SARS-CoV-2 live virus neutralization after four COVID-19 doses in people with HIV receiving immunosuppressive antiretroviral therapy

This study examines the immune benefits of receiving a fourth COVID-19 vaccine dose for people with HIV (PWH) who are on suppressive antiretroviral therapy (ART). It focuses on how well their immune systems can neutralize different strains of the SARS-CoV-2 virus after vaccination, especially given that many of these individuals have already had a COVID-19 infection.

A group of 63 PWH (19 individuals who had never been infected with COVID-19 and 44 individuals who had previously been infected with COVID-19) who received a fourth dose of the COVID-19 vaccine were studied. Participants received either monovalent (targeting a single virus strain) or bivalent (targeting multiple strains) mRNA vaccines for their fourth dose.

Fourth doses were received an average of 8.5 months post-third dose, where Pfizer monovalent was given to 14%, Pfizer bivalent was given to 14%, Moderna monovalent was given to 30%, and Moderna bivalent was given to 41% of participants. Overall, 30% of participants remained SARS-CoV-2-naive, with 19% and 51% experiencing COVID-19 during the pre-Omicron and Omicron eras, respectively, and 44% of participants received monovalent and 56% bivalent mRNA fourth doses.

Live virus neutralization was used to measure the ability of the participants’ immune systems to neutralize: Original (wild-type) virus, Omicron BA.5 variant and Omicron BQ.1 variant.

Key findings:

• In those who had never been infected, the fourth dose modestly increased their ability to neutralize both the wild-type virus and the BA.5 variant compared to after three doses.
• In those who had previously been infected, the fourth dose modestly increased neutralization of the wild-type virus and significantly increased neutralization of the BA.5 variant.
• Consistent with the humoral benefits of “hybrid” immunity, PWH that experienced COVID-19 infection exhibited the highest neutralization post-fourth dose overall. In those specifically with Omicron-era infections, higher wild-type specific but similar BA.5 and BQ.1-specific neutralization was observed when compared to those with pre-Omicron-era infections.
• Across all participants, neutralization of the BA.5 variant was consistently lower than the wild-type virus, and neutralization of the BQ.1 variant was even lower still.
• The type of fourth dose (monovalent or bivalent) did not significantly affect the level of neutralization. However, receiving the Moderna vaccine for the fourth dose was associated with stronger neutralization of the wild-type virus, while prior COVID-19 infection was the strongest predictor of higher neutralization for the BA.5 and BQ.1 variants.

Overall, the study concludes that a fourth COVID-19 vaccine dose provides significant immune benefits to PWH, regardless of whether they have had a prior COVID-19 infection. These findings support recommendations for all adults, including those with HIV, to receive a fourth vaccine dose within six months of their third dose or their most recent COVID-19 infection.

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