As the days get shorter and cooler, you have an increasing sense of dread that Winter Is Coming – and with it comes flu season. Once you stop daydreaming of the halcyon days of summer, you notice that in your waiting room are two pregnant patients, one HIV positive, one HIV negative.
You take a moment to reflect on how best to advise both patients regarding the approaching dreaded flu season. Do recommendations differ for the two women? What evidence are these recommendations based on?
Data on the efficacy and safety of vaccines in pregnant women are surprisingly limited, and they are even more limited in pregnant women who are HIV-infected. Although pregnant women are at higher risk of severe influenza illness, especially from the second trimester of pregnancy until early post-partum, influenza vaccination rates in pregnancy were as low as 15%, but the rate has increased to about 50% since the 2009 H1N1 pandemic. There may be tendency to feel that avoiding medical interventions, even vaccination, is safer for the developing fetus. In this week’s NEJM, Dr. Madhi et al report the findings of two studies in HIV-infected and uninfected women in South Africa, seeking to provide some much-needed answers.
Two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccines (IIV3) investigated the immunogenicity, safety and vaccine efficacy of IIV3 in pregnant HIV-infected and uninfected pregnant women and their infants in Soweto, South Africa. The study included 2116 HIV uninfected and 194 HIV-infected pregnant women who were randomized to receive the IIV3 vaccine or placebo. Outcomes of immunogenicity, safety, and vaccine efficacy were compared between the two arms.
The investigators found higher one-month seroconversion rates in HIV-infected and uninfected vaccine recipients and their newborns compared to placebo. Significantly lower incidence of influenza illness was seen in HIV-uninfected vaccine recipients and their infants, with a vaccine efficacy of 50.4% [95%CI: 14.5% to 71.2%] and 48.8% [95%CI: 11.6% to 70.4%] respectively. Among HIV-infected vaccine recipients, vaccine efficacy was 57.7% [95%CI: 0.2% to 82.1%]. Vaccine efficacy in HIV-exposed infants was 26.7% [p=0.60], but the study lacked sufficient power to detect a significant difference in HIV-exposed infants. Higher proportions of HIV-infected and uninfected recipients experienced mild-moderate injection site reactions, but no other differences were found in rates of reactions or severe adverse events comparing vaccine recipients to non-recipients.
NEJM Deputy Editor Lindsey Baden states: ‘Protecting pregnant women and their infants from influenza infection and disease remains a high priority as these two groups are particularly vulnerable to severe complications from the flu. As the data from these studies show, influenza vaccination is a relatively simple way to achieve this.’
These data address key questions affecting this infrequently studied at-risk population and has significant public health implications. Demonstration of vaccine efficacy and safety supports the recommendation of the World Health Organization, and should encourage clinicians to work for an increased uptake of influenza vaccination among pregnant women, including both HIV-infected and uninfected.
In your clinical practice, how do you counsel pregnant women regarding influenza vaccination? What about HIV-infected pregnant women? What questions do you have regarding vaccination during pregnancy in these populations?