People with HIV (PWH) have an increased risk for breakthrough SARS-CoV-2 infection after vaccination, according to a study published in JAMA Network Open. Keri N. Althoff, PhD, MPH, and colleagues estimated the rate of and risk for breakthrough infections among fully vaccinated PWH (N=33,029) and people without HIV (PWoH; 80,965) in the United States. PWH had a higher rate of breakthrough infections than PWoH (55 vs 43 cases per 1,000 person years). At 9 months after full vaccination, the cumulative incidence of breakthrough infections was low (3.8%) but was higher in PWH than PWoH (4.4% vs 3.5%). The risk for breakthrough infection was higher in PWH than PWoH (adjusted HR, 1.28). An increased risk for breakthrough infection among PWH was seen in association with younger age (<45 vs 45-54), history of COVID-19, and not receiving an additional dose (adjusted HR, 0.71). Breakthrough infection was not associated with HIV viral load suppression, but among PWH, a high CD4 count was associated with fewer breakthrough infections.