Jennifer A Fulcher1,2, Steven Shoptaw3, Solomon B Makgoeng4, Julie Elliott5, F Javier Ibarrondo1, Amy Ragsdale4, Ron Brookmeyer6, Peter A Anton5, Pamina M Gorbach1,4. 1. Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 2. Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA. 3. Department of Family Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 4. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA. 5. Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 6. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA.
Abstract
BACKGROUND: Methamphetamine use increases the risk of HIV-1 infection among seronegative users and can exacerbate disease progression in HIV-positive users. The biological mechanisms underlying these associations remain unclear. In this cross-sectional pilot study, we examine the associations between recent methamphetamine use and inflammation in the rectal mucosa and peripheral blood compartments in HIV-1 seropositive and seronegative men who have sex with men. METHODS: HIV-seronegative and HIV-seropositive men who have sex with men participants were enrolled (N = 24). Recent methamphetamine use was determined by urine drug screen. Cytokines were quantified using multiplex arrays from collected plasma and rectal sponge samples, and peripheral blood T-cell activation was assessed by flow cytometry. RESULTS: Methamphetamine use was associated with consistently increased rectal inflammatory cytokines, specifically interleukin-6 and tumor necrosis factor-alpha, regardless of HIV-1 serostatus in this pilot study. This association was significant after adjusting for age, HIV-serostatus, and receptive anal intercourse frequency using regression analysis. Similar increases were not uniformly observed in peripheral blood. CONCLUSIONS: Methamphetamine use is associated with increased local mucosal inflammatory cytokine production. These findings may help explain the increased HIV-1 risk seen in methamphetamine users and contribute to increased inflammation among HIV-seropositive users.
BACKGROUND:Methamphetamine use increases the risk of HIV-1 infection among seronegative users and can exacerbate disease progression in HIV-positive users. The biological mechanisms underlying these associations remain unclear. In this cross-sectional pilot study, we examine the associations between recent methamphetamine use and inflammation in the rectal mucosa and peripheral blood compartments in HIV-1 seropositive and seronegative men who have sex with men. METHODS: HIV-seronegative and HIV-seropositivemen who have sex with menparticipants were enrolled (N = 24). Recent methamphetamine use was determined by urine drug screen. Cytokines were quantified using multiplex arrays from collected plasma and rectal sponge samples, and peripheral blood T-cell activation was assessed by flow cytometry. RESULTS:Methamphetamine use was associated with consistently increased rectal inflammatory cytokines, specifically interleukin-6 and tumor necrosis factor-alpha, regardless of HIV-1 serostatus in this pilot study. This association was significant after adjusting for age, HIV-serostatus, and receptive anal intercourse frequency using regression analysis. Similar increases were not uniformly observed in peripheral blood. CONCLUSIONS:Methamphetamine use is associated with increased local mucosal inflammatory cytokine production. These findings may help explain the increased HIV-1 risk seen in methamphetamine users and contribute to increased inflammation among HIV-seropositive users.
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