H1N1pdm09 adjuvanted vaccination in HIV-infected adults: a randomized trial of two single versus two double doses

Marilia Santini-Oliveira, Luiz A B Camacho, Thiago M L Souza, Paula M Luz, Mauricio T L Vasconcellos, Carmem B W Giacoia-Gripp, Mariza G Morgado, Estevão P Nunes, Alberto S Lemos, Ana C G Ferreira, Ronaldo I Moreira, Valdiléa G Veloso, Marilda M Siqueira, Beatriz Grinsztejn, Marilia Santini-Oliveira, Luiz A B Camacho, Thiago M L Souza, Paula M Luz, Mauricio T L Vasconcellos, Carmem B W Giacoia-Gripp, Mariza G Morgado, Estevão P Nunes, Alberto S Lemos, Ana C G Ferreira, Ronaldo I Moreira, Valdiléa G Veloso, Marilda M Siqueira, Beatriz Grinsztejn

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Participant disposition: enrollment, study procedures…
Figure 1. Participant disposition: enrollment, study procedures and participant disposition.
Figure 2. Reverse cumulative distribution curves of…
Figure 2. Reverse cumulative distribution curves of HAI antibody titers in samples collected on days 0, 21, 42, and at 6 months by vaccine group of participants: HIV-infected who received single doses (dashed line), HIV-infected who received double doses (solid line), and HIV-negative (dotted line).
Values are given on a log scale.
Figure 3. Adverse events: local and systemic…
Figure 3. Adverse events: local and systemic adverse events 21 days after first dose and 42 days after the first dose in the three groups: HIV-infected who received single doses, HIV-infected who received double doses, and HIV-negative.

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Source: PubMed

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