Outcomes of COVID-19 related hospitalisation among people with HIV in the ISARIC WHO Clinical Characterisation Protocol UK Protocol: prospective observational study
Authors: Geretti Anna Maria , Stockdale Alexander J. , Kelly Sophie H. , Cevik Muge , Collins Simon , Waters Laura , Villa Giovanni , Docherty Annemarie , Harrison Ewen M , Turtle Lance , Openshaw Peter JM , Baillie J Kenneth , Sabin Caroline A. , Semple Malcolm G , Bradshaw Daniel , Brown Alison , Connor Nicky , Delpech Valerie , Khoo Saye , Mbisa Tamyo , Orkin Chloe , Sullivan Ann ,   ISARIC4C Investigators [Listed separately]
Published: August 2020

Background.

There is conflicting evidence about how HIV infection influences COVID-19. We compared the presentation characteristics and outcomes of people with and without HIV hospitalised with COVID-19 at 207 centres across the United Kingdom.

Methods.

We analysed data from people with laboratory confirmed or highly likely COVID-19 enrolled into the ISARIC CCP-UK study. The primary endpoint was day-28 mortality after presentation. We used Kaplan-Meier methods and Cox regression to describe the association with HIV status after adjustment for sex, ethnicity, age, indeterminate/probable hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, and presence/absence of ten comorbidities. We additionally adjusted for disease severity at presentation as defined by hypoxia/oxygen therapy.

Findings.

Among 47,539 patients, 115 (0·24%) had confirmed HIV-positive status and 103/115 (89·6%) had a record of antiretroviral therapy. At presentation, relative to the HIV-negative group, HIV-positive people were younger (median 55 versus 74 years; p<0·001), had a higher prevalence of obesity and moderate/severe liver disease, higher lymphocyte counts and C-reactive protein, and more systemic symptoms. The cumulative incidence of day-28 mortality was 25·2% in the HIV-positive group versus 32·1% in the HIV-negative group (p=0·12); however, stratification for age revealed a higher mortality among HIV-positive people aged below 60 years. The effect of HIV-positive status was confirmed in adjusted analyses (adjusted hazard ratio [HR] 1·49, 95% confidence interval [CI] 0·99-2·25; p=0·06). Following additional adjustment for disease severity at presentation, mortality was higher in HIV-positive people (adjusted HR 1·63; 95% CI 1·07-2·48; p=0·02). In the HIV-positive group, mortality was more common among those who were slightly older and among people with obesity and diabetes with complications.

Interpretation.

HIV-positive status may be associated with an increased risk of day-28 mortality following a COVID-19 related hospitalisation.

Funding.

NIHR, MRC, Wellcome Trust, Department for International Development, Bill and Melinda Gates Foundation.

Study registration

ISRCTN66726260

RESEARCH IN CONTEXT

Evidence before this study

We searched PubMed for articles in all languages containing the words “COVID*”, “coronavirus”, “SARS CoV-2” AND “HIV”. After screening on 23rd July 2020, we found 51 articles reporting outcomes of COVID-19 in HIV-positive people. Of these, 2 were systematic reviews, 24 were single case reports or case series of under 10 participants, and 12 were larger case series or retrospective cohorts without matched controls. There were two cohort studies that matched HIV-positive people diagnosed with COVID-19 to the general population attending for HIV care in the same area, and three studies that matched HIV-positive people diagnosed with COVID-19 to HIV-negative controls. Some of the evidence from the United States and Europe to date suggests that people with HIV experience a similar disease course and outcomes of COVID-19 compared to the general population. However, many of the studies are limited by small sample size, lack of comparator group and lack of adjustment for potential confounding. In contrast, preliminary results from a cohort study of over 20,000 participants in South Africa indicate that HIV-positive status more than doubles the risk of COVID-19 related mortality. Currently, the evidence from the United Kingdom is limited to two case series comprising a total of 21 patients.

Added value of this study

This study analysed data collected from 207 sites across the United Kingdom as part of ISARIC CCP, the largest prospective cohort of patients hospitalised with COVID-19, to evaluate the association between HIV-positive status and day-28 mortality. The study has the benefit of a relatively large number of participants with HIV (n=115, almost all receiving antiretroviral therapy) and importantly, the ability to direct compare their presenting characteristics and outcomes to those of 47,424 HIV-negative controls within the same dataset. This includes the ability to assess the influence of gender, ethnicity and age, as well as the effect of key comorbidities including chronic cardiac, pulmonary, renal and haematological disease, diabetes, obesity, chronic neurological disorder, dementia, liver disease, and malignancy. Unlike some of the other evidence to date, but in line with the data from South Africa, this study indicates that HIV-positive status may increase the risk of mortality with COVID-19 compared to the general population, with an effect that was especially evident among people with HIV aged below 60 years and was independent of gender or ethnicity. Although we detected an association between mortality among people with HIV and occurrence of obesity and diabetes with complication, the effect of HIV-positive status persisted after adjusting for comorbidities.

Implications of all the available evidence

People with HIV may be at increased risk of severe outcomes from COVID-19 compared to the general population. Ongoing data collection is needed to confirm this association. Linkage of hospital outcome data to the HIV history will be paramount to establishing the determinants of the increased risk. COVID-19 related hospitalisation should pursue systematic recording of HIV status to ensure optimal management and gathering of evidence.