Modeling the Effects of Morphine-Altered Virus Specific Antibody Responses on HIV/SIV Dynamics

Mutua, Jones M.; Perelson, Alan S.; Kumar, Anil; Vaidya, Naveen K.

doi:10.1038/s41598-019-41751-8

Modeling the Effects of Morphine-Altered Virus Specific Antibody Responses on HIV/SIV Dynamics

Journal Article · Mon Apr 01 00:00:00 EDT 2019 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-019-41751-8· OSTI ID:1619505

Mutua, Jones M.; ; ; Vaidya, Naveen K.

Abstract

Drugs of abuse, such as opiates, have been widely associated with enhancing HIV replication, accelerating disease progression and diminishing host-immune responses, thereby making it harder to effectively manage HIV infection. It is thus important to study the effects of drugs of abuse on HIV-infection and immune responses. Here, we develop mathematical models that incorporate the effects of morphine-altered antibody responses on HIV/SIV dynamics. Based on fitting the model to experimental data from simian immunodeficiency virus (SIV) infections in control and morphine-addicted macaques, we found that two of the most significant effects of virus specific antibodies are neutralizing viral particles and enhancing viral clearance. Using our model, we quantified how morphine alters virus-specific antibody responses, and how this alteration affects the key components of virus dynamics such as infection rate, virus clearance, viral load, CD4 ⁺ T cell count, and CD4 ⁺ T cell loss in SIV-infected macaques under conditioning with morphine. We found that in a subpopulation of SIV-infected morphine addicted macaques, the presence of drugs of abuse may cause significantly diminished antibody responses, resulting in more severe infection with increased SIV infectivity, a decreased viral clearance rate, increased viral load, and higher CD4 ⁺ T cell loss.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 1619505

Alternate ID(s):: OSTI ID: 1526947

Report Number(s):: LA-UR--17-31293; 5423; PII: 41751

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 9; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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