Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study

Abstract

Background Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. Methods We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). Results Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). Conclusions HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

“…These multi-morbidities are driven by residual inflammation on ART and ongoing immune dysregulation (Deeks and Phillips 2009) that could influence COVID-19 disease severity, the durability of protective antiviral responses, which may prevent future re-infection, and responsiveness to vaccination (Moir and Fauci 2017; Pallikkuth et al 2012). Although there is no evidence of increased rates of COVID-19 disease among PLWH compared to the general population, mortality estimates vary between studies, with disparities in social health determinants and comorbidities likely having an influence (Bhaskaran et al 2021; Blanco et al 2020; Boulle et al 2020; Cooper et al 2020; Geretti et al 2020; Inciarte et al 2020; Sigel et al 2020). More recently, cellular immune deficiency and a lower CD4 T cell count/low CD4 T cell nadir have been identified as potential risk factors for severe SARS-CoV-2 infection in PLWH, irrespective of HIV virological suppression (Hoffmann et al 2020).…”

COVID-19 death in people with HIV: interpret cautiously

“…An analysis of people hospitalised with COVID-19 in the UK (ISARIC) 3 also found a higher risk of mortality among people with HIV, albeit to a lesser degree, with an adjusted hazard ratio of 1·69 (95% CI 1·15–2·48; p=0·008). Neither study was able to fully adjust for confounders, and Bhaskaran and colleagues excluded people with missing age, sex, or index of multiple deprivation.…”

“…A study from the Western Cape, South Africa, 7 found an association, but data were not complete, because many participants had no recent viral load or CD4 count. Similar to ISARIC, 3 the analysis of OpenSAFELY could not adjust for HIV treatment or surrogate markers of HIV control, which is a major limitation.…”

In depth analysis of patients with severe SARS-CoV-2 in sub-Saharan Africa demonstrates distinct clinical and immunological profiles

“…Due to the high HIV prevalence in our setting, we were able to explore the impact of HIV co-infection on COVID-19. While data from the United Kingdom and South Africa suggests an increased risk of mortality in HIV-infected COVID-19 patients (42-44), a systematic review and data from the United States did not demonstrate this association (45-47). In our cohort, we did not find statistically significant differences in the cytokine responses, prevalence of respiratory pathogens nor mortality between HIV-infected and HIV-uninfected COVID-19 participants.…”