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More Flu Vaccine Better in HIV, Study Finds
Patients with HIV received greater seroprotection against the flu when they received four times the normal dose of flu vaccine compared with standard doses, a study found.
Note that both high and standard doses were well-tolerated, with similar adverse event profiles.
Patients with HIV received greater seroprotection against the flu with four times the normal dose of flu vaccine, researchers found.
Compared with HIV patients who received normal doses of the flu vaccine, seroprotection was 9 percentage points higher for H1N1 (95% CI 1 to 17, P=0.029) and 11 percentage points higher for influenza B (95% CI 1 to 21, P=0.03), and was a nonsignificant 3 percentage points higher for H3N2 in those receiving the higher dose, according to Pablo Tebas, MD, of the University of Pennsylvania in Philadelphia, and colleagues.
"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," they wrote online in the Annals of Internal Medicine.
Both high and standard doses were well tolerated with similar adverse event profiles, they noted.
Although seasonal influenza vaccine has been shown to provide an estimated protective efficacy of 70% to 90% in healthy adults, "several studies have shown that antibody responses ... in HIV-infected persons are lower than in the general population, although this finding has not been consistent across all studies," the authors noted in their introduction. "It is necessary to evaluate strategies that increase the efficacy of influenza vaccination in HIV-infected persons."
To investigate the issue, the authors studied whether increasing the doses of influenza vaccine would have increased efficacy compared with standard dosing among 190 HIV-infected patients older than 18 years with an indication for receiving the flu vaccine, who were receiving stable antiretroviral therapy, or who were not receiving antiretroviral therapy and did not intend to start from 30 days after study baseline.
Participants were randomized to either 15 mcg of antigen per strain (93 patients) -- the standard dose -- or 60 mcg per strain (97 patients) of an influenza trivalent vaccine (Fluzone).
Outcomes included proportion of participants with seroprotective antibody levels at 21 to 28 days after vaccination, frequency and severity of adverse events up to 28 days after vaccination, seroconversion rate, and concentrations of serum hemagglutination inhibition before and after vaccination.
Seroprotection was defined as 1 part per 40 parts antibody concentrations at 21 to 28 days, while seroconversion was defined as a greater-than four-fold increase in antibody concentrations.
Participants had CD4 cell, HIV viral load, and influenza antibody counts taken at baseline, with follow-up flu virus antibody counts taken at 21 to 28 days after vaccination for strains H1N1, H3N2, and influenza B.
Adverse event data were collected at the 21- to 28-day follow-up, as well as by phone on days four and 10 of follow-up from vaccination.
At baseline, roughly half of participants in both groups had seroprotective antibody concentrations for H1N1 (49% of those in the high-dose group and 52% of those in the standard-dose group) and influenza B (49% and 52%, respectively), while more than half of the standard-dose participants had protective concentrations of H3N2 antibodies (52%) and less than half of high-dose participants had protective concentrations against H3N2 (44%).
Serum hemagglutination inhibition concentrations were similar for the three antigens at baseline between groups, but mean postvaccination concentrations in the high-dose group were roughly double those of the standard-dose group for the H1N1 (686 versus 344), H3N2 (739 versus 324), and influenza B strains (140 versus 64).
At the 21 to 28 day follow-up, the high-dose vaccine was more immunogenic overall, though the difference between groups in immunogenicity was only significant for H1N1 and influenza B (P=0.029 and P=0.03, respectively). Seroconversion rates were significantly higher for participants in the high-dose group for H1N1 (75% versus 59%, P=0.018) and influenza B (56% versus 34%, P=0.003), but not for H3N2 (78% versus 74%, P=0.5).
A separate, exploratory analysis found that patients with CD4 cell counts less than 0.200 x 109 cells/L were less responsive to both high- and standard-dose vaccines, and fewer patients developed seroprotective antibody levels.
Rates of the most common adverse events were similar between groups, including:
Tenderness: 10% of high-dose participants versus 10.5% of standard-dose participants
Malaise: 13% versus 14.7%
Myalgia: 19% versus 17.9%
The overall number of systemic adverse events was the same between groups (60%), while local adverse events were more common among those in the high-dose group (30% versus 16.8%), particularly comparing incidents of pain between groups (15% of high-dose participants versus 4.2% of standard-dose participants).
The authors noted that single, high-dose immunization outperformed standard doses of trivalent flu vaccine, and that future studies could explore new schedule strategies, alternative vaccines, or use of adjuvants.
The study was limited by low sample size, limited power in detecting different effects of vaccine doses, and high baseline seropositivity rates.