Introduction Trans masculine people who have sex with cisgender (“cis”) men (“trans MSM”) may be at‐risk for HIV infection when they have cis MSM partners or share needles for hormone or recreational drug injection. Limited data are available characterizing indications and uptake of pre‐exposure prophylaxis (PrEP) in trans MSM. The aim of this study was to assess PrEP indication and uptake as a means of primary HIV prevention for adult trans MSM in the U.S. Methods Between November and December 2017, a national convenience sample of trans MSM in the U.S. (n = 857) was recruited using participatory methodologies and completed an online survey of demographics, HIV risk, PrEP, behavioural and psychosocial factors. Self‐reported receptive anal sex or frontal/vaginal sex (with or without a condom) with a cis male sex partner in past six months was an eligibility criterion. A multivariable logistic regression procedure was used to model PrEP indications (yes/no) per an interpretation of U.S. Centers of Disease Control and Prevention recommendations among those without HIV (n = 843). Results The diverse sample was 4.9% Black; 22.1% Latinx ethnicity; 28.4% non‐binary gender identity; 32.6% gay‐identified; 82.7% on testosterone. Overall, 84.1% had heard of PrEP. Of these, 33.3% reported lifetime PrEP use (21.8% current and 11.5% past). Based on HIV behavioural risk profiles in the last six months, 55.2% of respondents had indications for PrEP. In a multivariable model, factors associated with PrEP indication included where met sex partners, not having sex exclusively with cismen, higher perceived HIV risk, greater number of partners and high cis male partner stigma (all p < 0.05). Discussion The majority of trans MSM in this sample had a PrEP indication. Stigma was associated with risk for HIV acquisition and represents a critical target for HIV biobehavioural prevention interventions for trans MSM, who appear to be underutilizing PrEP. Conclusions Results from this study support the full inclusion of trans MSM in HIV biobehavioural prevention efforts. Public health interventions and programmes are needed to reach trans MSM that attend to general MSM risk factors as well as to vulnerabilities specific to trans MSM, including the context of stigma from cis male sexual partners.

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