COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina.

BACKGROUND: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19. OBJECTIVES: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system. METHODS: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods. RESULTS: Among 44 671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28 days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28 day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%-0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%-0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03-0.26); the fully adjusted HR was 0.16 (95% CI: 0.05-0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area. CONCLUSIONS: COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials.

Analysis of Postvaccination Breakthrough COVID-19 Infections Among Adults With HIV in the United States.

Importance: Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines. Objective: To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States. Design, Setting, and Participants: This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record-based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021. Exposures: HIV infection. Main Outcomes and Measures: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated. Results: Among 113 994 patients (33 029 PWH and 80 965 PWoH), most were 55 years or older (80 017 [70%]) and male (104 967 [92%]); 47 098 (41%) were non-Hispanic Black, and 43 218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rank P < .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (<45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH. Conclusions and Relevance: In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.

Analysis of Severe Illness After Postvaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US.

Importance: 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. Objective: 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. Exposures: HIV infection. 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. Results: 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.

COVID-19 infections post-vaccination by HIV status in the United States.

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.