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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

Marta Massanella, Sara Gianella, Rachel Schrier, Jennifer M. Dan, Josué Pérez-Santiago, Michelli F. Oliveira, Douglas D. Richman, Susan J. Little, Constance A. Benson, Eric S. Daar, Michael P. Dube, Richard H. Haubrich, Davey M. Smith, Sheldon R. Morris

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. More... »

PAGES

13179

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep13179

DOI

http://dx.doi.org/10.1038/srep13179

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029039591

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26299251


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