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Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.

ABSTRACT: We investigated the associations between methamphetamine (meth) use, immune function, and the dynamics of HIV and cytomegalovirus [CMV] in the blood and genital tract of HIV-infected ART-suppressed subjects. Self-reported meth use was associated with increased CD4(+) and CD8(+) T-cell proliferation (Ki67(+), p < 0.005), CD4(+) T-cell activation (CD45RA(-)CD38(+), p = 0.005) and exhaustion (PD-1(+), p = 0.0004) in blood, compared to non-meth users. Meth use was also associated with a trend towards higher blood HIV DNA levels (p = 0.09) and more frequent shedding of CMV in seminal plasma (p = 0.002). To explore possible mechanisms, we compared ex vivo spontaneous and antigen-specific proliferation in PBMC collected from subjects with and without positive meth detection in urine (Utox+ vs. Utox-). Despite higher levels of spontaneous proliferation, lymphocytes from Utox+ meth users had a significantly lower proliferative capacity after stimulation with a number of pathogens (CMV, candida, mycobacterium, toxoplasma, HIV, p < 0.04 in all cases), compared to Utox- participants. Our findings suggest that meth users have greater proliferation and exhaustion of the immune system. Meth use is also associated with a loss of control of CMV replication, which could be related to loss of immune response to pathogens. Future studies should consider meth use as a potential modulator of T-cell responses.

SUBMITTER: Massanella M

PROVIDER: S-EPMC4547398 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.

Massanella Marta M Gianella Sara S Schrier Rachel R Dan Jennifer M JM Pérez-Santiago Josué J Oliveira Michelli F MF Richman Douglas D DD Little Susan J SJ Benson Constance A CA Daar Eric S ES Dube Michael P MP Haubrich Richard H RH Smith Davey M DM Morris Sheldon R SR

Scientific reports 20150824

We investigated the associations between methamphetamine (meth) use, immune function, and the dynamics of HIV and cytomegalovirus [CMV] in the blood and genital tract of HIV-infected ART-suppressed subjects. Self-reported meth use was associated with increased CD4(+) and CD8(+) T-cell proliferation (Ki67(+), p < 0.005), CD4(+) T-cell activation (CD45RA(-)CD38(+), p = 0.005) and exhaustion (PD-1(+), p = 0.0004) in blood, compared to non-meth users. Meth use was also associated with a trend toward ...[more]

PMID: 26299251

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Dataset Information

Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.

Publications

Methamphetamine Use in HIV-infected Individuals Affects T-cell Function and Viral Outcome during Suppressive Antiretroviral Therapy.

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