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Risk of Severe Breakthrough COVID-19 Infection is Higher for People with HIV with Moderately Low CD4 Cell Counts

Finding suggests that people with HIV who have CD4 counts lower than 350 cells per microliter should take extra precautions against COVID-19


People with HIV who have moderate immune suppression appear to be at greater risk of severe COVID-19 “breakthrough” infection after vaccination, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.

These findings suggest that this group should be considered for additional vaccine dosages and other risk-reduction measures.

For the study, researchers analyzed data from the electronic health records of people with and without HIV. Of these, 3,649 people had breakthrough COVID-19 infection in the second half of 2021. The researchers found that people with HIV did not have a significantly higher rate of severe COVID-19 breakthrough infection. Among the group with HIV, the researchers found that those who had CD4 counts lower than 350 cells/cubic millimeter of blood, were 59 percent more likely to have severe breakthrough infections compared to people without HIV.

The study was published online October 13 in JAMA Network Open.

Currently, the CDC recommends people who are moderately or severely immunocompromised take additional precautions to protect themselves from COVID-19, including additional doses of vaccine.

“People with HIV and CD4 counts between 200 and 350 cells/mm3 are not included in the current CDC recommendations,” says study senior author Keri Althoff, PhD, MPH, associate professor in the Department of Epidemiology at the Bloomberg School. “Our findings suggest people with HIV who have CD4 counts less than 350 cells/mm3 should be considered moderately or severely immunocompromised by the CDC, and encouraged to take additional precautions to protect themselves from severe COVID-19.”

 The Centers for Disease Control and Prevention recommends additional vaccine dosing and regular vaccine boosters for people who are moderately or severely immunocompromised. Although people do not need to prove their immunocompromised status to obtain extra vaccinations per the CDC’s guidelines, this category includes people with advanced or untreated HIV infection, defined as a CD4 T-cell count below 200 cells per microliter and an unsuppressed HIV viral load.

The new study made use of the Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort, which included patients from the health systems of Kaiser Permanente Mid-Atlantic States, Kaiser Permanente Northern California, the Veterans Health Administration, and the University of North Carolina. The initial study population included 33,029 people with HIV, and 80,965 people without HIV, who were fully vaccinated against COVID-19 during the period December 2020 through June 2021. The two groups—people with and without HIV—were matched on demographic factors such as age and sex, and by date of vaccination.

In the CIVET cohort, there were 3,649 cases of post-vaccination COVID-19 breakthrough infection, the vast majority mild, in the two groups combined. In a companion study published in June, Althoff and colleagues showed that these breakthrough infections happened at a higher rate in the HIV group, suggesting a 28 percent greater risk, compared to the non-HIV group. However, the level of absolute risk was low, at just 4.4 percent for the HIV group versus 3.8 percent for the non-HIV group.

In the new study, the researchers looked at the 249 cases of breakthrough infection that were classified as severe because they required hospitalization within 28 days of COVID-19 diagnosis. They found that, while the risk of severe illness in the first 28 days was low and comparable between people with HIV (7.3 percent) and people without HIV (6.7 percent), more immunocompromised people with HIV, with CD4 counts lower than 350 cells/mm3, had a 59 percent higher risk than people without HIV.

Among people with severe breakthrough infections, 9.6 percent were mechanically ventilated—10.1 percent in people with HIV and 9.4 percent in people without HIV—and 8.0 percent died during or within 30 days of hospitalization—7.5 percent in people with HIV and 8.2 percent in people without HIV—with no difference by HIV status.

“Clinicians who care for people with HIV with moderately low CD4 counts, that is with CD4 counts less than 350 cells/mm3, should encourage them to take additional precautions to prevent severe breakthrough COVID-19 illness,” adds Althoff.

The study’s first author, Raynell Lang, MD, MPH, assistant professor in the Department of Medicine at the Cumming School of Medicine, University of Calgary, worked on the study during a postdoctoral fellowship with Althoff.

Among vaccinated people with HIV, being older, being female, or having a cancer diagnosis also was associated with a greater risk of hospitalization, whereas having had COVID-19 previously was associated with lower risk.

The findings, according to Althoff, suggest that the CDC should consider broadening its recommendations for extra vaccine dosing to include people with HIV whose CD4 counts are below 350 cells/mm3.
“Analysis of Severe Illness After Post-Vaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US” was co-authored by Raynell Lang, Elizabeth Humes, Sally Coburn, Michael Horburg, Lily Fathi, Eric Watson, Celeena Jefferson, Lesley Park, Kirsha Gordon, Kathleen Akg
ün, Amy Justice, Sonia Napravnik, Jessie Edwards, Lindsay Browne, Deana Agil, Michael Silverberg, Jacek Scarbinski, Wendy Leyden, Cameron Stewart, Brenna Hogan, Kelly Gebo, Vincent Marconi, Carolyn Williams, and Keri Althoff.

The study was funded as a supplement to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD, U01AI069918) from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

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