In vivo effects of methamphetamine on HIV-1 replication: A population-based study

Drug Alcohol Depend. 2016 Feb 1:159:246-54. doi: 10.1016/j.drugalcdep.2015.12.027. Epub 2016 Jan 4.

Abstract

Background: Although a number of in vitro studies have shown that methamphetamine (METH) can increase HIV-1 replication in human immune cells, a direct link between METH use and HIV-1 pathogenesis remains to be determined among HIV-1 patients.

Methods: According to the status of METH use and HIV-1 infection, we enrolled participants and divided them into four groups: METH+HIV+, METH-HIV+, METH+HIV-, and METH-HIV-. HIV viral loads and HIV-1-related cellular factors were measured and compared among different groups.

Results: A total of 60 participants were enrolled into this study, 15 within each group. HIV viral loads in METH+HIV+ group were significantly higher than those in METH-HIV+ group, while CD4+ T cell counts had an inverse trend between the two groups (p<0.05). METH users or HIV-1 infected patients had lower CCR5+, CXCR4+ percentages in CD4+ T cells than METH-HIV- subjects (p<0.01). However, METH use had little effect on CD3 expression in PBMCs and the levels of MIP-1α, MIP-1β and IL-6 in PBMCs or plasma, which were increased by HIV-1 infection with or without METH. TLR-9 and IFN-α levels in PBMCs of METH users with or without HIV infection were higher than non-METH users (p<0.05).

Conclusions: METH use is associated with higher viral loads and lower CD4+ T cell counts in HIV-infected individuals. This finding may be mediated by activation of innate immunity (TLR-9, IFN-α) by METH use.

Keywords: HIV-1 entry; HIV-1 pathogenesis; Methamphetamine (METH) use; TLR-9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Chemokine CCL3 / blood
  • Chemokine CCL3 / metabolism
  • Chemokine CCL4 / blood
  • Chemokine CCL4 / metabolism
  • Down-Regulation
  • Female
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / growth & development*
  • Humans
  • Immunity, Innate / drug effects
  • Interferon-alpha / biosynthesis
  • Interleukin-6 / blood
  • Interleukin-6 / metabolism
  • Male
  • Methamphetamine / pharmacology*
  • Methamphetamine / urine
  • Middle Aged
  • Receptors, CCR5 / biosynthesis
  • Receptors, CXCR4 / biosynthesis
  • Toll-Like Receptor 9 / biosynthesis
  • Viral Load / drug effects*

Substances

  • CCR5 protein, human
  • CXCR4 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Interferon-alpha
  • Interleukin-6
  • Receptors, CCR5
  • Receptors, CXCR4
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Methamphetamine