Home Immunity Moderately Immunosuppressed HIV-Positive Patients at Increased Risk of Severe ‘Breakthrough’ COVID-19 Infection

Moderately Immunosuppressed HIV-Positive Patients at Increased Risk of Severe ‘Breakthrough’ COVID-19 Infection


According to a study by researchers at the Johns Hopkins Bloomberg School of Public Health, people living with HIV who have moderate immunosuppression appear to be at higher risk of severe COVID-19 infection after vaccination.

These results suggest that this group should be considered for additional vaccine doses and other risk reduction measures.

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

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

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

People living with HIV and CD4 count between 200 and 350 cells/mm3 are not included in current CDC recommendations. Our results suggest that people living with HIV who have CD4 counts below 350 cells/mm3 should be considered moderately or severely immunocompromised by the CDC, and encouraged to take extra precautions to protect against severe COVID-19. »

Keri Althoff, PhD, MPH, Study Senior Author, Associate Professor, Department of Epidemiology, Bloomberg School

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

The new study used the Corona Virus Epidemiology Team (CIVET)-II cohort, which included patients from Kaiser Permanente’s Mid-Atlantic State Health Systems, Kaiser’s Northern California Permanente, the Veterans Health Administration and the University of North Carolina. The initial study population included 33,029 people living with HIV and 80,965 people without HIV, who were fully vaccinated against COVID-19 during the period of December 2020 to June 2021. Both groups – people with and HIV-free – 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 breakthrough COVID-19 infection post-vaccination, the vast majority mild, in the two groups combined. In a complementary study published in June, Althoff and colleagues showed that these breakthrough infections occurred at a higher rate in the HIV group, suggesting a 28% higher risk, compared to the non-HIV group. However, the absolute risk level was low, at only 4.4% for the HIV-positive group versus 3.8% for the non-HIV-positive group.

In the new study, researchers looked at the 249 cases of breakthrough infection that were classified as severe because they required hospitalization within 28 days of being diagnosed with COVID-19. They found that although the risk of serious illness in the first 28 days was low and comparable between HIV-positive (7.3%) and non-HIV-positive people (6.7%), more immunocompromised people with HIV, with a CD4 count below 350 cells/mm3were at 59% higher risk than people without HIV.

Of those with breakthrough severe infections, 9.6% were mechanically ventilated; 10.1% among HIV-positive people and 9.4% among non-HIV-positive people; and 8.0% died during or within 30 days of hospitalization; 7.5% among HIV-positive people and 8.2% percent among non-HIV-positive people; without difference according to serological status.

“Clinicians caring for people living with HIV with moderately low CD4 counts, i.e. CD4 counts below 350 cells/mm3should encourage them to take extra precautions to prevent serious outbreaks of COVID-19,” adds Althoff.

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

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

The results, according to Althoff, suggest the CDC should consider expanding its recommendations for additional vaccine dosing to include people living with HIV whose CD4 count is less than 350 cells/mm.3.

“Analysis of Severe Illness After COVID-19 Post-Vaccination Breakthrough in Adults With and Without HIV in the United States” was co-authored by Raynell Lang, Elizabeth Humes, Sally Coburn, Michael Horburg, Lily Fathi, Eric Watson , Celeena Jefferson, Lesley Park, Kirsha Gordon, Kathleen Akgün, 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 additionally funded by the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD, U01AI069918) of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.


Johns Hopkins University Bloomberg School of Public Health

Journal reference:

Lang, R. et al. (2022) Analysis of severe illness after COVID-19 breakthrough after vaccination in adults with and without HIV in the United States. JAMA network open. doi.org/10.1001/jamanetworkopen.2022.36397.