CD4-mediated immunity is the major host defense mechanism against C. albicans. We here investigated a group of ART naïve, HIV-infected human subjects and examined longitudinally the impact of HIV on C. albicans-specific CD4 T-cell immunity as compared to CD4 T-cell immunity specific for CMV, another opportunistic pathogen that usually does not cause active disease in early HIV infection. Here, CD4 is linked to HIV infectious disease.