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Methamphetamine Use Tied to T-Cell Activation and Proliferation in Men on ART
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CROI 2014, March 3-6, 2014, Boston
Mark Mascolini
US men who have sex with men (MSM) who used methamphetamine had greater T-cell activation and proliferation than nonusers, even though they had an undetectable viral load [1]. This San Diego study of 50 men also produced evidence that meth users may have a deeper HIV DNA reservoir than nonusers.
Compared with HIV-positive people who do not use meth, those who do have a higher risk of cognitive impairment and faster progression to AIDS [2,3], noted researchers from the University of California, San Diego (UCSD). But the reasons for these associations remain unclear. Worse antiretroviral adherence or meth-related risk behaviors could explain worse health outcomes in meth users, or some physiologic mechanism could explain these health deficits.
To address these questions, UCSD researchers evaluated use of methamphetamine and other recreational drugs in 50 MSM with a viral load below 50 copies on long-term antiretroviral therapy. Once a month these men completed internet-based questionnaires about antiretroviral adherence and party drug use as part of a 1-year trial to reduce sexually transmitted infection incidence. The researchers defined meth use as reporting use in at least one survey over the study period. They used frozen peripheral blood mononuclear cells (PBMCs) to assess standard markers of immune cell activation and proliferation and to measure total HIV DNA and cellular HIV RNA.
The 50 men averaged 46 years in age and had taken antiretrovirals for an average 4 years. The highest proportion of men (42%) were white, 20% were black, and 4% Hispanic. CD4 counts averaged 637, and all men had a viral load below 50 copies. Sixteen men reported using meth, 20 marijuana, 13 other club drugs, 12 alcohol, and 11 cocaine.
Men who used meth did not differ from nonusers in age, time on ART, CD4 count, CD8 count, or sexually transmitted infections. Meth users had significantly higher cytomegalovirus (CMV) shedding in semen (P = 0.0019), a trend toward more HIV shedding in semen (P = 0.09), and a trend toward a lower (worse) CD4/CD8 ratio (0.75 versus 0.97, P = 0.09). Meth users and nonusers did not differ in self-reported adherence to antiretrovirals.
Compared with men who did not use meth, those who did had significantly higher levels of activated (CD45RA-CD38+) CD4 cells (P = 0.049) and proliferating (Ki67+) CD4 cells (P < 0.05) and CD8 cells (P < 0.01). The link between meth and higher Ki67 in total CD4 and CD8 cells remained significant after statistical adjustment for CMV shedding or CMV load in seminal plasma. Increased proliferation of all T-cell subsets analyzed (naive, central memory, transitional memory, effector memory CD8s) suggested to the investigators "a general and unspecific effect of meth in these cells in vivo."
The proviral HIV DNA reservoir tended to be higher in meth users than nonusers (median 2.09 versus 1.83 log10 copies/million CD4 cells, P = 0.09). And levels of 2-LTR circles, indicating the amount of viral DNA imported into cell nuclei, was nonsignificantly higher in meth users (P = 0.08).
Use of other recreational drugs did not have a significant impact on levels of immunologic or virologic markers.
The impact of meth use on T-cell activation and proliferation, the researchers proposed, "could explain meth-related co-morbidities" in HIV-positive people who use meth. The trend toward a deeper proviral DNA reservoir and more HIV RNA in seminal plasma among meth users, the UCSD team speculated, "could explain increased HIV transmission and worse HIV disease progression" in meth users.
References
1. Massanella M, Gianella S, Richman D, et al. Impact of methamphetamine use on immunologic and virologic markers during suppressive ART. CROI 2014. Conference on Retroviruses and Opportunistic Infections. March 3-6, 2014. Boston. Abstract 306.
2. Carey CL, Woods SP, Rippeth JD, Gonzalez R, Heaton RK, Grant I. Additive deleterious effects of methamphetamine dependence and immunosuppression on neuropsychological functioning in HIV infection. AIDS Behav. 2006;10:185-190.
3. Cherner M, Letendre S, Heaton RK, et al. Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology. 2005;64:1343-1347.
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