title: 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.
authors: University of California San Diego, La Jolla, CA, United States.
authors: Marta
authors: M
authors: Massanella
authors: University of California San Diego, La Jolla, CA, United States.
authors: Sara
authors: S
authors: Gianella
authors: University of California San Diego, La Jolla, CA, United States.
authors: Rachel
authors: R
authors: Schrier
authors: University of California San Diego, La Jolla, CA, United States.|La Jolla Institute for Allergy &Immunology, La Jolla, CA, United States.
authors: Jennifer M
authors: JM
authors: Dan
authors: University of California San Diego, La Jolla, CA, United States.
authors: Josué
authors: J
authors: Pérez-Santiago
authors: University of California San Diego, La Jolla, CA, United States.
authors: Michelli F
authors: MF
authors: Oliveira
authors: University of California San Diego, La Jolla, CA, United States.|Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
authors: Douglas D
authors: DD
authors: Richman
authors: University of California San Diego, La Jolla, CA, United States.
authors: Susan J
authors: SJ
authors: Little
authors: University of California San Diego, La Jolla, CA, United States.
authors: Constance A
authors: CA
authors: Benson
authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA United States.
authors: Eric S
authors: ES
authors: Daar
authors: University of Southern California Keck School of Medicine, Los Angeles, CA, United States.
authors: Michael P
authors: MP
authors: Dube
authors: University of California San Diego, La Jolla, CA, United States.
authors: Richard H
authors: RH
authors: Haubrich
authors: University of California San Diego, La Jolla, CA, United States.|Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
authors: Davey M
authors: DM
authors: Smith
authors: University of California San Diego, La Jolla, CA, United States.
authors: Sheldon R
authors: SR
authors: Morris
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016022:Case-Control Studies; D049109:Cell Proliferation; D004279:DNA, Viral / Q000032:analysis; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008694:Methamphetamine / Q000627:therapeutic use*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D015488:HIV Antigens; D019713:Receptors, CCR5; D008694:Methamphetamine