A correlation between opiate abuse and HIV/AIDS is important to study because opiates are known to cause immunosuppression, and opiate users constitute a major cohort among HIV-positive individuals. We have recently shown that morphine abuse increases virus replication in blood and cerebral compartment of SIV/SHIV-infected Indian rhesus macaques and accelerate onset of clinical disease. Furthermore, we have found that morphine-dependent macaques showed inverse correlation between virus evolution and disease progression. We have also shown that half of the animals, who died within 20 weeks post- infection, did not develop detectable virus-specific immune responses. Therefore our results along with few other recent reports support the phenomenon of opiate-mediated immunosuppression. In view of the fact that opiate abusers represent >25% of total HIV-positive individuals and that opiate abuse causes immunosuppression, it is expected that these individuals would develop weaker immune response when immunized with any vaccine (or candidate vaccine), and thereby vaccine would confer inferior protection against disease. This application is designed to address these issues. We will immunize morphine-dependent and control macaques with a clinically relevant DNA/MVA SHIV AIDS vaccine. These macaques will be monitored for the level and longevity of vaccine-induced cellular and humoral immune responses. The vaccine-mediated protection in these two groups would be monitored by challenge with a chimeric simian human immunodeficiency virus (SHIV89.6P). The results from this study will provide not only proof of concept studies, but also offer a clinically relevant information regarding fate of an AIDS vaccine in a high-risk (opiate-dependent) population. In view of lack of any information in any system makes this study more important because results obtained from this project will also provide an important guideline for other disease systems.

Public Health Relevance

This application proposes to test the efficacy of AIDS vaccine in morphine-dependent macaques. The proposed studies are highly warranted because there is no information available regarding effect of any vaccine in drug-addicted population. Therefore this study will provide guidelines not only in setting of future AIDS vaccine, but also provide guidelines regarding use of any vaccine in such high-risk population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015013-08
Application #
8013549
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Purohit, Vishnudutt
Project Start
2001-09-19
Project End
2011-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
8
Fiscal Year
2011
Total Cost
$646,603
Indirect Cost
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
Rivera, Ivelisse; García, Yashira; Gangwani, Mohitkumar R et al. (2013) Identification and molecular characterization of SIV Vpr R50G mutation associated with long term survival in SIV-infected morphine dependent and control macaques. Virology 446:144-51
Silverstein, Peter S; Shah, Ankit; Weemhoff, James et al. (2012) HIV-1 gp120 and drugs of abuse: interactions in the central nervous system. Curr HIV Res 10:369-83
Chaudhary, Suman; Noel, Richard J; Rodriguez, Nayra et al. (2011) Correlation between CD4 T cell counts and virus compartmentalization in genital and systemic compartments of HIV-infected females. Virology 417:320-6
Silverstein, Peter S; Audus, Kenneth L; Qureshi, Nilofer et al. (2010) Lipopolysaccharide increases the expression of multidrug resistance-associated protein 1 (MRP1) in RAW 264.7 macrophages. J Neuroimmune Pharmacol 5:516-20
Rivera-Amill, Vanessa; Kumar, Rakesh; Noel Jr, Richard J et al. (2010) Short communication: Lack of immune response in rapid progressor morphine-dependent and SIV/SHIV-infected rhesus macaques is correlated with downregulation of TH1 cytokines. AIDS Res Hum Retroviruses 26:919-22
Rivera-Amill, Vanessa; Noel Jr, Richard J; Garcia, Yashira et al. (2010) Accelerated evolution of SIV env within the cerebral compartment in the setting of morphine-dependent rapid disease progression. Virology 398:201-7
Rivera-Amill, Vanessa; Silverstein, Peter S; Noel Jr, Richard J et al. (2010) Morphine and rapid disease progression in nonhuman primate model of AIDS: inverse correlation between disease progression and virus evolution. J Neuroimmune Pharmacol 5:122-32
Rivera-Amill, Vanessa; Noel Jr, Richard J; Román, Ivelisse Rivera et al. (2009) Analysis of the V1V2 region of the SIV envelope in the brains of morphine-dependent and control SIV/SHIV-infected macaques. AIDS Res Hum Retroviruses 25:531-4
Kumar, Anil; Liu, Zhenqian; Sheffer, Darlene et al. (2008) Protection of macaques against AIDS with a live attenuated SHIV vaccine is of finite duration. Virology 371:238-45
Noel Jr, Richard J; Rivera-Amill, Vanessa; Buch, Shilpa et al. (2008) Opiates, immune system, acquired immunodeficiency syndrome, and nonhuman primate model. J Neurovirol 14:279-85

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