HIV-1 neuropathogenesis and abused drugs: Current views, problems, and solutions

HIV Associated Dementia (HAD) and peripheral neuropathy result from HIV- 1 infection and several parameters impact on their initiation and course. These parameters include properties of the virus such as sequence heterogeneity of the envelope protein and virus and host gene expression in infected and uninfected macrophages in HIV infected individuals. The infection of brain cells such as macrophage/microglia may influence the course and duration of HAD through the elaboration of toxic molecules and viral host by-products of infection. Drugs of abuse complicate our interpretation of the resulting pathologies and affect the molecular and biochemical processes involved in HIV-1 infection and its life cycle. Furthermore, abused drugs may modulate the biology and function of macrophage/microglia as well as other cells in brain. Total HIV-1 virus load in the brain may also impact the clinical consequences of infection. Although specific strains of HIV-1 may inflict HAD by interactions at the molecular level, other mechanisms may operate in the initiation and development of peripheral neuropathy. An important aspect of these studies is the determination of their accuracy, specificity, sensitivity, and reproducibility. We describe important caveats involved in the performance, analysis, and interpretation of the results.