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Higher Dose Flu Vaccine Works Better for People with HIV


HIV positive people who received a quadruple dose of a trivalent seasonal influenza vaccine produced more protective antibodies without a significant increase in side effects, researchers reported in the January 1, 2013, Annals of Internal Medicine.

People with HIV may be more susceptible to and prone to complications from certain types of influenza, and are therefore advised to receive an annual flu vaccine each year. However, individuals with impaired immune function may have difficulty mounting an adequate antibody response after vaccination.

Noah McKittrick from the University of Pennsylvania Center for AIDS Research

and colleagues compared the immunogenicity -- or ability to stimulate an immune response -- of a standard dose versus a high dose of a trivalent inactivated vaccine designed to protect against 3 strains: H1N1 influenza A, H3N2 influenza A, and influenza B.

This double-blind controlled trial enrolled 195 adult participants at the University of Pennsylvania hospital in Philadelphia between October 2010 and March 2011. Participants were randomly assigned (1:1) to receive single intramuscular injections of either a standard-dose formulation (15 mcg of antigen per flu strain) or ahigh-dose formulation (60 mcg per strain) of the Fluzone vaccine. The high-dose formulation was approved in 2009 for people over age 65, who also may have difficulty producing enough antibodies.

About 70% of participants were men and the median age was 45 years, with a good representation of white and black patients. Nearly 90% were on stable antiretroviral therapy (ART) -- mostly with suppressed HIV viral load -- while the rest were not yet on ART and not planning to start during the next month. The median current CD4 T-cell count was approximately 445 cells/mm3, but the nadir or lowest-ever level was about 170 cells/mm3, indicating considerable immune impairment. About half had protective H1N1 and influenza B titers at baseline, likely reflecting the high flu vaccination rate in 2009.

The primary efficacy endpoint was the proportion of people who achieved seroprotection, or sufficient antibody production 21-28 days after vaccination (defined as antibody titers of 1:40 or greater on a hemagglutination inhibition assay). The researchers also looked at the rate of seroconversion (> 4-fold increase in antibody concentrations) and average antibody titers. The primary safety endpoint was frequency and intensity of adverse events.

190 participants who completed the study (93 in the standard-dose group and 97 in the high-dose group) were included in the efficacy analysis, while all 195 were included in the safety analysis.


  • Seroprotection rates after vaccination were greater in the high-dose group compared with the standard-dose group for all 3 flu strains in the vaccine:

o   H1N1: 87% standard-dose vs 96% high-dose (P = 0.029);

o   H3N2: 92% vs 96%, respectively (P = 0.32);

o   Influenza B: 80% vs 91%, respectively (P = 0.030).

  • Likewise, seroconversion rates were also higher in the high-dose compared with the standard-dose group:

o   H1N1: 59% standard-dose vs 75% high-dose (P= 0.018);

o   H3N2: 74% vs 78%, respectively;

o   Influenza B: 34% vs 56%, respectively.

  • For both comparisons, the differences were significant for H1N1 and influenza B, but responses were statistically similar for H3N2.
  • The high-dose vaccine also appeared more effective for participants with fewer than 200 cells/mm3, but the number of such patients was too small to determine significance.
  • Both vaccine doses were described as "well-tolerated," with similar frequency of adverse events in both dose groups and no serious adverse events related to vaccine administration.
  • The most common side effects were myalgia or muscle aches (18% standard-dose vs 19% high-dose), malaise (15% vs 13%, respectively), and localized tenderness at the injection site (11% vs 10%); localized pain was more frequent in the high-dose group, however (4% vs 15%, respectively).

Based on these findings, the study authors wrote, "HIV-infected persons reach higher levels of influenza seroprotection if vaccinated with the high-dose trivalent vaccine than with the standard-dose."

"The results from this randomized, controlled study suggest that 1 way to increase the protective antibody titers for influenza in HIV-infected persons is to administer a higher dose (60 mcg/antigen -- 4 times the standard dose of 15 mcg/antigen) of the trivalent seasonal influenza vaccine," they elaborated in their discussion. "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 cautioned that the study did not evaluate whether participants were protected against clinical influenza. Also, the number of people with CD4 counts below 200 cells/mm3 was small, and this group might have a lower vaccine response rate due to extensive immune system impairment.

"This study suggests that a substantial number of HIV-infected patients may not be obtaining sufficient protection with the standard influenza vaccine," they concluded. "A strategy with a single high-dose immunization is much easier to implement than a multiple-dose schedule. Although a higher dose is 1 route to the protection of this vulnerable population, other strategies may also be explored in the future, such as alternative vaccines, the use of adjuvants, or new schedule strategies."



N McKittrick, I Frank, JM Jacobson, P Tebas, et al. From Improved Immunogenicity With High-Dose Seasonal Influenza Vaccine in HIV-Infected Persons: A Single-Center, Parallel, Randomized Trial. Annals of Internal Medicine 158(1):19-26. January 1, 2013.