Predictors of seasonal influenza vaccine immunogenicity in HIV infected adults
C. Cooper1, M. Klein2, A. Thorne3, B. Conway4, M. Smieja5, A. Rachlis6, M. Harris4, A. Markanday7, J. Singer3, G. Boivin8, S. Walmsley6, The CIHR Canadian HIV Trials Network (CTN) Influenza Vaccine Research Group
1University of Ottawa, Infectious Diseases, Ottawa, Canada, 2McGill University, Montreal, Canada, 3The CIHR Canadian HIV Trials Network, Vancouver, Canada, 4University of British Columbia, Vancouver, Canada, 5McMaster University, Hamilton, Canada, 6University of Toronto, Toronto, Canada, 7Western University of Health Sciences, London, Canada, 8Laval University, Laval, Canada
Background: More severe influenza disease and poor vaccine efficacy in HIV necessitate improved immunization strategies to maximize vaccine efficacy.
Methods: A phase III vaccine trial was conducted at 12 CTN sites. Three dosing strategies were assessed in HIV-infected adults (18-60 years) prior to the 2008-09 influenza season. A seasonal, trivalent killed split non-adjuvanted influenza vaccine (Fluviral) was utilized. Subjects were randomized 1:1:1 to receive vaccine at baseline +/- day 28 as two standard doses; two double doses; or a single standard dose. Predictors of hemagglutinin inhibition (HAI) titre doubling, quadrupling and seroprotection (≥40) were assessed by multivariable logistical regression controlling for treatment group, cART use, HIV viral load, baseline CD4 count, nadir CD4, time since nadir, age, sex, weight, tobacco use, HCV co-infection, and prior influenza vaccination.
Results: 297 participants received at least one injection. Baseline parameters included: 90% male, 89% on cART, median CD4 = 470 cells/mm3, median nadir CD4=189 cells/mm3, 76% with HIV RNA < 50 copies/mL, and 84% had received flu vaccine the previous year.
At week 8, double dose plus booster recipients were more likely to achieve HAI doubling for A/Brisbane (H1N1) [OR=2.4 (1.3-4.4), p< 0.01] and B/Florida [1.9 (1.0-3.5), p=0.04] and quadrupling for A/Brisbane [2.2 (1.1-4.3), p=0.03] as well as week 20 quadrupling for A/Uruguay (H3N2) [2.2 (1.1-4.7), p=0.03].
Baseline HAI titre >1:10 was highly predictive of seroprotection at weeks 8 and 20 (all antigens), doubling of titres at week 8 (all), and doubling of titres at week 20 (A/Uruguay and B/Florida). Female sex predicted week 8 HAI doubling for A/Brisbane [4.8 (1.7-13.3), p< 0.01] and B/Florida [2.7 (1.2-6.3), p=0.02] and quadrupling for A/Brisbane [4.0 (1.8-9.2), p< 0.001] and A/Uruguay [3.7 (1.6-8.3), p< 0.01]. No other consistent immunogenicity predictors were identified.
Conclusions: Yearly provision of increased antigen dose plus booster improves vaccine immunogenicity to circulating influenza strains in HIV.
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