Optimizing HIV prevention for high-risk methamphetamine-using men who have sex with men

Modified Project Summary/Abstract Section This LITE-2 (RFA-AI-21-018) initiative responds to a resurgent epidemic of methamphetamine (meth) use in men who have sex with men (MSM), 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 MSM; and 2) test the effectiveness of telehealth motivational enhancement interventions for optimizing entry or re-entry of MSM 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 and accounts for one-in-three new HIV infections in MSM. 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 MSM 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 MSM who use meth. The centerpiece of our LITE-2 initiative is a new prospective, bio-behavioral cohort with N=5,000 MSM (n=3,000 MSM 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., stigma 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 contingency management (CM) that provides incentives for filling a PrEP prescription, and a 2-session telehealth MI intervention that we adapted with meth-using MSM (R34-DA046367, Carrico/Grov). PRISM will enroll 840 meth-using MSM 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 MSM 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 in the United States.