Patient characteristics and HIV-related factors, particularly CD4 cell count, influence the risk for breakthrough COVID-19 infection following vaccination.


“While patients with more advanced HIV are known to be at greater risk for COVID-19, the question of whether vaccination against COVID-19 would benefit all patients with HIV remained,” Michael A. Horberg, MD, MAS, FACP, FIDSA, explained. “Early data suggested that increased risk exists for patients with HIV (PWH) even if they are vaccinated, but the populations included in those studies weren’t diverse, and we wanted to look specifically at US data.”

Dr. Horberg also noted that previous research did not include a comparison group composed of people without HIV (PWoH). “We felt a better study would help guide policymakers and, potentially, the CDC, as they were initially speaking about using CD4 cell counts to classify PWH as ‘immunocompromised.’”

For a study published in JAMA Network Open, Dr. Horberg and colleagues estimated the rates of, and risk for, severe breakthrough infection among vaccinated PWH and PWoH. The cohort study included PWH who were engaged in care and fully vaccinated and PWoH who were matched based on age, race, ethnicity, sex, and the date they completed the full vaccine series. Eligible patients, or those with a post-vaccination breakthrough COVID-19 infection, were enrolled from four US integrated health systems and academic medical centers. The researchers also compared the proportion of patients who received mechanical ventilation or died according to HIV status.

CD4 Cell Count Tied to Risk for Breakthrough Infection

Regarding the results, Dr. Horberg first noted that “vaccination works.”

“Among 113,994 patients, including 33,029 PWH and 80,965 PWoH, only 249 individual 79 PWH and 170 PWoH experienced severe COVID-19 breakthrough infection and were hospitalized,” he said.

More than half of the individuals who experienced a breakthrough infection were aged 55 and older (59.8%), and most (88.9%) were male. The risk for severe breakthrough infection among patients with HIV was 59% higher in those with CD4 counts below 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99-2.46). In multivariable analyses among PWH, female sex, older age, a cancer diagnosis, and a lower CD4 cell count were associated with greater risk for severe breakthrough illness, while prior infection with COVID-19 was associated with decreased risk.

“Curiously, risk didn’t differ by viral load,” Dr. Horberg noted. “Regardless of vaccine type, receipt of a booster was associated with reduced risk for severe breakthrough infection regardless of HIV status, particularly among PWH with lower CD4 counts (Figure).”

‘Don’t Accept Defeat’ When Discussing COVID-19 Vaccination

The study results demonstrate that, overall, there was no major difference in the rate of severe breakthrough illness according to HIV status, but “this risk is not zero,” even following vaccination, according to Dr. Horberg.

“Ensure that your patients with HIV get vaccinated and boosted against COVID-19,” he said. “Don’t drop the topic if they refuse to do so bring it up every visit. Think about the conversations you have when encouraging patients to quit smoking; don’t accept defeat just because they say ‘no’ once.”

Dr. Horberg also emphasized the role of CD4 cell count. “The lower the CD4 count, the more important the booster becomes,” he said. “Consider outreach to those PWH with lower CD4 counts to get them vaccinated and boosted, and, of course, make sure your patients achieve viral suppression so that their CD4 counts recover to more than 350.”

Regarding future research, Dr. Horberg and colleagues are working “to address the important question” of whether vaccination impacts post-acute sequelae of SARS-CoV-2, or PASC, particularly among PWH compared with PWoH.

“We also need to determine if our conclusions remain for patients who are not getting frequent COVID-19 boosters, based on recommendations from the Advisory Committee on Immunization Practices, and with different variants,” he said.