OBJECTIVE: Complaints of dry skin in HIV-infected individuals were reported after the advent of HAART. The objective of the study was to evaluate the prevalence of dry skin and associated factors in HIV-infected and control subjects. DESIGN: Cross-sectional. METHODS: A total of 1026 HIV-infected subjects and 274 controls [from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based study of cardiovascular risk assessment] in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) had skin assessed by self-report and examination. Multivariable logistic regression identified factors associated with dry skin. RESULTS: Self-reported dry skin was more prevalent in HIV-infected subjects than controls. In multivariable analysis, HIV infection was associated with self-reported dry skin. In HIV-infected men, current indinavir use, CD4 cell count less than 200 cells/μl and recent opportunistic infections were associated with dry skin. Indinavir use had an elevated risk in men with CD4 cell counts of 200 cells/μl or greater but not with CD4 cell counts less than 200 cells/μl. In HIV-infected women, a CD4 cell count less than 200 cells/μl was associated with dry skin; indinavir use did not reach statistical significance but, as in men, indinavir use had an elevated risk in those with higher CD4 cell counts than in those with CD4 cell counts less than 200 cells/μl. CONCLUSION: Dry skin is more common in HIV-infected individuals than controls. In HIV-infected individuals, low CD4 cell counts and indinavir use in those with higher CD4 cell counts are associated with dry skin. © 2007 Lippincott Williams & Wilkins, Inc.