Individuals infected with HIV are at higher risk for severe cases of seasonal influenza infection and should receive annual doses of vaccine. Our objectives were to evaluate the immunogenicity of an influenza vaccine in 37 HIV-infected patients (HIV group) compared to 29 uninfected individuals (control group) and to carry out a clinical and virological surveillance of influenza during a 6-month follow-up. Both groups received the vaccine recommended for the southern hemisphere in 2008. Antibody responses to antigens H1N1, H3N2, and B were measured in blood samples at vaccination (T0) and after 1 month (T1). Influenza surveillance was performed by weekly telephone calls for a follow-up period of 6 months. Nasal washes were taken from subjects with respiratory symptoms. The direct immunofluorescence assay in house polymerase chain reaction (PCR) and real-time PCR were used for the detection of different respiratory viruses. The median age of the participants was 13.3 years (sd = 2.2) and 12.1 years (sd = 1.3) for the HIV group and control group, respectively. One month after vaccination (T1), both groups showed significant increases in the antibody geometric mean titers (GMTs) for all antigens. However, healthy controls showed higher values for antigens A/H1N1 and A/H3N2 (p = 0.002 and 0.001, respectively). There was a higher increase in the percentage of HIV-uninfected subjects with protective A/H1N1 antibodies (96.6%) compared to HIV-infected vaccinees (67.6%) at T1 (p = 0.004). Rhinovirus (27.7%) and coronavirus (22.5%) were the most prevalent agents identified in HIV-infected individuals. In the control group, the viruses most frequently found were rhinovirus (24.2%) and adenovirus (21.2%). The seroprotection rate for the H1N1 antigen was higher in the control group, which also showed a greater increase in GMTs for H1N1 and H3N2 antigens after immunization. Viral agents were identified in 39/60 (65%) episodes of respiratory infections from the HIV-infected group and in 17/32 episodes (53.1%) from the control group (p = 0.273).