for MSM nationally, which could in turn decrease HIV incidence for this priority population. [ABSTRACT FROM AUTHOR]

Introduction: An estimated 1.2 million Americans have indications for using antiretroviral pre‐exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at‐risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. Methods: During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Results and discussion: Thirty‐two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11–33). Most clinicians reported testing and risk‐reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians’ practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. Conclusions: In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale‐up of this efficacious intervention. [ABSTRACT FROM AUTHOR]

Cover Feature: Five-Step Enantioselective Synthesis of Islatravir via Asymmetric Ketone Alkynylation and an Ozonolysis Cascade (Chem. Eur. J. 62/2020) Keywords: asymmetric alkynylation; biocatalysis; ozonolysis; synthesis EN asymmetric alkynylation biocatalysis ozonolysis synthesis 14023 14023 1 11/12/20 20201106 NES 201106 B A ball-and-stick Houk-style view of islatravir b , the target of the total synthesis described in this work, is depicted in the cover image. In the center of the picture is a circle showing the three key catalytic steps of the synthesis; a biocatalytic cascade, an enantioselective alkynylation, and an ozonolysis deprotection cascade. [Extracted from the article]

Introduction: Discontinuations of HIV preexposure prophylaxis (PrEP) by at‐risk individuals could decrease the effectiveness of PrEP. Our objective was to characterize patterns of, reasons for, and clinical outcomes associated with PrEP discontinuations in primary care. Methods: We conducted medical chart reviews for patients prescribed PrEP during 2011 to 2014 at a Boston community health centre specializing in healthcare for sexual and gender minorities. Patients were followed through 2015. We characterized patients' sociodemographics, relationship status, behavioural health conditions, patterns of and reasons for PrEP discontinuations, and HIV seroconversions. Cox proportional hazards models were used to assess patient factors associated with PrEP discontinuations. Results: Of the 663 patients prescribed PrEP, the median age was 33 years, 96% were men who have sex with men (MSM) and 73% were non‐Hispanic white; 40% were in committed relationships and 15% had HIV‐infected partners. Patients either used PrEP continuously (60%), had 1 or more discontinuations (36%), or did not initiate PrEP (4%). Discontinuations were most often due to a decrease in HIV risk perception (33%), non‐adherence to care plans (16%), or insurance barriers (12%). Of the 7 (1.1%) PrEP patients diagnosed with HIV, 1 was HIV‐infected at baseline, 2 seroconverted while using PrEP, and 4 seroconverted after discontinuations. In a multivariable model adjusted for race/ethnicity, relationship status, substance use disorders, and insurance status, those who were less than 30 years old (aHR 2.0, 95% CI 1.4 to 2.9 for ages 18 to 24, aHR 2.2, 95% CI 1.6 to 3.1 for ages 25 to 29, vs. ages 30 to 39 years), who identified as transgender women (aHR 2.0, 95% CI 1.2 to 3.4, vs. cisgender men), and who had mental health disorders (aHR 1.2, 95% CI 1.1 to 1.4 for each additional disorder) were more likely to have discontinuations. Conclusions: Discontinuations of PrEP use among this American sample of predominately MSM were common, particularly among patients who were younger, identified as transgender women, or had behavioural health issues. As HIV seroconversions occurred after discontinuations of PrEP, strategies to prevent inappropriate discontinuations are needed. [ABSTRACT FROM AUTHOR]

Background The reasons why bacterial sexually transmitted infections (BSTIs) are increasing in US men who have sex with men (MSM) have not been fully characterized. Methods An open cohort of MSM accessing medical care at a Boston community health center was used to assess secular trends in BSTI diagnoses. Frequency of infection and the estimated population size were used to calculate diagnosis rates. Poisson models were fit for multivariable analyses. Results Between 2005 and 2015, 19 232 men had at least 1 clinic visit. Most (72.4%) were white; 6.0% were black, and 6.1% were Latino. Almost half had documented self-report of identifying as gay (42.6%) or bisexual (3.2%). Most had private health insurance (61.7%); 5.4% had Medicare, 4.6% had Medicaid, and 8.4% reported no insurance. Between 2005 and 2015, BSTI diagnoses increased more than 8-fold. In 2015, of 1319 men who were diagnosed with at least 1 BSTI; 291 were diagnosed with syphilis, 554 with gonorrhea (51.4% rectal, 31.0% urogenital), and 679 with chlamydia (69.1% rectal, 34.3% urogenital). In 2015, 22.7% of BSTIs were diagnosed among HIV-infected patients (15.4% of the clinic population), and 32.8% of BSTIs were diagnosed among HIV-uninfected patients using pre-exposure prophylaxis (PrEP; 10.1% of all men in care). In multivariable analyses, age 18 to 24 years, being HIV-infected, using PrEP, being nonwhite, or reporting Medicaid or not reporting having private insurance or Medicare were independently associated with being diagnosed with a new BSTI. Conclusions Over the past decade, BSTI diagnosis rates increased in HIV-infected and uninfected MSM, with disproportionate increases in PrEP users, racial and ethnic minority MSM, those aged 25 to 34 years, and those without stable health insurance, warranting focused education, screening, and accessible services for these key subpopulations. [ABSTRACT FROM AUTHOR]

Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes. [ABSTRACT FROM AUTHOR]