Analysis of severe illness after post-vaccination COVID-19 breakthrough among adults with and without HIV in the United States
Authors: Lang Raynell , Humes Elizabeth , Coburn Sally B. , Horberg Michael A. , Fathi Lily F , Watson Eric , Jefferson Celeena R , Park Lesley S. , Justice Amy C. , Gordon Kirsha S. , Akgün Kathleen M , Napravnik Sonia , Edwards Jessie K. , Browne Lindsay E. , Agil Deana M. , Silverberg Michael J. , Skarbinski Jacek , Leyden Wendy A. , Stewart Cameron , Hogan Brenna C , Gebo Kelly A. , Marconi Vincent C. , Williams Carolyn F. , Althoff Keri N. ,   the Corona-Infectious-Virus Epidemiology Team (CIVETs) of the NA-ACCORD of IeDEA
Published: April 2022

ABSTRACTImportanceUnderstanding the severity of post-vaccination COVID-19 breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.ObjectiveEstimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection.Design, setting, and participantsThe Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration consists of four US longitudinal cohorts from integrated health systems and academic centers. Adults (≥18 years old), in-care, fully vaccinated by June 30, 2021 with HIV, and matched PWoH (on date fully vaccinated, age group, race/ethnicity, and sex) were the source population. Those who experienced a post-vaccination SARS-CoV-2 breakthrough infection were eligible. Severe COVID-19 breakthrough illness was defined as hospitalization due to COVID-19. Discrete time proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals ([,]) of severe breakthrough illness by HIV status adjusting for demographics, COVID-19 vaccine type, and clinical factors. The proportion of patients requiring mechanical ventilation or died was compared by HIV status.ExposureHIV infectionOutcomeSevere COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis.ResultsAmong 1,241 PWH and 2,408 PWoH with breakthrough infections, the cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs. 6.7%, respectively, risk difference=-0.67% [-2.58%, 1.23%]). The risk of severe breakthrough illness was 59% higher in PWH with CD4 counts <350 cells/mm3 compared with PWoH (aHR=1.59 [0.99, 2.46]). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 count increased the risk of severe breakthrough illness, while previous COVID-19 reduced the risk. Among all patients, 10% were mechanically ventilated and 8% died, with no difference by HIV status.Conclusions and RelevanceThe risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. However, PWH with moderate and severe immune suppression had a higher risk of severe breakthrough infection. Recommendations for additional vaccine doses and risk-reduction strategies for PWH with moderate immune suppression may be warranted.Key PointsQuestionIn 2021, among fully vaccinated people with COVID-19 breakthrough illness, was the risk of severe illness higher in people with HIV (PWH) compared to people without HIV (PWoH)?FindingsPWH with <350 cells/mm3 have a 59% increased risk of severe breakthrough illness compared to PWoH.MeaningVaccinations effectively reduce the risk of severe COVID-19 infection in both PWH and PWoH; however, PWH having a CD4 count <350 cells/mm3 are at higher risk of severe breakthrough infection compared to PWoH. PWH with moderate immune suppression should be considered for additional vaccine dosages and other risk-reduction measures.