Flu Vaccine at Quadruple Dose Needed for Those With HIV

Yael Waknine

January 02, 2013

A quadruple-dose vaccine may be the answer for protecting patients with HIV from seasonal influenza, according to results from a study published in the January 2013 issue of the Annals of Internal Medicine.

For the study, Noah McKittrick, MD, and colleagues from the University of Pennsylvania and Drexel University in Philadelphia, randomly assigned 190 HIV-positive adults receiving stable antiretroviral therapy to receive either a standard dose (15 μg/strain) or a high dose (60 μg/strain) of trivalent influenza vaccine.

Results at 21 days revealed that for H1N1, the high-dose influenza vaccine yielded a significantly increased antibody response relative to baseline compared with the standard-dose injection (day 21: geometric mean titre [GMT] ratio, 2.0; 95% confidence interval [CI], 1.2 - 3.3 vs baseline: GMT ratio, 1.1; 95% CI, 0.4 - 1.8; P = .008), H3N2 (day 21: GMT ratio, 2.3; 95% CI, 1.4 - 3.7 vs baseline: GMT ratio, 1.0; 95% CI, 0.5 - 1.8; P = .001), and influenza B (day 21: GMT ratio, 2.2; 95% CI, 1.4 - 3.3 vs baseline: GMT ratio, 1.2; 95% CI, 0.5 - 1.4; P < .001).

A similar effect was observed with respect to seroconversion rates and seroprotection rates for H1N1 (75% vs 59% [P = .018] and 96% vs 87% [P = .029] for high dose and standard dose, respectively), H3N2 (78% vs 74% [P = .50] and 96% vs 92% [P = .32] for high dose and standard dose, respectively), and influenza B (56% vs 34% [P = .003] and 91% vs 80% [ P = .030] for high dose and standard dose, respectively). Both vaccines were equally well-tolerated, though pain was more often reported with the high-dose version (15% vs 4%).

The researchers acknowledge the main limitation of their study, which mirrors other influenza vaccine trials in those who are immunosuppressed; namely, that serologic response was measured rather than the incidence of clinical influenza. The latter would require a much larger sample size.

In addition, "[the] high baseline seropositivity rate may have contributed to the very high seroprotection rate at the end of our study," the authors note, attributing the high (50%) proportion of participants with protective titers at baseline to the increased rate of vaccination associated with the 2009-2010 pandemic and the fact that patients with HIV are more frequently engaged in care than other underserved populations.

"The implications of this research are important for future vaccination efforts in the HIV-positive population," the authors conclude, noting that although a single high-dose immunization strategy is much easier to implement than multiple-dose schedules, further study may yield additional options such as alternative vaccines, use of adjuvants, or new schedule strategies.

The study was supported by grants from the National Institute of Allergy and Infectious Diseases and the Center for AIDS Research to the University of Pennsylvania. Dr. McKittrick has disclosed no other relevant financial relationships. Full conflict-of-interest information is available on the journal's Web site.

Ann Intern Med. 2013;158:19-26. Abstract