A collision of pandemics: HIV and COVID-19

From the beginning of the pandemic, serious concerns were raised that COVID-19 might be associated with more severe disease and worse outcomes in people living with HIV. These concerns were not unfounded, given that respiratory viral infections are common, and might be more severe, in people living with HIV. Influenza, for example, leads to mortality rates up to 20-times greater in people with HIV, compared with those without HIV.¹ Data regarding the outcomes of COVID-19 in people living with HIV have been conflicting. Initial matched case-control studies from the UK,² USA,³ and South Africa⁴ showed no difference in disease severity and outcomes, including need for intensive care unit admission and death, compared with people who were HIV-negative, especially when adjusting for potential confounding demographic, clinical, and laboratory parameters.3, 4 In contrast, large-scale population-based data from South Africa have shown an association between COVID-19 mortality and HIV status.5, 6

Subsequent systematic and scoping reviews have also yielded conflicting data. An early review of 36 studies, including more than 89 000 patients, concluded that people living with HIV have a lower risk for severe COVID-19, especially in the setting of advanced HIV disease with low CD4 cell counts, although the authors acknowledged that there were contradictory findings in the different studies included in the review.⁷ A more recent scoping review of 20 studies noted an increased risk of COVID-19 mortality in people living with HIV.⁸ While yet another meta-analysis, including 44 studies reporting on more than 38 million patients with COVID-19, found that people living with HIV are at increased risk of COVID-19-related hospitalisation, but not death.⁹

In The Lancet HIV, Sylvia Bertagnolio and colleagues¹⁰ report the findings of a study undertaken to assess whether people living with HIV were at greater risk of more severe or critical disease on hospital admission for COVID-19 infection, and whether they had a higher inpatient mortality (primary outcomes) when compared with people who were HIV-negative. They used data from the WHO Global Clinical Platform on COVID-19—a secure, web-based database of anonymised individual-level, clinical data of hospitalised patients with suspected or confirmed COVID-19 infection in different health-care facilities across the world, established in April, 2020, to which data have, and are, being submitted using a standardised case report form and dictionary. In their study, descriptive and regression analyses were used to summarise demographic and clinical characteristics of the patients by HIV status to evaluate the association of HIV with the primary outcome.

The analysis included 197 479 patients (of these, 16 955 [8·6%] were people living with HIV and 180 524 were HIV-negative) submitted to the platform between Jan 1, 2020, and July 1, 2021, from 38 countries. Overall, 94·6% of the people living with HIV were from Africa, mostly from South Africa (16 008/16 955). 38·4% were admitted with severe illness and 24·3% died in hospital. Of the people for whom information was available, 91·5% were receiving antiretroviral therapy (ART). The main outcome findings were that people living with HIV had a 15% greater odds of a severe or critical COVID-19 presentation (aOR 1·15, 95% CI 1·10–1·20) and a 38% greater chance of dying in hospital (aHR 1·38, 1·34–1·41) compared with people who were HIV-negative. Although additional subgroup analyses showed an association between individuals using ART or viral load suppression with a reduced risk of poor outcomes, HIV infection itself still remained a risk factor for severity of illness and mortality. As has been noted previously, the presence of at least one additional underlying comorbidity was more frequent among people living with HIV compared with people who were HIV negative,3, 4, 5 which indicates that not only does HIV need to be comprehensively managed with ART to achieve viral suppression, but also prevention and good management of associated comorbid conditions are essential for better COVID-19 outcomes.

The authors recognise the potential limitations of their study, largely related to missing data—specifically CD4 cell counts, use of ART, viral loads, and vaccination coverage, as well as there being sparse data available on COVID-19 therapeutics, precluding an analysis of their potential impact on outcomes. Fortunately, as the authors indicate, they are intending to analyse data on an ongoing basis as datasets are received from other countries, and are expanding their collection of variables, to include other parameters of interest.

This study adds to the growing body of literature on the potential negative impact of HIV infection on COVID-19 infection. However, given the continued discordance in findings, prospective studies with long-term follow-up are also warranted to assess the true impact of HIV on COVID-19 severity and outcome.

We declare no competing interests.