ABSTRACT: OBJECTIVE:High-density lipoprotein (HDL) function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic treated HIV-1 infection. DESIGN:Retrospective study of HDL function measured in 2 ways in HIV-1-infected men with low overall CVD risk and healthy men with no known CVD risk matched by race to the HIV-1-infected participants. METHODS:We examined patient-level factors associated with 2 different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were used adjusting for false discovery rate, age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, and albumin. RESULTS:In multivariate analysis among HIV-1-infected men (n = 166) (median age 45 years, CD4 T-cell count 505 cells/mm, 30.1% were viremic), higher BMI, lower apoA-I, and lower albumin were among the most notable correlates of higher HDLox and lower HAE (P < 0.05). In HIV-1 uninfected participants, lower albumin and higher BMI were associated with lower HAE and higher HDLox, respectively (P ? 0.05). HDLox was inversely related to HAE in HIV-1-infected individuals (P < 0.001). CONCLUSIONS:Increased HDLox correlates with reduced HAE in chronic HIV-1 infection. Higher BMI, lower apoA-I, and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection using 2 independent methods.