Co-use of illicit drugs, in particular cocaine and alcohol, is common among HIV-1(+) men and women of different ethnic groups. We compared cohorts of alcohol and cocaine co-users HIV-1(+) African American women and in cohorts of drug-free, or methamphetamine users HIV-1(+) men. We monitored clinical cellular immune parameters at repeated regular intervals. We found that significant inverse correlations between (CD8+)CD38+ cells and subpopulations of CD4+ cells distinguished by the expression of CD45RA in HIV-1(+) alcohol and cocaine co- users but not in drug-free HIV-1(+) patients. Following stratification for CD4+ cell number, we found the (CD4+)CD45RA+ subpopulation to be significantly higher (p < 0.05) in the drug user compared to drug-free HIV-1(+). Drug abuse may alter the change from the (CD4+)CD45RA+ to the (CD4+)CD45RA- phenotype selectively, which recovers in HIV-1+ methamphetamine abusers during treatment from baseline to 4-weeks, as manifested by improved IL-2 production in vitro. of TH1 and TH2 cytokines during progression to AIDS.