John Hopkins Study Shows That HIV Patients With Moderately Low CD4 Cell Counts Risk Severe Breakthrough COVID-19 Infection

A new study led by researchers from Johns Hopkins Bloomberg School of Public Health has found that HIV patients with moderately low CD4 cell counts risk severe breakthrough COVID-19 infections.


 
The study team said that understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among individuals with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations.
 
The study was aimed at estimating the rate and risk of severe breakthrough illness among vaccinated PWH and individuals without HIV (PWoH) who experience a breakthrough infection.
 
In the cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible.
 
The primary outcome of the study was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status.
 
The study findings showed that 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, −0.67%; 95% CI, −2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/μL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status.
 
The study findings showed that the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.
 
The study findings were published in the peer reviewed journal: JAMA Network Open.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797255
 
The study team also included researchers from University of Calgary-Canada, Mid-Atlantic Permanente Research Institute, Maryland-USA, Stanford Center for Population Health Sciences, California-USA , Connecticut Healthcare System-USA, Yale School of Public Health, Connecticut-USA, University of North Carolin a at Chapel Hill-USA, Kaiser Permanente Northern California-USA, Oakland Medical Center-California, Emory University School of Medicine-USA, School of Public Health, Georgia-USA, Atlanta Veterans Affairs Medical Center, Georgia-USA and the National Institute of Allergy and Infectious Diseases-USA.
 
The study findings suggest that this group should be considered for additional vaccine dosages and other risk-reduction measures.
 
The study team analyzed data from the electronic health records of individuals with and without HIV. Of these, 3,649 individuals had breakthrough COVID-19 infection in the second half of 2021.
 
The study team found that individuals 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.
 
At present, the U.S.CDC recommends individuals who are moderately or severely immunocompromised take additional precautions to protect themselves from COVID-19, including additional doses of vaccine.
 
Senior author Dr Keri Althoff, Ph.D., MPH, associate professor in the Department of Epidemiology at the Bloomberg School told Thailand Medical News, "Individuals with HIV and CD4 counts between 200 and 350 cells/mm3 are not included in the current CDC recommendations. Our findings suggest individuals 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 U.S. Centers for Disease Control and Prevention recommends additional vaccine dosing and regular vaccine boosters for individuals 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 research 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 ie individuals 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.
 
A previous study 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.
 
This new study however looked at the 249 cases of breakthrough infection that were classified as severe because they required hospitalization within 28 days of COVID-19 diagnosis.
 
The study findings showed that, while the risk of severe illness in the first 28 days was low and comparable between individuals 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.
 
It was also noted that among individuals with severe breakthrough infections, 9.6 percent were mechanically ventilated ie 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 ie 7.5 percent in individuals with HIV and 8.2 percent in people without HIV with no difference by HIV status.
 
Dr Althoff added, "Clinicians who care for individuals 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.”
 
First author, Dr 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 Dr Althoff.
 
The study team stressed that among vaccinated individuals 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 study team suggest that the U.S.CDC should consider broadening its recommendations for extra vaccine dosing to include individuals with HIV whose CD4 counts are below 350 cells/mm3.
 
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