In 2021, among fully vaccinated people with breakthrough COVID-19 illness, was the risk of severe illness higher for people with HIV (PWH) compared with people without HIV (PWoH)?
In this cohort study of 3649 patients with breakthrough COVID-19, there was no overall difference in risk of severe disease between PWH and PWoH. PWH with CD4 cell count less than 350 cells/μL had a 59% increased risk of severe breakthrough illness compared with PWoH.
Although vaccinations effectively reduce the risk of severe COVID-19 illness in both PWH and PWoH, these findings suggest that PWH with moderate or severe immune suppression (CD4 cell count <350 cells/μL) could be at higher risk of severe breakthrough infection compared with PWoH, and PWH with moderate immune suppression should be considered for additional vaccine dosages and other risk-reduction measures.
Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.
To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection.
Design, Setting, and Participants
In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible.
Main Outcomes and Measures
The main outcome was severe 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. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status.
Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, −0.67%; 95% CI, −2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status.
Conclusions and Relevance
In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: August 24, 2022.
Published: October 13, 2022. doi:10.1001/jamanetworkopen.2022.36397
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Lang R et al. JAMA Network Open.
Corresponding Author: Keri N. Althoff, PhD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Rm E7142, Baltimore, MD 20295 (firstname.lastname@example.org).
Author Contributions: Ms Humes and Dr Althoff had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Lang, Fathi, Park, Justice, Napravnik, Marconi, Williams, Althoff.
Acquisition, analysis, or interpretation of data: Lang, Humes, Coburn, Horberg, Watson, Jefferson, Park, Gordon, Akgün, Justice, Napravnik, Edwards, Browne, Agil, Silverberg, Skarbinski, Leyden, Stewart, Hogan, Gebo, Marconi, Althoff.
Drafting of the manuscript: Lang, Coburn, Horberg, Fathi, Marconi.
Critical revision of the manuscript for important intellectual content: Lang, Humes, Coburn, Horberg, Watson, Jefferson, Park, Gordon, Akgün, Justice, Napravnik, Edwards, Browne, Agil, Silverberg, Skarbinski, Leyden, Stewart, Hogan, Gebo, Marconi, Williams, Althoff.
Statistical analysis: Lang, Humes, Coburn, Justice, Napravnik, Edwards, Leyden, Althoff.
Obtained funding: Justice, Napravnik, Althoff.
Administrative, technical, or material support: Fathi, Park, Gordon, Akgün, Justice, Napravnik, Edwards, Browne, Agil, Skarbinski, Leyden, Stewart, Hogan, Gebo.
Supervision: Justice, Napravnik, Marconi, Williams, Althoff.
Conflict of Interest Disclosures: Dr Lang reported receiving grants from Canadian Institutes of Health Research (CIHR), Alberta Innovates, and the University of Calgary paid to their institution. Dr Horberg reported receiving grants from the National Institutes of Health (NIH) paid to their institution. Ms Jefferson reported receiving grants from the NIH paid to their institution. Dr Park reported receiving grants from the NIH paid to their institution. Dr Napravnik reported receiving grants from the NIH paid to their institution. Dr Edwards reported receiving grants from the NIH paid to their institution. Ms Browne reported receiving grants from the NIH paid to their institution. Dr Skarbinski reported receiving grants from the NIH paid to their institution. Dr Gebo reported receiving grants from the NIH and Department of Defense paid to their institution. Dr Marconi has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. Dr Althoff reported receiving grants from the NIH paid to their institution and serving as a consultant to the All of Us Research Program (NIH), TrioHealth, Kennedy Dundas, and MedIQ (fees paid to her). No other disclosures were reported.
Funding/Support: This project was made possible with supplemental funds to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD, U01AI069918) from the National Institute of Allergy and Infectious Diseases (NIAID). The NA-ACCORD is supported by NIH grants U01AI069918, F31AI124794, F31DA037788, G12MD007583, K01AI093197, K01AI131895, K23EY013707, K24AI065298, K24AI118591, K24DA000432, KL2TR000421, N01CP01004, N02CP055504, N02CP91027, P30AI027757, P30AI027763, P30AI027767, P30AI036219, P30AI050409, P30AI050410, P30AI094189, P30AI110527, P30MH62246, R01AA016893, R01DA011602, R01DA012568, R01AG053100, R24AI067039, R34DA045592, U01AA013566, U01AA020790, U01AI038855, U01AI038858, U01AI068634, U01AI068636, U01AI069432, U01AI069434, U01DA036297, U01DA036935, U10EY008057, U10EY008052, U10EY008067, U01HL146192, U01HL146193, U01HL146194, U01HL146201, U01HL146202, U01HL146203, U01HL146204, U01HL146205, U01HL146208, U01HL146240, U01HL146241, U01HL146242, U01HL146245, U01HL146333, U24AA020794, U54GM133807, UL1RR024131, UL1TR000004, UL1TR000083, UL1TR002378, UL1TR002489, Z01CP010214 and Z01CP010176; contracts CDC-200-2006-18797 and CDC-200-2015-63931 from the Centers for Disease Control and Prevention (CDC); contract 90047713 from the Agency for Healthcare Research and Quality; contract 90051652 from the Health Resources and Services Administration; the Grady Health System; grants CBR-86906, CBR-94036, HCP-97105, and TGF-96118 from the CIHR; Ontario Ministry of Health and Long Term Care; and the Government of Alberta, Canada. Additional support was provided by the NIAID, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Human Genome Research Institute, National Institute for Mental Health, National Institute on Drug Abuse, National Institute on Aging, National Institute of Dental & Craniofacial Research, National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research, National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, and National Institute of Diabetes and Digestive and Kidney Diseases.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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