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Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19
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May 10, 2022
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Three exploratory subgroup analyses were done to assess the impact of geographical region, ART use, and viral load status on mortality and severity. Compared with people who were HIV-negative, people living with HIV were more likely to die from COVID-19 in the WHO African region (aHR 1⋅28, 95% CI 1⋅24-1⋅33), but not in the WHO European region (aHR 1⋅50, 0⋅77-2⋅94) or WHO region of the Americas (aHR 1⋅18, 0⋅76-1⋅82), after adjusting for age, sex, underlying conditions, and clinical presentation.
In an exploratory subgroup analysis assessing the effect of ART on mortality in a subset of 9097 patients from South Africa reporting ART information, both people living with HIV on ART (aHR 1⋅48, 95% CI 1⋅39-1⋅57) and not on ART (aHR 1⋅79, 1⋅48-2⋅16) had a significantly higher risk of death compared with people who were HIV-negative.
A similar exploratory analyses on a sample of 5793 patients from South Africa reporting viral load information (68⋅5% viral load of <1000 copies per mL, 31⋅5% viral load of >1000 copies per mL) showed that the risk of death was equally greater among people living with HIV with viral load of more than 1000 copies per mL (aHR 1⋅77, 1⋅57-1⋅99) and in those with viral load of less than 1000 copies per mL (aHR 1⋅45, 1⋅32-1⋅58) compared with individuals who were HIV-negative.
Finally, risk factors for in-hospital mortality and severity among people living with HIV were then determined. Among people living with HIV the most significant risk factor for in-hospital mortality was severe or critical presentation (aHR 1⋅86, 95% CI 1⋅82-1⋅90), followed by chronic kidney disease, diabetes, malignant neoplasms, tuberculosis, male sex, and hypertension. Increase in age category was associated with increased mortality risk (table 4). Among people living with HIV, factors significantly associated with severe or critical COVID-19 at admission were chronic cardiac disease, male sex, and age 45-75 years (appendix 2 p 10).
Summary
Background
WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors.
Methods
Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors.
Findings
Of 197 479 patients reporting HIV status, 16 955 (8⋅6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62⋅9%) were female and 6271 (37⋅1%) were male; the mean age was 45⋅5 years (SD 13⋅7); 6339 (38⋅3%) were admitted to hospital with severe illness; and 3913 (24⋅3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91⋅5%) were on ART.
Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1⋅15, 95% CI 1⋅10-1⋅20) and were 38% more likely to die in hospital (aHR 1⋅38, 1⋅34-1⋅41).
Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status.
Interpretation
In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available.
Risk factors for in-hospital mortality and severity were determined in the hospitalised population. After adjusting for age, sex, disease severity at admission, and underlying conditions (ie, diabetes, tuberculosis, chronic kidney diseases, pulmonary diseases, and malignancies), patients with HIV were 38% more likely to die than individuals without HIV (aHR 1⋅38, 95% CI 1⋅34-1⋅41). Other significant risk factors independently associated with mortality were male sex, severe or critical presentation, tuberculosis, diabetes, malignant neoplasms, chronic pulmonary disease, and kidney disease (table 3). Increasing age over 18 years showed a gradually and consistently elevated mortality risk.
HIV infection was associated with 15% increased odds of severe or critical presentation (aOR 1⋅15, 95% CI 1⋅10-1⋅20) compared with individuals who were HIV-negative, after adjusting for age, sex, diabetes, tuberculosis, malignant neoplasms, chronic kidney disease, cardiac disease, pulmonary disease, and corticosteroid use. Other factors associated with severe or critical presentation were age older than 45 years (compared with individuals <18 years), chronic cardiac disease, diabetes, and malignancy (appendix 2 p 7). The increased odds of severe or critical disease and risk of mortality in people living with HIV compared with non-HIV were consistent in models adjusting for underlying condition burden (number of underlying conditions, rather than individual conditions; appendix 2 pp 8-9).
Among people with severe presentation, the median time from hospital admission to death was shorter in people living with HIV (19 days, IQR 6-49) compared with HIV-negative individuals (23 days, 10-51; p<0⋅0001). Conversely, among people with mild or moderate presentation, the median time from hospital admission to mortality was longer in people living with HIV (80 days, 14-not estimable) compared with people who were HIV-negative (32 days, 15-102; p<0⋅0026).
38⋅4% of people living with HIV were admitted to the hospital in severe or critical condition and 24⋅3% died (table 1). People living with HIV with severe or critical disease were more likely to be older than 45 years and male (p<0⋅05; appendix 2 p 5), than individuals with mild or moderate presentation at admission. People with severe COVID-19 were also more likely to have diabetes, hypertension, malignancies, cardiac disease, and kidney disease (p<0⋅0001). The frequency of ICU admission and case-fatality rates were significantly higher in the severe or critical group, compared with the milder group (ICU admission 5⋅5% vs 0⋅8%; case-fatality rate 37⋅3% vs 17⋅1%; p<0⋅0001 for both).
Compared with people living with HIV who were discharged alive, individuals who died in hospital were more likely to be older than 45 years and male. Individuals who died in hospital, compared with individuals who were discharged, had significantly higher proportions of diabetes (32⋅9% vs 19⋅4%), hypertension (43⋅8% vs 30⋅1%), tuberculosis (28⋅3% vs 22⋅9%), chronic kidney disease (10⋅1% vs 4⋅1%), and malignancies (2⋅7% vs 1⋅3%; all p<0⋅0001). Having asthma, chronic cardiac, pulmonary and neurological conditions, and current smoking were not significantly different between groups. People living with HIV who died were more likely to be admitted with severe or critical disease than those with mild or moderate disease (p<0⋅0001; table 2).
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