HealthDay News — Adults with HIV achieved higher rates of seroprotection when immunized with a dose of  trivalent influenza vaccine four times the strength of the standard dose, study findings show.

Compared with patients who received normal doses of the flu vaccine, seroprotection was 9 percentage points higher for H1N1 (95% CI: 1-17, P=0.029) and 11 percentage points higher for influenza B (95% CI: 1-21, P=0.03) in those receiving the higher dose, Noah McKittrick, MD, from University of Pennsylvania in Philadelphia, and colleagues reported in Annals of Internal Medicine. Seroprotection was a nonsignificant 3 percentage points higher for H3N2 in those receiving the higher dose.

“For every antigen studied, the high-dose formulation resulted in an increased average antibody titer and higher seroconversion and seroprotective rates compared with the standard-dose influenza vaccine,” the researchers wrote.

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Findings from several previous studies suggest that antibody responses to influenza vaccine may be lower among patients with HIV than healthy patients, but this finding has not been consistent across numerous studies.

To better understand the efficacy of influenza vaccination in this group of patients, McKittrick and colleagues assessed rates of seroprotection among 190 adults with HIV.  Seroprotection was defined as antibody titers of 1:40 or greater on hemagglutination inhibition assay. Seroconversion, defined as a greater than four-fold increase in antibody titers, and the geometric mean antibody titer were also assessed.

Patients were randomly assigned to either the standard dose (15 mcg of antigen per strain; 93 participants) or a high dose (60 mcg/strain; 97 participants) of trivalent influenza vaccine. CD4 cell, HIV viral load, and influenza antibody counts were assessed at baseline and follow-up flu virus antibody counts were taken at 21 and 28 days after vaccination. Serum hemagglutination inhibition concentrations were similar for the three antigens at baseline between groups. 

Mean postvaccination concentrations in the high-dose group were roughly double those of the standard-dose group for the H1N1 (686 vs. 344), H3N2 (739 vs. 324), and influenza B strains (140 vs. 64), the researchers found.

Seroprotection rates were higher for H1N1 (96% vs. 87%; P = 0.029), H3N2 (96% vs. 92%; P = 0.32), and influenza B (91% vs. 80%; P = 0.030) strains, although the findings were only statistically significant for H1N1 and influenza B. Similarly, seroconversion rates were significantly higher for participants in the high-dose group for H1N1 (75% vs. 59%, P=0.018) and influenza B (56% vs. 34%, P=0.003), but not for H3N2 (78% vs. 74%, P=0.5).

Both standard- and high-dose vaccines were well tolerated, with myalgia (19%), malaise (14%), and local pain (10 %) among the most frequently reported adverse events in both the low- and high-dose groups.

The overall number of systemic adverse events was the same between groups (60%). However, local adverse events were more common among patients in the high-dose group (30% vs. 16.8%), particularly incidents of pain between groups (15% in the high-dose group vs. 4.2% in the standard-dose group).

“The implications of this research are important for future vaccination efforts in the HIV-positive population,” the authors write. “This study suggests that a substantial number of HIV-infected patients may not be obtaining sufficient protection with the standard influenza vaccine.”

Study limitations included low sample size and high baseline seropositivity rates. Future studies should explore new vaccine schedule strategies, alternative vaccines or the use of adjuvants to adequately immunize patients with HIV against influenza.


  1. Tebas P et al. Ann Intern Med. 2013:158(1); 19-26.