Opiates as potential cofactors in progression of HIV-1 infections to AIDS

Abstract

Because of the widely documented association of AIDS with opiate abuse, there is considerable interest in knowing whether opiates alter progression of HIV-1 infections to AIDS. The main reason for this interest is that opiates and opiate-abuse have been shown to have broad influence on immune processes as well as in vitro expressions of HIV-1. This article reviews literature defining the connection between opiate use and AIDS. Basic understanding of the effects of opiates on immune process and HIV-1 infection, especially as derived from study of a monkey model of AIDS, are discussed as well as epidemiological data regarding the connection between chronic injected drug abuse and AIDS, in the context of current knowledge about the HIV-1 infectious process and AIDS pathogenesis. Theoretically, there is ample reason to suspect that opiates are involved in progression of HIV-1 infections to AIDS. To date, however, epidemiological approaches have been unable to link decline in CD4 T-cell counts, as a marker of AIDS progression, with opiate use—although other indices of AIDS progression have yet to be thoroughly evaluated in this regard. Also, the impact of opiate use and abuse on opportunistic infections occurring prior to or concurrent with HIV-1 infection has not been closely scrutinized. Interestingly, despite considerable evidence delineating the potential of opiates to exacerbate HIV-1 infections, there is suggestive evidence from both clinical observations and basic studies that homeostatically balancing conditions of chronic, consistent opiate exposure have the potential to protect the host from progression of HIV-1 infections—a situation that may well differ from when opiate-naive subjects first experience exposure to opiates and when opiate dependency is not maintained in a consistent fashion. Taken together, therefore, information from basic studies, including most particularly studies with monkeys, and epidemiological studies, indicates that effects of opiates on progression to AIDS may be conditionally variable. There are many aspects of the drug abuse culture that have potentially offsetting consequences in terms of their potential to up- or down-regulate both HIV-1 expression and host protective responses thereto that could be relevant in this regard. In conclusion, many ambiguities are yet to be considered, and basic and epidemiological studies to be pursued before the opiate-AIDS connection is fully understood.