COVID-19 Breakthrough Infection Risk Increased in Vaccinated Adults With HIV

Illustration of Human Immunodeficiency Virus (HIV) in blood. HIV is a RNA virus from the Retroviridae family that causes acquired immune deficiency syndrome (AIDS).
Investigators assessed the risk for COVID-19 breakthrough infections among vaccinated adults with HIV infection.

Adults with HIV infection who were vaccinated against COVID-19 infection were at an increased risk for a breakthrough infection, suggesting additional COVID-19 booster doses may benefit this patient population. These findings were published in JAMA Network Open.

Investigators accessed 4 prospective, electronic health record-based cohorts from integrated health care systems and academic health centers to assess data captured from fully-vaccinated adults with HIV infection. Patients with HIV infection were matched against 2 to 3 fully-vaccinated adults without HIV infection, with adjustments made on the basis of age, race/ethnicity, sex, and date of vaccination. Eligible patients were those who were fully vaccinated against COVID-19 infection before June 30, 2021; Patients were observed through December 31, 2021. The main outcome was the incidence of COVID-19 breakthrough infections. Incidence rates (IRs) were calculated per 1000 person-years (py) for each month, by HIV status, and by type of COVID-19 vaccine. Cox proportional hazards regression models were used to assess unadjusted and adjusted hazard ratios (HR). Investigators also assessed CD4 count and HIV viral load as potential risk factors for a breakthrough infection.

There were 113,994 patients included in the study, of whom 33,029 were positive for HIV infection and 80,965 were negative for HIV infection. Among all patients, most were aged 55 years and older (70%), men (92%), and nonHispanic Black (41%).

The investigators found that the rate of breakthrough infections was increased among patients with (IR, 55 per 1000 py; 95% CI, 52-58) vs those without (IR, 43 per 1000 py; 95% CI, 42-45) HIV infection. Although the cumulative incidence of breakthrough infections at 9 months was low (3.8%; 95% CI, 3.7-3.9), it was significantly increased among patients with vs without HIV infection (4.4% vs 3.5%; log-rank P <.001). Overall, the incidence of breakthrough infections was most increased among patients who received the Ad26.COV2.S vaccine (IR, 70 per 1000 py; 95% CI, 63-78).

In the adjusted analysis, the investigators observed a significantly increased risk for breakthrough infections among patients with vs without HIV infection (aHR, 1.28; 95% CI, 1.19-1.37). This increased risk for breakthrough infections in HIV-positive patients also was observed after the exclusion of those previously infected with COVID-19 (aHR, 1.30; 95% CI, 1.20-1.40). Among HIV-positive patients, receipt of the mRNA-1273 vaccine was associated with a decreased breakthrough infection risk compared with receipt of the BNT162b2 vaccine (aHR, 0.66; 95% CI, 0.57-0.77). Receipt of the mRNA-1273 vaccine plus an additional booster dose of any type of vaccine also was associated with a decreased breakthrough infection risk (aHR, 0.50; 95% CI, 0.38-0.67), as well as receipt of a BNT162b2 vaccine booster (aHR, 0.71; 95% CI, 0.58-0.88).

No associations were observed between breakthrough infection risk and HIV viral load suppression, but an increased CD4 count (>500 cells/mm3) was associated with a decreased risk for a breakthrough infection.

This study was limited by the inability to account for comorbidities among HIV-positive patients, as those with comorbidities may have been at a decreased risk for a breakthrough infection due to an increased likelihood to receive additional vaccine doses and more frequent COVID-19 testing. These findings also may not be generalizable to all US adults with HIV infection as the patient population comprised mostly men and those with regular access to health care.

According to the investigators, “[an] increased risk [for] breakthrough infections in [patients with HIV infection] merits continued monitoring as the pandemic persists, immunity to primary vaccine series wanes, boosters are widely recommended, and new [COVID-19] variants emerge.”


Coburn SB, Humes E, Lang R, et al. Analysis of postvaccination breakthrough COVID-19 infections among adults with HIV in the United States. JAMA Netw Open. Published online June 1, 2022. doi:10.1001/jamanetworkopen.2022.15934