Pandemic influenza vaccine in adult HIV-1-infected patients

International [1] and national [2] guidelines suggest that a single shot of adjuvanted vaccine is sufficient to protect immunosuppressed HIV-infected patients aged less than 60 years from the H1N1 pandemic influenza in the season 2009–2010. Bickel and co-workers [3] report a low seroconversion rate (69%) 21 days after vaccination with a split virion, AS03 adjuvanted pandemic H1N1 vaccine containing 3.75 μg antigen in a cohort of 160 HIV-infected patients and suggest the need to investigate whether a second dose of the vaccine will increase the seroconversion rate. Here, we report our preliminary experience on immunogenicity of a single-shot monovalent MF59-adjuvanted influenza A/California/2009(H1N1) surface-antigen vaccine containing 7.5 μg of hemagglutinin in HIV-infected outpatients attending the Department of Infectious Diseases - L Sacco University Hospital, Milan (Italy). Among 496 HIV-infected patients, vaccinated according to guidelines defined by Italian Ministry of Health in the period October to December 2009, 253 consenting patients were evaluated for anti-H1N1 antibody titers measured by hemagglutination-inhibition assay (HIA) on day 0 and after vaccine [median time 21 days, interquartile range (IQR) 21–26 days]. Patients included in this analysis (75 women and 177 men) had a mean age of 46.65 ± 9.5 years, a median time from the HIV diagnosis of 12.15 ± 7.8 years and were mainly on highly active antiretroviral therapy (HAART) regimens (90.56%). They had experienced a mean of 4.2 ± 3.6 antiretroviral treatments, had a mean CD4 cell count of 569.7 ± 265.9 cells/μl and a mean viral load of 1.9 ± 0.78 log10 copies/ml with a suppressed viremia in 82.05% of the cases. On baseline evaluation 67 (26.48%) had HIA titers of at least 1: 40; this high rate of prevaccine protective antibody titers could be explained by the late vaccine distribution when the pandemic wave has already reached the peak in Italy (reported on November/December 2009) [4]. Seroconversion, defined as HIA titer of at least 1: 40 and a four-fold increase in H1N1 antibody titers from baseline, was achieved in 209/253 (82.61%), with the overall proportion of patients with titers of at least 1: 40 being 92.49% (234/253). Antibody titers, expressed as geometric means, increased from a median value of 5 (IQR 5–40) to 160 (IQR 80–320) (Mann–Whitney test P < 0.0001). Immuno-virological and clinical characteristics of seroconverters or of patients who generated protective titers antibody responses for natural infection and/or vaccine are compared with nonseroconverters or patients with antibody titers less than 1: 40 (Table 1).Table 1: Immuno-virological and clinical characteristics of seroconverters or patients with antibody titers of at least 1: 40 compared to nonseroconverters or patients with antibody titers less than 1: 40 within 21 days after vaccination.Patients with a longer lasting infection (>2 years) had a higher probability of seroconversion compared to those with a recent diagnosis of HIV infection [odds ratio (OR) 3.79 with 95% confidence interval (CI) 1.44–10.01]. Sex, age, number of previously experienced antiretroviral regimens, mean CD4 and HIV viral load, class of CD4, having a suppressed HIV viral load, being on/off HAART, did not affect the seroconversion rate. Higher CD4 cells were observed in patients with antibody titers of at least 1: 40 and patients with CD4 cells more than 500/μl showed a 6.35 (95% CI 1.42–28.44)-fold higher probability of a protective titer of anti-H1N1 antibodies after vaccine than those with a lower CD4 cell count. Patients on HAART regimens were more probably protected than those off HAART (OR 3.38, 95% CI 1.0–11.47). Patients with protective antibody levels had a significantly longer lasting HIV infection (Mann–Whitney test P = 0.0038). Considering both the naturally and/or vaccine-induced protective titers (≥1: 40 measured on day 21) and only the vaccine-induced seroconversion rate, our preliminary results show that a single-shot monovalent influenza A(H1N1)2009 MF59-adjuvanted vaccine generates antibody responses possibly associated with protection within 21 days in successfully HAART-treated HIV-infected adults, with rates comparable to those achieved in healthy adults [5], and at a higher rate than those reported by Bickel and co-workers [3]. How long protective antibody titers can be detected after one single vaccine injection in HIV-infected patients is under evaluation. Acknowledgement We would like to thank all the medical and nurse staff of the Department of Infectious Diseases, L Sacco University Hospital, Milan for their contributions to this study.