Club drugs are extensively used by young people with more popularity among gay community (men having sex with men;MSM). It has been established that HIV seroprevalence is higher among methamphetamine users and methamphetamine is known to contribute to HIV-associated dementia (HAD) among HIV-positive individuals. There are also indirect and suggestive indications available that methamphetamine affects the virus replication, prevalence and progression of disease. The prospect of testing proof-of-concept studies regarding the role of methamphetamine in HIV positive humans is untenable because of the variable incubation periods and long time required to address this important issue. Therefore a well-designed study in the macaque model of HIV/AIDS is greatly warranted that will help conclude the effect of methamphetamine abuse on lentivirus pathogenesis, neurological disorder and disease progression in relatively short time. We propose to address these issues in this application. The application proposes to (i) establish the SIV-SHIV/macaque model of chronic methamphetamine exposure and examine whether methamphetamine abuse accelerates the onset of AIDS in macaques, (ii) determine whether chronic methamphetamine exposure affects virus-specific cellular, humoral and mucosal immune responses in SIV- SHIV/macaque model of AIDS, (iii) determine whether METH and SHIV/SIV interaction causes enhanced neuropathological effects on the virus/host interaction in the brain and alterations in dopaminergic systems, and (iv) determine whether virus evolution is different in methamphetamine-exposed macaques compared to that in the control animals.

Public Health Relevance

This application proposes to test the effect of chronic methamphetamine abuse on virus replication, neuropathogenesis and virus-specific immune responses in non-human primate model of HIV/AIDS. The proposed studies are highly warranted because there is no information available regarding effect of methamphetamine abuse.

National Institute of Health (NIH)
Research Project (R01)
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NeuroAIDS and other End-Organ Diseases Study Section (NAED)
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Pilotte, Nancy S
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University of Missouri Kansas City
Schools of Pharmacy
Kansas City
United States
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Jackson, Austin R; Shah, Ankit; Kumar, Anil (2014) Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One 9:e109603
Liu, Xun; Shah, Ankit; Gangwani, Mohitkumar R et al. (2014) HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors. Sci Rep 4:4450
Earla, Ravinder; Kumar, Santosh; Wang, Lei et al. (2014) Enhanced methamphetamine metabolism in rhesus macaque as compared with human: an analysis using a novel method of liquid chromatography with tandem mass spectrometry, kinetic study, and substrate docking. Drug Metab Dispos 42:2097-108
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Kumar, Anil; Silverstein, Peter S (2011) New approaches to the inhibition of replication of viral pathogens. Expert Rev Anti Infect Ther 9:975-7
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