Factors Associated With Severity of COVID-19 Disease in a Multicenter Cohort of People With HIV in the United States, March–December 2020

Adrienne E. Shapiro, MD, PhD; Rachel A. Bender Ignacio, MD, MPH; Bridget M. Whitney, PhD; Joseph A. Delaney, PhD; Robin M. Nance, MS; Laura Bamford, MD, MSCE; Darcy Wooten, MD, MS; Jeanne C. Keruly, MS, CRNP; Greer Burkholder, MD, MSPH; Sonia Napravnik, PhD; Kenneth H. Mayer, MD; Allison R. Webel, RN, PhD; H. Nina Kim, MD, MSc; Stephen E. Van Rompaey, PhD; Katerina Christopoulos, MD, MPH; Jeffrey Jacobson, MD; Maile Karris, MD; Davey Smith, MD, MAS; Mallory O. Johnson, PhD; Amanda Willig, RD, PhD; Joseph J. Eron, MD, MPH; Peter Hunt, MD; Richard D. Moore, MD, MHS; Michael S. Saag, MD; W. Christopher Mathews, MD, MSPH; Heidi M. Crane, MD, MPH; Edward R. Cachay, MD, MAS; Mari M. Kitahata, MD, MPH


J Acquir Immune Defic Syndr. 2022;90(4):369-376. 

In This Article

Abstract and Introduction


Background: Understanding the spectrum of COVID-19 in people with HIV (PWH) is critical to provide clinical guidance and risk reduction strategies.

Setting: Centers for AIDS Research Network of Integrated Clinic System, a US multisite clinical cohort of PWH in care.

Methods: We identified COVID-19 cases and severity (hospitalization, intensive care, and death) in a large, diverse HIV cohort during March 1, 2020–December 31, 2020. We determined predictors and relative risks of hospitalization among PWH with COVID-19, adjusted for disease risk scores.

Results: Of 16,056 PWH in care, 649 were diagnosed with COVID-19 between March and December 2020. Case fatality was 2%; 106 (16.3%) were hospitalized, and 12 died. PWH with current CD4 count <350 cells/mm3 [aRR 2.68; 95% confidence interval (CI): 1.93 to 3.71; P < 0.001] or lowest recorded CD4 count <200 cells/mm3 (aRR 1.67; 95% CI: 1.18 to 2.36; P < 0.005) had greater risks of hospitalization. HIV viral load and antiretroviral therapy status were not associated with hospitalization, although most of the PWH were suppressed (86%). Black PWH were 51% more likely to be hospitalized with COVID-19 compared with other racial/ethnic groups (aRR 1.51; 95% CI: 1.04 to 2.19; P = 0.03). Chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hypertension, obesity, and increased cardiovascular and hepatic fibrosis risk scores were associated with higher hospitalization risk. PWH who were older, not on antiretroviral therapy, and with current CD4 count <350 cells/mm3, diabetes, and chronic kidney disease were overrepresented among PWH who required intubation or died.

Conclusions: PWH with CD4 count <350 cells/mm3, and a history of CD4 count <200 cells/mm3, have a clear excess risk of severe COVID-19, accounting for comorbidities associated with severe outcomes. PWH with these risk factors should be prioritized for COVID-19 vaccination and early treatment and monitored closely for worsening illness.


The COVID-19 pandemic has had profound direct and structural effects on the health of people with HIV (PWH) in the United States.[1] The first observations of COVID-19 in PWH occurred during a period of hospital crowding and rationed testing and treatment.[2–4] A large population-based study from South Africa was the first to indicate a 2-fold higher risk of COVID-19 mortality among PWH[5] but lacked data on comorbid conditions. Subsequent global registry data also showed elevated COVID-19 mortality risk in PWH but had limited ability to examine the contribution of HIV-specific factors and comorbidities to mortality.[6,7]

Understanding risks for poor COVID-19 outcomes is important because PWH are often marginalized and experience health disparities driven partly by social determinants of health that increase the risk of both exposure to COVID-19 and severity of disease.[8] PWH experience a disproportionate burden of medical comorbidities,[9] higher rates of smoking,[10] drug and alcohol use,[11–15] and socioeconomic and racial disparities.[16,17] Not all PWH experience overt immunosuppression, but HIV itself, chronic immune activation and exhaustion, and metabolic complications of HIV and antiretroviral therapy (ART) contribute to non–AIDS-defining morbidity, even in PWH with high CD4 counts and suppressed viral load (VL).[18–20] Understanding the effect of HIV-associated and other factors on COVID-19 disease progression remains important to enable clinicians to provide appropriate risk assessment and prioritize COVID-19 prevention and treatment efforts, especially in settings where such resources remain limited. The objective of this study was to identify predictors of COVID-19 severity, including risk for hospitalization, need for mechanical respiratory support, and death, among PWH with COVID-19 in the United States