The specific aims of this study were to 1) to determine the effect of injection drug use on the degree of CD4+ T cell depletion in the GI tract and whether this effect is modified by HIV, 2) explore the effect of IDU on systemic immune activation and investigate its impact on the mucosal immune system in the absence and presence of chronic untreated HIV-1 infection and 3) ascertain the relationship between IDU-related behavioural factors and measures of HIV disease, including the degrees of CD4+ T cell depletion and the levels of HIV-1 RNA. The gene discussed is CD4; the disease is HIV-1 infection.