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Substance use has complex associations to HIV disease progression. The current study tested the associations between several substances and HIV viral load while accounting for confounders relevant to HIV disease progression and substance use. Young sexual minority men and transgender women living with HIV (LWH) in Georgia ( N  = 385) completed measures and biological tests for HIV viral load and substance use. Multivariable regression models tested the role of specific drugs (i.e., alcohol, cannabis/THC, cocaine, and combined amphetamine and methamphetamine) directly on viral load and indirectly through antiretroviral (ART) adherence. ART adherence and HIV care self-efficacy were consistently associated with greater HIV suppression. Alcohol and cocaine were not associated with ART adherence or viral load. Cannabis was negatively associated with ART adherence ( B  = −.053,  p  = .037) but not viral load. Amphetamine/methamphetamine demonstrated significant direct effects on higher viral load ( B  = .708,  p  = .010) while indirectly influencing viral load through a negative association with ART adherence. Our findings support previous research demonstrating amphetamine/methamphetamine use impacts viral load both directly and indirectly through ART adherence. Interventions addressing amphetamine/methamphetamine use by young sexual minority men and transgender women LWH are urgently needed, and future research should focus on determining the mechanisms by which formulations of amphetamine impact HIV replication. Trial registration:ClinicalTrials.gov identifier: NCT03665532 .

Amphetamine use and its associations with antiretroviral adherence and viral load among sexual minority men and transgender women living with HIV