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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA025011-04
Application #
8304396
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Pilotte, Nancy S
Project Start
2008-09-30
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
4
Fiscal Year
2013
Total Cost
$437,511
Indirect Cost
$123,828
Name
University of Missouri Kansas City
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
010989619
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Shah, Ankit; Vaidya, Naveen K; Bhat, Hari K et al. (2016) HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway. Sci Rep 6:18929
Cao, Lu; Walker, Mary P; Vaidya, Naveen K et al. (2016) Cocaine-Mediated Autophagy in Astrocytes Involves Sigma 1 Receptor, PI3K, mTOR, Atg5/7, Beclin-1 and Induces Type II Programed Cell Death. Mol Neurobiol 53:4417-30
Nookala, Anantha R; Li, Junhao; Ande, Anusha et al. (2016) Effect of Methamphetamine on Spectral Binding, Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4. PLoS One 11:e0146529
Gangwani, Mohitkumar R; Kumar, Anil (2015) Multiple Protein Kinases via Activation of Transcription Factors NF-κB, AP-1 and C/EBP-δ Regulate the IL-6/IL-8 Production by HIV-1 Vpr in Astrocytes. PLoS One 10:e0135633
Liu, Xun; Kumar, Anil (2015) Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes. Sci Rep 5:9867
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Nookala, Anantha Ram; Kumar, Anil (2014) Molecular mechanisms involved in HIV-1 Tat-mediated induction of IL-6 and IL-8 in astrocytes. J Neuroinflammation 11:214
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
Silverstein, Peter S; Kumar, Santosh; Kumar, Anil (2014) HIV-1, HCV and alcohol in the CNS: potential interactions and effects on neuroinflammation. Curr HIV Res 12:282-92

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