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 findings were published in the peer reviewed journal: JAMA Network Open.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797255

Prior CIVETs collaboration analyses4 showed a 28% increase in breakthrough COVID-19 among PWH vs people without HIV (PWoH). The findings of this cohort study showed that the risk of severe illness (requiring hospitalization) after COVID-19 breakthrough was low (6.8% of 3649 vaccinated PWH and PWoH) and did not differ by HIV status overall.

People with HIV (PWH) with lower CD4 cell counts (<350 cells/μL), however, had higher risk of severe COVID-19 breakthrough illness compared with PWoH, suggesting a role of immune dysfunction in the increased risk.

The lack of difference in severe COVID-19 breakthrough illness risk between PWoH and PWH with higher CD4 cell counts may be associated with engagement in medical care, different health care–seeking behaviors, and reduced comorbidities among the PWH included compared with PWoH.

The increased risk of severe COVID-19 breakthrough illness for PWH with moderate immune suppression (ie, CD4 cell count 200-349 cells/μL)27

(1) suggests that the recommendation for additional primary series vaccination doses should be expanded to PWH with moderate immune suppression,

(2) supports the current recommendation of a first booster, and (3) suggests counseling on risk-reduction strategies among those with moderate immune suppression.

Prior studies28,29 have also demonstrated that greater immune dysfunction is associated with increased severe COVID-19 illness risk in PWH. Both CD4+ and CD8+ T cells have important roles in the viral immune response and are positively correlated with the antibody response to SARS-CoV-2.29,30 CD4+ T-cell function is needed for effective vaccine responses.27,31

The increased risk of severe COVID-19 breakthrough among PWH with lower CD4 cell counts is likely multifactorial and requires further investigation.

Sex, age, comorbidities, additional vaccine doses, and prior COVID-19 infection are associated with the risk of severe COVID-19 breakthrough illness.10,32-34 Among both PWoH and PWH, increasing age was the most significant factor associated with severe COVID-19 breakthrough illness in our study. Female PWoH had reduced risk, which has been previously documented 35-37; however, female PWH had increased risk of severe illness.

It is known that male and female individuals have distinct immune system responses, with female individuals often demonstrating increased immune competence and less inflammatory immune responses, possibly contributing to their reduced risk of severe COVID-19 breakthrough illness; however, immune dysfunction with HIV may alter this effect.35,38,39

Additionally, among the female PWH, a high proportion had obesity, which likely influenced the increased risk of severe breakthrough illness and warrants further investigation.

Despite recommendations for additional COVID-19 vaccine doses being based in part on CD4 cell count,22 we identified that the proportion of PWH who received additional doses was low, varied little by CD4 cell count, and was likely associated with clinical decision-making and patient preference.

Prior COVID-19 has been found to reduce the risk of subsequent COVID-19 illness, particularly following vaccination40; our findings furthered this demonstrating a reduction in severe breakthrough COVID-19 among people with COVID-19 prior to full vaccination.

Among PWoH, several comorbidities have been associated with increased severe COVID-19 breakthrough illness risk.33,34,41 Our findings suggest an increased risk associated with hypertension, ESKD, and SOT. Comorbidities were prevalent among those who experienced a severe COVID-19 breakthrough illness with most having a diagnosis of obesity, diabetes, hypertension, or ESKD.

A lower proportion of PWH had at least 1 comorbidity than PWoH (94.1% vs 82.3%), yet their severe COVID-19 breakthrough rates remained the same as PWoH. In unadjusted analyses, moderate to severe immune suppression from HIV itself was associated with increased risk of severe COVID-19 breakthrough, as were comorbidities and a recent cancer diagnosis among PWH.

Mechanical ventilation and death were rare among both PWH and PWoH with breakthrough COVID-19 and were more likely to be experienced by those older than 55 years with 1 or more comorbidity, highlighting the need for targeted risk reduction measures among older and comorbid adults.