Modeling HIV-1 Infection and Immune Responses Under Drugs of Abuse
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The frequent use of drugs of abuse among HIV infected individuals is a major concern. Drugs of abuse, such as opiates, have been widely associated with enhanc ing HIV replication, accelerating disease progression, and diminishing host-immune responses. Moreover, opiates such as morphine have also been associated with de creasing the viral mutation rate. The rapid replication of HIV may result in increased production of mutant viruses that can escape detection by the host’s immune system. This shows that the use of drugs of abuse can make it harder to eﬀectively manage HIV infections. It is thus important to gain insights into the eﬀects of drugs of abuse on HIV dynamics. This dissertation presents mathematical models that help inves tigate the eﬀects of morphine-altered antibody responses on SIV dynamics, eﬀects of morphine pharmacodynamics on HIV dynamics, and eﬀects of morphine on HIV infections with two viral species. Using our models, we show 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. We also show that the infection threshold, the viral load, and the CD4+ T cell count largely depend on morphine pharmacodynamic parameters. Magnitudes of the basic reproduction number, and the numerical simu lations results of our two viral species model show that the wild type virus dominates both in the presence of morphine and in the absence of morphine. The presence of morphine generally results in higher proportion of wild-type virus than mutant virus thereby resulting into a higher total viral load. Results in this dissertation may be useful to develop HIV control strategies, such as antibody based vaccines, for drug abuse groups.
Table of Contents
Introduction -- HIV background and literature review -- Modeling HIV dynamics in morphine-altered antibody responses -- Effects of morphine pharmacodynamics on HIV-infection dynamics -- Effect of morphine on HIV-infection with two viral species -- Conclusions and discussion