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

• Published in: Scientific reports Vol. 5; no. 1; p. 13179
• Main Authors: Massanella, Marta, Gianella, Sara, Schrier, Rachel, Dan, Jennifer M., Pérez-Santiago, Josué, Oliveira, Michelli F., Richman, Douglas D., Little, Susan J., Benson, Constance A., Daar, Eric S., Dube, Michael P., Haubrich, Richard H., Smith, Davey M., Morris, Sheldon R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2015; Nature Publishing Group
• Subjects: 692/420/2780; 692/499; Adult; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; Blood; Case-Control Studies; Cell Proliferation; Cytomegalovirus; DNA, Viral - analysis; HIV Antigens - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunology; Infections; Lymphocytes; Lymphocytes T; Methamphetamine; Methamphetamine - therapeutic use; Middle Aged; Monocytes - immunology; multidisciplinary; Pathogens; Receptors, CCR5 - metabolism; Science; T cell receptors; T-Lymphocytes - immunology; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13179

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.