Randomized Controlled Trial to Compare Immunogenicity of Standard-Dose Intramuscular Versus Intradermal Trivalent Inactivated Influenza Vaccine in HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand

Abstract

Background Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. Methods We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard-dose (15 µg) ID vs standard-dose (15 µg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed. Results We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%). Conclusions There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIV-infected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed.

Immunogenicity and Safety of Reduced-Dose Intradermal vs Intramuscular Influenza Vaccines

“…Of 30 included studies, 29 studies were randomized clinical trials with a total of 13 759 participants, 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 and 1 study was a cohort study of 164 021 participants ( Table 1 ). 47 Sixteen studies were multi-center 18 , 19 , 20 , 22 , 23 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 43 , 44 , 47 ; 12 studies were single-center 24 , 25 , 26 , 27 , 28 , 30 , 32 , 35 , 36 , 39 , 40 , 45 ; and 2 studies did not repo...…”

“…Most studies had bias stemming from the randomization process; 6 studies were at low risk of bias 20 , 23 , 24 , 30 , 32 , 35 ; and 2 studies were at high risk. 28 , 34 All but 2 low-risk studies 23 , 35 had some risk of bias due to deviations from intended interventions.…”

“…Of 30 included studies, 29 studies were randomized clinical trials with a total of 13 759 participants, and 1 study was a cohort study of 164 021 participants (Table 1). 47 Sixteen studies were multi-center [18][19][20]22,23,29,31,33,34,37,38,41,43,44,47 ; 12 studies were single-center [24][25][26][27][28]30,32,35,36,39,40,45 ; and 2 studies did not report the setting. 21,42 Approximately half of the studies (14 studies) 18,19,21,22,[24][25][26][27]29,34,41,43,44,46 involved only participants aged 60 years or older or reported data for participants aged 60 years or older.…”

Intradermal versus Intramuscular Administration of Influenza Vaccination: Rapid Review and Meta-analysis

“…46 All studies were published between 2010 and 2019. Sixteen studies were multi-centre, 17-19 21 22 28 30 32 33 36 37 40 42 43 46 12 were single-centre, 23-27 29 31 34 35 38 39 44 and two studies did not report the setting. 20 41 Half of the studies involved only participants ≥60 years old or reported data for participants ≥60 years old.…”

“…The majority of the studies had some bias stemming from the randomization process; six studies were at low risk of bias; 19 22 23 29 31 34 and two studies were at high risk. 27 33 All but two low risk studies 22 34 had some risk of bias due to deviations from intended interventions.…”