H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses

Abstract

Background Since human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. Methodology/Principal Findings Open label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD4<200 cells/mm 3 was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. Conclusions/Significance Our results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD4<200 cells/mm 3 , to achieve antibody levels that are both higher and more sustained. Trial Registration ClinicalTrials.gov NCT01155037

Immunogenicity and sustainability of the immune response in Brazilian HIV‐1‐infected individuals vaccinated with inactivated triple influenza vaccine

“…Participants were approached for study participation from March through August 2011. The sample size was then defined according to criteria presented elsewhere [Santini‐Oliveira et al, ]. All 256 patients included in the 2010 were targeted for immunization and serological assessment in 2011.…”

“…Inclusion criteria for all participants were age 18–59 years and participation in the phase 1 of our investigation [Santini‐Oliveira et al, ], when HIV‐infected individuals received monovalent vaccine against influenza A(H1N1)pdm09. The main exclusion criteria were: receipt of another investigational vaccine or drug in the past 4 weeks, previous anaphylaxis or serious reactions to vaccines, or hypersensitivity to egg and chicken protein or ovalbumin, neurological illness, acute illness on the day of enrolment, pregnancy and breastfeeding.…”

“…We had previously performed an open labeled, randomized, phase‐II trial to monitor the immunogenicity and sustainability of immune response against the influenza A(H1N1)pdm09 [Santini‐Oliveira et al, ]. In the present investigation, a subset of individuals enrolled in the first phase of our investigation [Santini‐Oliveira et al, ] were included.…”

British HIV Association Guidelines on the Use of Vaccines in HIV‐Positive Adults 2015

“…One other study comparing HIV‐positive and HIV‐negative individuals suggested merely quantitative differences in the vaccine responses, thus offering a rationale for boosting strategies in the HIV‐positive population . In HIV‐positive adults however, administering higher/more frequent doses of standard non‐adjuvanted vaccine preparations has not been consistently associated with improved immunogenicity, whilst enhanced responses have been observed with novel adjuvanted preparations . Data on the clinical efficacy of influenza vaccination in HIV‐positive adults are limited.…”

“…Inactivated influenza vaccines are safe and well tolerated in HIV‐positive individuals . Injection site reactions are the most frequent side effects.…”