Optimizing HIV prevention for highly vulnerable methamphetamine-using sexual minority men - SUMMARY This LITE-2 (RFA-AI-21-018) initiative responds to a resurgent epidemic of methamphetamine (meth) use in sexual minority men (SMM), which is a primary driver of HIV incidence. The overarching goals are two-fold: 1) identify multi-level and bio-behavioral determinants of amplified HIV seroconversion risk in meth-using SMM; and 2) test the effectiveness of telehealth motivational enhancement interventions for optimizing entry or re-entry of SMM who use meth into the PrEP care continuum. Findings from our LITE-1 cohort (UG3/UH3 AI-133675, RFA-AI-16-031) and others provide compelling evidence that meth use is increasing, disproportionally impacts racial/ethnic minorities, and accounts for one-in-three new HIV infections in SMM. In response to LITE-2 (RFA- AI-21-018) we propose a multi-component initiative zeroing in on the “Where,” “How,” and “Why” of meth use and HIV risk. Where: What are the geospatial determinants of the association of meth use with HIV incidence? How: How can we support (re-)entry into the PrEP care continuum with this high priority population of SMM who use meth? Why: Does meth amplify biological risk of HIV by potentiating rectal immune dysregulation? Aim 1: Examine multi-level structural, psychological, and social determinants of amplified HIV seroconversion risk in SMM who use meth. The centerpiece of our LITE-2 initiative is a new prospective, bio-behavioral cohort with N=5,000 SMM (n=3,000 SMM who use meth, n=2,000 who do not). Participants will complete assessments over 36 months and provide biological samples for HIV testing, drug toxicology testing, rectal STIs, and rectal cytokines/chemokines. Our primary goal will be to investigate the role of geospatial determinants (e.g., background meth and HIV prevalence, urbanicity) and other structural determinants (e.g., structural stigma of sexual minorities as evidenced by policies/laws) in relation to the association of meth use with amplified HIV seroconversion risk. Aim 2: Test the comparative and combined effectiveness of telehealth motivational enhancement interventions for optimizing PrEP use. PrEP Readiness Interventions for Supporting Motivation (PRISM) is a hybrid type I, modified factorial randomized controlled trial (RCT) of telehealth CM that provides incentives for filling a PrEP prescription, and a 2-session telehealth MI intervention that we adapted with meth- using SMM (R34-DA046367, Carrico/Grov). PRISM will enroll 840 meth-using SMM who are not currently taking PrEP from the LITE-2 cohort (Aim 1) to examine the effectiveness of CM (n = 280), MI (n = 280), and MI+CM (n = 280) on the primary outcome – filling a PrEP prescription. Aim 3: Determine whether greater rectal immune dysregulation partially explains amplified risk of HIV seroconversion in SMM who use meth. Using a case-cohort design, we will compare HIV seroconverters (n=450) with matched seronegative controls (n=450) to examine the clinical relevance of meth-induced alterations in rectal cytokines with respect to HIV seroconversion. This LITE-2 initiative could have an exceptional impact by transforming HIV prevention with SMM.
