The risk of severe COVID-19 and mortality from COVID-19 in people living with HIV compared to individuals without HIV - a systematic review and meta-analysis of 1 268 676 individuals
Abstract
Background
There is conflicting evidence about the risk of mortality and severe disease due to COVID-19 in people living with HIV (PLHIV).
Objectives
To compare mortality, hospitalization, and the need for intensive care services due to COVID-19 between PLHIV and individuals without HIV based on data from the existing literature.
Methods
A comprehensive search in PubMed, Cochrane Library, Scopus, China Academic Journals Full Text Database, the Database of Abstracts of Reviews of Effectiveness (DARE) and and the medRXIV and bioRxiv databases of preprints was carried out. Each data source was searched from 1 January 2020 to 20th of February 2021. Eligible studies were case control, cross-sectional and cohort studies where participants had confirmed COVID-19. From each study, data on numbers of PLHIV and individuals without HIV for each outcome were extracted. Study quality was assessed using the MethodologicAl STandard for Epidemiological Research (MASTER) scale. Data synthesis used a bias adjusted model and predefined age and geographical subgroups were analysed.
Results
Of a total of 2757 records identified, 11 studies, from 4 countries, the United Kingdom, Spain, the United States of America and South Africa, were included. The total participants assessed for the outcomes in this meta-analysis were 1 268 676 of which 13 886 were PLHIV. Overall, the estimated effect of HIV on mortality suggested some worsening (OR 1.3, 95% CI: 0.9 – 2.0, I2 = 78.6%) with very weak evidence against the model hypothesis at this sample size. However, in individuals aged <60 years, the estimated effect on mortality suggested more worsening in PLHIV (OR 2.7, 95% CI: 1.1 - 6.5, I2 = 95.7%) with strong evidence against the model hypothesis at this sample size. HIV was also associated with an estimated effect on hospitalization for COVID-19 that suggested worsening (OR 1.6, 95% CI: 1.3-2.1, I2 = 96.0%) also with strong evidence against the model hypothesis at this sample size. A secondary analysis of the included studies suggested no difference, by HIV status, in the prevalence of pre-existing conditions.
Conclusion
People living with HIV have higher risk of death and hospitalisation from COVID-19, compared to individuals without HIV. A secondary analysis suggests this is not due to associated comorbid conditions. The difference in mortality is exaggerated in those younger than 60 years of age.
Registration
PROSPERO: CRD42020221311 (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221311">https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221311</ext-link>)
Evidence before this study
Findings from existing studies have shown conflicting evidence concerning the risk of severe COVID-19 and death from COVID-19 in people living with HIV (PLHIV) compared to people without HIV. Evidence from three existing systematic reviews suggests that the risk of severe COVID-19 and death from COVID-19 in PLHIV may be similar to that in individuals without HIV. However, findings from three large cohort studies and one meta-analysis of four studies suggest that the risk of death from COVID-19 in PLHIV may be higher than that in individuals without HIV. One of the large cohort studies, which is also included in the previous meta-analysis, consisted of individuals with unknown COVID-19 status, and therefore there is still debate concerning the risk of severe COVID-19 outcomes in PLHIV.
Added value of this study
In this meta-analysis of 11 studies with 1 268 676 individuals with confirmed COVID-19, we found a stronger difference in mortality by HIV status for those individuals below the age of 60 years, and over this age, HIV had an attenuated effect on mortality, suggesting that age-related mortality overshadows PLHIV related mortality. Further, PLHIV had increased odds of being hospitalized and needing intensive cares services, probably related to increased COVID-19 severity in PLHIV. A secondary analysis of the included studies suggested no difference in the prevalence of pre-existing conditions.
Implications of all the available evidence
Our findings suggest that PLHIV are at higher risk than the general population and should be prioritized for vaccine coverage and monitoring if diagnosed with COVID-19. This is especially important for countries in Sub-Saharan Africa that have a high burden of HIV in the younger populations who are more vulnerable.
Strengths
This study was carried out rigorously following the PRISMA guidelines for systematic reviews and meta-analyses. We used a comprehensive search strategy across most of the main citation databases to ensure that no relevant studies were missed. We included studies where participants had confirmed COVID-19 only and we synthesized the findings from studies using a bias adjustment model that took into consideration the quality of included studies.
Limitations
All studies included in this review are observational studies and conclusions about causality require cautious interpretation. Due to a lack of data from included studies, we were not able to analyse the effect of being on treatment for HIV, and HIV control variables such as viral load and CD4 counts on COVID-19 hospitalization, intensive care services and mortality. Lastly most of the included studies had small samples overall or for PLHIV and this may affect the effect estimates in this analysis. Future research is therefore indicated to confirm these findings.
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