Abstract
IMPORTANCE: Recommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. OBJECTIVE: Estimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. DESIGN SETTING AND PARTICIPANTS: The Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals ≥18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. EXPOSURE: HIV infection. OUTCOME: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. RESULTS: Among 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. CONCLUSIONS AND RELEVANCE: COVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.