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)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Lawrence, Diane M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Missouri Kansas City
Schools of Pharmacy
Kansas City
United States
Zip Code
Nookala, Anantha Ram; Mitra, Joy; Chaudhari, Nitish S et al. (2017) An Overview of Human Immunodeficiency Virus Type 1-Associated Common Neurological Complications: Does Aging Pose a Challenge? J Alzheimers Dis 60:S169-S193
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
Shah, Ankit; Kumar, Anil (2016) Methamphetamine-mediated endoplasmic reticulum (ER) stress induces type-1 programmed cell death in astrocytes via ATF6, IRE1? and PERK pathways. Oncotarget 7:46100-46119
Shah, Ankit; Vaidya, Naveen K; Bhat, Hari K et al. (2016) HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1?, JNK and AP-1 pathway. Sci Rep 6:18929
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
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
Huang, Shengping; Liu, Shufeng; Fu, Jia J et al. (2015) Monocyte Chemotactic Protein-induced Protein 1 and 4 Form a Complex but Act Independently in Regulation of Interleukin-6 mRNA Degradation. J Biol Chem 290:20782-92
Gangwani, Mohitkumar R; Kumar, Anil (2015) Multiple Protein Kinases via Activation of Transcription Factors NF-?B, AP-1 and C/EBP-? Regulate the IL-6/IL-8 Production by HIV-1 Vpr in Astrocytes. PLoS One 10:e0135633
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
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

Showing the most recent 10 out of 28 publications