The objective of this study was to analyze the relationships between adherence to treatment and sexual and drug-taking behaviors among persons with HIV, who started combination antiretroviral therapy as their first regimen. The authors analyzed data from 366 patients enrolled in a multicenter observational cohort study conducted in infectious disease hospital units in Italy. Adherence measurement was based on responses to a self-administered questionnaire regarding following HIV physician advice on taking medications and missed appointments. Questions on sexual and drug-taking behaviors were also included in the questionnaire. The median time since starting antiretroviral therapy was 11.8 months; 37.4% of patients were on a two-drug regimen and 62.6% were on a three-drug regimen. Overall, 68 patients (18.6%) could be classified as nonadherent. The proportion of patients with viral load < or = 500 copies/mL was significantly higher among adherent patients (68%) compared with nonadherent patients (40.4%; p = .001). In multivariable analysis, age (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.42-0.98, per 10-year increment) and current use of injection (OR, 3.47; 95% CI, 1.40-8.5) or noninjection drugs (OR, 4.23; 95% Cl, 1.85-9.67) were significantly associated with nonadherence. No significant association was found between adherence and sexual behaviors. The data do not support the hypothesis that among HIV-infected person on antiretroviral therapy, poor adherence is associated with high-risk sexual behaviors that may further spread the infection.