COVID-19 Breakthrough Infection Risk High in Immunosuppressed Patients With HIV – Infectious Disease Advisor

Although the risk for COVID-19 breakthrough infection in vaccinated individuals is low among both those with and without HIV infection, the risk is increased in HIV-positive individuals with moderate to severe immunosuppression. These study findings were published in JAMA Network Open.

Researchers conducted a cohort study to analyze both the rate and risk for severe COVID-19 breakthrough infection among vaccinated adults with vs without HIV infection. Included patients were receiving HIV care and developed COVID-19 breakthrough infection before December 31, 2021; all patients had been vaccinated against COVID-19 infection by June 30, 2021. Patients with vs without HIV infection were matched by date of COVID-19 vaccination receipt, age group, race/ethnicity, and sex.

The primary outcome was severe COVID-19 breakthrough infection, defined as hospitalization within 28 days following breakthrough infection occurrence with a primary or secondary discharge diagnosis of COVID-19. The number of patients who required mechanical ventilation or died was compared by HIV status.

A total of 3649 patients with breakthrough infection were included in the final analysis, of whom 1241 were positive and 2408 were negative for HIV infection. Among all patients, the majority (59.8%) were aged 55 years and older, most (88.9%) were men, and 46.8% were non-Hispanic Black. Of patients with HIV infection, 26.2% had a history of AIDS, 90.6% were virologically suppressed, and the median CD4+ count was 620 (IQR, 438-846) cells/µL.

Severe COVID-19 breakthrough infection and subsequent hospitalization occurred among 79 (6.4%) HIV-positive patients and 170 (7.1%) HIV-negative patients, with a median hospitalization length of 5 (IQR, 3-8) and 4 (IQR, 2-8) days, respectively. There were 12 (0.9%) and 21 (0.8%) deaths within 30 days of diagnosis among patients with and without HIV infection, respectively.

The cumulative 28-day incidence of severe breakthrough infection was similar between patients with (6.7%; 95% CI, 5.2%-8.1%) vs without (7.3%; 95% CI, 6.3%-8.4%) infection (log-rank P =.39). For both HIV-positive and HIV-negative patients, receipt of a COVID-19 booster dose was associated with a decreased risk for severe breakthrough infection.

Discrete time-proportional hazards models were used to estimate breakthrough infection risk by HIV status, with adjustments for demographic characteristics, COVID-19 vaccine type, and clinical factors. Results showed no difference in breakthrough infection risk between patients with vs without HIV infection (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.76-1.35). Compared with HIV-negative patients, HIV-positive patients with CD4+ counts of less than 350 cells/µL had a significantly increased risk for severe breakthrough infection (aHR, 1.59; 95% CI, 0.99-2.46; P =.049).

The potentially increased risk of severe COVID-19 breakthrough illness in PWH with moderate and severe immune suppression merits ongoing surveillance.

Factors associated with an increased risk for severe breakthrough infection among HIV-positive patients included female sex, advanced age, a history of cancer, and decreased CD4+ cell counts. Of note, incident COVID-19 infection prior to vaccination receipt was associated with a decreased risk for breakthrough infection among all patients.

Study limitations include potentially limited generalizability to all HIV-positive populations as well as other SARS-CoV-2 variants.

“The potentially increased risk of severe COVID-19 breakthrough illness in PWH [patients with HIV infection] with moderate and severe immune suppression merits ongoing surveillance,” the researchers concluded.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Lang R, Humes E, Coburn SB, et al. Analysis of severe illness after postvaccination COVID-19 breakthrough among adults with and without HIV in the US. JAMA Netw Open. 2022;5(10):e2236397. doi:10.1001/jamanetworkopen.2022.36397