Ex Vivo Effect of Methadone Use and Withdrawal on Immune Function and HIV-1 Replication of CD4+ T-Cells from Chronic Methadone Patients Drug abuse remains one of the major risk factors for the spread of HIV-1 infection with opiates being a principal drug of concern. Opiates have been shown to be determining factors in the rate of progression of AIDS. The sum of various in vitro, animal-model, and epidemiological studies Indicates that opiates have conditionally variable effects on HIV-1 disease progression. Immunovirological and pharmacological variability are two major factors that seem to dictate whether HIV-1 infection will progress more rapidly or more slowly in HIV-1 infected opiate-exposed individuals. According to previous studies, the immunovirological effect of an opiate drug such as methadone Is not well characterized in an ex vivo human system. The hypothesis to be tested in this proposal is that ex vivo methadone use and withdrawal will enhance HIV-1 infectivity in CD4+ T-lymphocytes by altering cytokine/chemokine profile and upregulating HIV-1 co-receptor and mu-opioid receptor expression.
The specific aims will analyze various immunovirological determinants of HIV-1 infectivity to evaluate the effects of methadone use and withdrawal. CD4+ T-lymphocytes will be obtained from HIV-1 negative healthy volunteers and chronic (more than one year) methadone patients. Cells will be acutely infected with HIV-1 SF2 (X4/R5 dual virus strain) and then assayed to determine how ex vivo methadone exposure (10-7 and 10-6 M) and abrupt withdrawal: (1) affects HIV-1 infectivity (using HIV-1 p24 ELISA);(2) disrupt cytokine/chemokine profile (using cytometric bead array and ELISA);and (3) modulates the gene and protein expression of extracellular and intracellular molecules (using flow cytometry, quantitative RT-PCR, and Western blot). Statistical analysis will be used to determine significant differences between the different experimental conditions. This study will reveal new cellular and molecular mechanisms involved in methadone-mediated HIV-1 replication enhancement. This data can be used to design future in vivo longitudinal studies on the immune and viral modulating effects of methadone in HIV-1 infected methadone patients

Public Health Relevance

This proposed pilot project will attempt to provide well-controlled laboratory data that may lead to new mechanistic understanding of the effect of opiates such as methadone on Immune function and HIV-1 infectivity and provide the basis to develop more effective treatment interventions for the increasing population of HIV-1 infected methadone users.

National Institute of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)
Research Centers in Minority Institutions Award (G12)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-B)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Universidad Central Del Caribe
United States
Zip Code
Huertas, Adriana; Wessinger, William D; Kucheryavykh, Yuri V et al. (2015) Quinine enhances the behavioral stimulant effect of cocaine in mice. Pharmacol Biochem Behav 129:26-33
Ferchmin, P A; Andino, Myrna; Reyes Salaman, Rebeca et al. (2014) 4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration. Neurotoxicology 44:80-90
Althoff, Keri N; Rebeiro, Peter; Brooks, John T et al. (2014) Disparities in the quality of HIV care when using US Department of Health and Human Services indicators. Clin Infect Dis 58:1185-9
Zayas-Santiago, Astrid; Agte, Silke; Rivera, Yomarie et al. (2014) Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina. PLoS One 9:e97155
Ríos, Grissel; Estrada, Marcos; Mayor, Angel M et al. (2014) Factors associated with tender point count in Puerto Ricans with fibromyalgia syndrome. P R Health Sci J 33:112-6
Rebeiro, Peter F; Horberg, Michael A; Gange, Stephen J et al. (2014) Strong agreement of nationally recommended retention measures from the Institute of Medicine and Department of Health and Human Services. PLoS One 9:e111772
Schikorski, Thomas (2014) Readily releasable vesicles recycle at the active zone of hippocampal synapses. Proc Natl Acad Sci U S A 111:5415-20
Skatchkov, Serguei N; Woodbury-Fariña, Michel A; Eaton, Misty (2014) The role of glia in stress: polyamines and brain disorders. Psychiatr Clin North Am 37:653-78
Santiago-Rodríguez, Eduardo J; Mayor, Angel M; Fernández-Santos, Diana M et al. (2014) Anemia in a cohort of HIV-infected Hispanics: prevalence, associated factors and impact on one-year mortality. BMC Res Notes 7:439
Sanabria-Rios, David J; Rivera-Torres, Yaritza; Maldonado-Dominguez, Gamalier et al. (2014) Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria. Chem Phys Lipids 178:84-91

Showing the most recent 10 out of 18 publications