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

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

doi:10.1038/srep13179

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.

Highlights

In HIV-infected individuals, meth use is associated with delayed viral suppression after the initiation of antiretroviral therapy (ART), higher levels of blood HIV RNA, increased frequency of drug resistance mutations, and accelerated progression to AIDS10–14
Only 4 participants had HIV shedding in the genital tract in this cohort, there was a trend towards a higher frequency of genital HIV shedding in meth users (p = 0.09, Table 1)
Since meth use is linked to reduced adherence to ART and a failure to suppress HIV replication, it has been difficult to differentiate between direct effects of meth and those resulting from residual HIV replication related to non-adherence[12]

Summary

Introduction

In HIV-infected individuals, meth use is associated with delayed viral suppression after the initiation of antiretroviral therapy (ART), higher levels of blood HIV RNA, increased frequency of drug resistance mutations, and accelerated progression to AIDS10–14. There were no differences in CD8+ T-cell immune activation between groups, as measured by the frequency of CD45RA–CD38+ or HLA-DR+CD38+ (Fig. 1A), but there was a trend towards higher levels of CD45RA–HLA-DR+ in the non meth users compared to the users (p = 0.08, Fig. 1A).

Results

Conclusion