OBJECTIVES: HIV-infected adults are considered to be at higher risk for influenza A H1N1 complications but data supporting this belief are lacking. We aimed to compare epidemiological data, clinical characteristics, and outcomes of influenza A H1N1 infection between HIV-infected and -uninfected adults. METHODS: From 26 April to 6 December 2009, each adult presenting with acute respiratory illness at the emergency department of our institution was considered for an influenza A H1N1 diagnosis by specific multiplex real-time polymerase chain reaction. For every HIV-infected adult diagnosed, three consecutive adults not known to be HIV-infected diagnosed in the same calendar week were randomly chosen as controls. RESULTS: Among 2106 adults tested, 623 (30%) had influenza A H1N1 infection confirmed. Fifty-six (9%) were HIV-positive and were compared with 168 HIV-negative controls. Relative to HIV-negative controls, HIV-positive patients were older, more frequently male, and more frequently smokers (P≤0.02). In the HIV-positive group, prior or current AIDS-defining events were reported for 30% of patients, 9% and 30% had CD4 counts of <200 and 200-500cells/µL, respectively, and 95% had HIV-1 RNA <50copies/mL. Pneumonia (9%vs. 25%, respectively, in the HIV-positive and HIV-negative groups; P=0.01) and respiratory failure (9%vs. 21%, respectively; P=0.04) were less common in the HIV-positive group. Oseltamivir (95%vs. 71% in the HIV-positive and HIV-negative groups, respectively; P=0.003) was administered more often in HIV-positive patients. Three patients (all HIV-negative) died. In the HIV-positive group, CD4 cell count and plasma HIV-1 RNA did not differ before and 4-6 weeks after influenza A H1N1 diagnosis (P>0.05). CONCLUSIONS: HIV infection did not increase the severity of influenza A H1N1 infection, and influenza A H1N1 infection did not have a major effect on HIV infection.