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As the second largest group of persons to have been infected with human immunodeficiency virus (HIV), and the most likely to transmit HIV to heterosexual partners in the United States and Europe, iv drug users will play an increasingly important role in the future of the AIDS epidemic. This paper reviews five emerging critical issues regarding HIV infection among iv drug users. In epidemiology, rates of drug injection and anonymous sharing of injection equipment appear related to rapid spread of HIV among iv drug users, while heterosexual transmission from iv drug users appears to have been occurring at a relatively slow but constant rate. Data exist that support a gender-related cofactor and a continuing drug injection cofactor, but mechanisms for these potential cofactors have not been determined. Besides frank AIDS, HIV infection also appears to lead to epidemic-level increases in a variety of fatal infections among iv drug users. Several studies of prevention show active risk reduction among iv drug users, but new methods are urgently needed to increase amount of risk reduction.

There is strong epidemiologic evidence from studies of i.v. drug users in New York City for the existence of one or more gender-related cofactors in response to HIV infection. The strength of the evidence comes from the variety of data sets that indicate a gender-related cofactor and from the consistency of the pattern found: in all of the data sets, females appear to have a more "favorable" response than do males. The extent of underrepresentation of females in the cases of AIDS in i.v. drug users--a possible 35% reduction in the development of clinical AIDS-suggests that such a cofactor should be considered of practical importance. Identifying the mechanism(s) for a gender difference may lead to ways of deliberately affecting the course of the infection. Further research on the gender difference may also contribute to our understanding of interactions among the various components of the immune system and the interaction of the immune system with other behavioral and physiologic systems.