Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep13179
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Funding
- Department of Veterans Affairs
- James Pendleton Charitable Trust
- amfAR grant [108537]
- FAIR
- US National Institutes of Health (NIH) [AI69432, AI106039, MH62512, MH083552, AI100665, AI077304, AI047745, AI74621, GM093939AI080353, AI096113, AI306214, AI27670, AI064086, K24, AI43638, MH100979]
- California HIV/AIDS Research Program [RN07-SD-702, MC08-SD-700, EI-11-SD-005]
- National Center for Advancing Translational Sciences through UCLA CTSI Grant [UL1TR000124]
- National Institute of General Medical Sciences grant [GM093939]
- TMARC developmental grant [P50DA026306, R25MH081482]
- EMBO
- CNPq-Brazil post-doctoral fellowships
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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.
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