OBJECTIVE: To estimate the independent association between socioeconomic conditions and the risk of all-cause hospitalization or death during the course of HIV disease in the highly active antiretroviral therapy (HAART) era. METHODS: Patients in the French PRIMO multicenter prospective cohort of 319 individuals were enrolled during primary HIV-1 infection between 1996 and 2002. Associations between social characteristics (ie, employment status, stable partnership) and the risk of hospitalization or death were assessed using generalized estimating equations. RESULTS: During a median follow-up of 2.5 years, 109 hospitalizations among 84 patients (26.3%) and 3 deaths occurred. Even after adjustment for classic determinants of HIV-infected patients' health status, social characteristics were independently associated with the risk of hospitalization or death, with a significantly increased risk for patients with temporary employment compared with those with stable employment (adjusted odds ratio [OR] = 2.5, 95% confidence interval: 1.1 to 5.6) and for patients without a stable partnership compared with those with a stable partnership (OR = 1.6, 95% confidence interval: 1.0 to 2.7). CONCLUSIONS: In the era of HAART, adverse social conditions constitute independent risk factors of hospitalization or death during the course of HIV disease.