Background:  Immune responses to vaccines are often impaired by HIV infection. HAART improved virologic and immunologic outcomes in treated children; however, it is unclear whether specific immune responses to vaccine antigens are also restored. We evaluated influenza-specific humoral and cell-mediated immune responses upon vaccination in HIV-infected children on long-term successful HAART.

Methods:  We studied 24 HIV-infected children (median age 11.9 years) on long-term HAART (mean exposure 85 months). Their mean (SD) CD4 number was 900 (259) cell/mL, mean (SD) CD4 percentage was 36.9 (9.1), and HIV RNA was <50 copies/mL. As a control group, we enrolled 14 healthy controls. Their median age was 10.2 years, mean (SD) CD4 number and percentage were 992 (407) cell/mL and 38.8 (4.1). All HIV⁺ and healthy controls were unprimed and immunized with a single intramuscular dose of trivalent virosome-adjuvanted influenza vaccine (Inflexal V). A/H3N2, A/H1N1, and B antigen specific antibody titres and vaccine specific interferon-gamma- (IFN-g-) and interleukin-2 (IL-2) -producing T lymphocytes (ELISpot) were analyzed at baseline and 1 and 6 months after immunization.

Results:  HIV⁺ and healthy controls were similar for age and CD4 count and percentage. Seroconversion ( >4 fold increase in antibody titres in >40% of subjects)  and seroprotection (antibody titres >1:40 in >70% of subjects) were defined, 1 month after immunization, according to the European Agency for Evaluation of Medical Products criteria. HIV⁺ and healthy controls fulfilled seroconversion (A/H3N2: 54.1 vs 71.4; A/H1N1: 70.8 vs 92.8; B: 70.8 vs 85.7) and seroprotection (A/H3N2: 79.2 vs 92.8; A/H1N1: 79.2 vs 92.8; B: 75.0 vs 92.8) criteria for all antigens. At baseline, antibody geometric means titres for all antigens were similar in HIV and healthy controls.  The A/H3N2- and A/H1N1-specific antibody geometric means titres were significantly (p <0.01) lower in HIV⁺ than healthy controls (44.90 vs 76.14; 146.72 vs 609.08) at 1 month. Similar results were observed at 6 months (29.11 vs 51.24; 109.92 vs 452.55). Vaccine specific-, IFN-g- and IL-2- producing T lymphocytes were reduced at 1 month in HIV⁺ compared to healthy controls (IFN-g, 104 vs 215 SFU, p = 0.007; IL-2, 20 vs 115 SFU, p = 0.01). The differences were even higher at 6 months.

Conclusions:  The virosome-adjuvanted influenza vaccine showed a comparable immunogenicity in HIV⁺ and healthy controls. However, functional impairment of immune responses persists in HIV infection even in children with suppressed viremia and immune recovery. These impairments result in the elicitation of suboptimal humoral and cellular response to immunization.