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Chapter 29 : Substance Use Disorders and Neuro-AIDS in the HAART Era
Category: Viruses and Viral Pathogenesis
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This chapter reviews the studies which provide evidence for a synergistic effect of drugs of abuse and human immunodeficiency virus (HIV) infection on brain function. Understanding the interactive mechanisms of this neurodegeneration is critical to our ability to optimize therapy for drug-abusing HIV-infected populations. The chapter discusses the proposed underlying mechanisms of this combined neurotoxicity, the current state of knowledge about the role of highly active antiretroviral therapy (HAART) in this interaction, and implications for future research and therapeutic development. It discusses the evidence that each of the drugs of abuse interacts with HIV infection through influences on the dopaminergic system and by other mechanisms as well. A recent study showed that morphine inhibits CD8-positive T-cell-mediated noncytotoxic anti-HIV activity in latently infected human immune cells, largely by interfering with a gamma interferon signaling pathway. Naltrexone blocked this morphine-induced inhibition. This study suggests that morphine impairs the anti-HIV function of the immune system. In injection drug users, HAART utilization decreases mortality compared to nonutilization, though all injection drug users, with or without HAART utilization, have better survival in the HAART era than in the pre-HAART era. By stopping the interactive mechanisms discussed in this chapter, it would seem reasonable that drug abstinence would halt or potentially reverse the synergistic progression of HIV-associated dementia in drug-abusing individuals. Further work is needed to optimize and develop new strategies for the benefit of the drug-abusing population.
MRI scan of a patient with HIV infection who abused heroin and cocaine. This 51-year-old HIV-infected woman used cocaine several days per week and heroin on a regular basis. She was admitted to Johns Hopkins Hospital with the subacute onset of ataxia, postural instability, and severe dementia. Her CD4 cell count was 5 cells/mm3, and her plasma viral load was 436,000 copies/ml. MRI scan shows bilateral hyperintensities in the basal ganglia, without edema.
Synergistic neurotoxicity with HIV proteins and drugs of abuse. Human fetal neurons were incubated with HIV proteins gp120 (g) (30 pM) and Tat (T) (40 nM) at subneurotoxic dosages with or without methamphetamine (meth) (500 µM) or cocaine (16 µM). Changes in mitochondrial membrane potential were measured using JC-1 fluorescent dye. Synergistic neurotoxicity was noted as shown (modified from Turchan et al., 2001 ). Data are presented as mean + standard error of the mean and calculated as percentage of control. Untreated cells were used as control.