Substance abuse and HIV-gp120: are opiates protective?

There has long been a popular conceptual linkage between human immunodeficiency virus (HIV) acquisition and substance abuse involving "needles". Indeed, in vitro studies demonstrate that these substances promote the replication of HIV. Included in these in vitro studies is a linkage or association of tissue damage and viral load with the actions HIV envelope protein gp120 with substances of abuse. However, detailed epidemiological studies have not supported this association of substance abuse and HIV acquisition, viral load and exacerbated tissue damage. It is with this understanding that we undertake a reevaluation of the in vitro studies within the context of the microvascular immune environment. In this regard, a counter-intuitive hypothesis emerges, namely, that specific substances of abuse may afford a degree of protection from HIV infection. This new hypothesis involves the neural, immune, and vascular signaling molecule nitric oxide.