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Efficacy and immunogenicity of influenza vaccine in HIV-infected children: a randomized, double-blind, placebo controlled trial

Madhi, Shabir A.a,b,c; Dittmer, Sylviad; Kuwanda, Locadiahb,c; Venter, Marietjiea; Cassim, Haseenad; Lazarus, Ericad; Thomas, Teenad; Liberty, Afaafd; Treurnich, Florettea; Cutland, Clare L.b,c; Weinberg, Adrianae; Violari, Avyd

doi: 10.1097/QAD.0b013e32835ab5b2
Clinical Science

Background: HIV-infected children are at heightened risk for severe influenza illness; however, there is no study on the efficacy or effectiveness of influenza vaccine in these children. We evaluated the safety, immunogenicity, and efficacy of nonadjuvanted, trivalent inactivated influenza vaccine (TIV) against confirmed seasonal influenza virus illness in HIV-infected children.

Methods: A double-blind, placebo-controlled trial was undertaken in Johannesburg in 2009. Four hundred and ten children were randomized to two doses of TIV or placebo 1 month apart. Nasopharyngeal aspirates obtained at respiratory illness visits were tested by influenza-specific reverse transcriptase-PCR (RT-PCR). Vaccine immunogenicity was evaluated by hemagglutinin inhibition (HAI) assay. Influenza isolates were sequenced and evaluated in maximum likelihood phylogenetic analysis.

Results: Overall, the median age of participants was 23.8 months and their median CD4% was 33.5. Ninety-two percent of enrolees were on antiretroviral therapy. Among children receiving both doses of vaccine/placebo, confirmed seasonal influenza illness occurred in 13 (all H3N2) of 205 TIV recipients and 17 (15 H3N2 and two influenza B) of 200 placebo recipients with vaccine efficacy of 17.7% (95% confidence interval <0–62.4%). The proportion of TIV recipients who seroconverted after second dose against vaccine strains of H1N1, H3N2, and influenza B were 47.5, 50.0, and 40.0%, compared to 4.7, 11.6, and 0%, respectively among placebo recipients. There were no TIV-related serious adverse events. Sequence analysis of wild-type H3N2 strains indicated drift from the H3N2 vaccine strain.

Conclusion: Poor immunogenicity of TIV, coupled with drift of circulating H3N2 wild-type compared to vaccine strain, may explain the lack of efficacy of TIV in young HIV-infected children. Alternate TIV vaccine schedules or formulations warrant evaluation for efficacy in HIV-infected children.

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aNational Institute of Communicable Diseases, Centre for Respiratory and Meningitis Diseases, Sandringham

bDepartment of Science and Technology/National Research Foundation, Vaccine Preventable Diseases

cMedical Research Council: Respiratory & Meningeal Pathogens Research Unit

dPerinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa

eDepartment of Pediatrics, Medicine and Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado, USA.

Correspondence to Shabir A. Madhi, National Institute for Communicable Diseases, National Health Laboratory Service, 1 Modderfontein Road, Sandringham, 2131 Johannesburg, Gauteng, South Africa. Tel: +27 113866137; e-mail:

Received 16 August, 2012

Revised 21 September, 2012

Accepted 24 September, 2012

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© 2013 Lippincott Williams & Wilkins, Inc.