HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform

Abstract

Background: Whether HIV infection is associated with risk of death due to COVID-19 is unclear. We aimed to investigate this association in a large-scale population-based study in England.

Methods: We did a retrospective cohort study. Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. We included all adults (aged ≥18 years) alive and in follow-up on Feb 1, 2020, and with at least 1 year of continuous registration with a general practitioner before this date. People with a primary care record for HIV infection were compared with people without HIV. The outcome was COVID-19 death, defined as the presence of International Classification of Diseases 10 codes U07.1 or U07.2 anywhere on the death certificate. Cox regression models were used to estimate the association between HIV infection and COVID-19 death; they were initially adjusted for age and sex, then we added adjustment for index of multiple deprivation and ethnicity, and then for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities, and calendar time.

Results: 17 282 905 adults were included, of whom 27 480 (0·16%) had HIV recorded. People living with HIV were more likely to be male, of Black ethnicity, and from a more deprived geographical area than the general population. 14 882 COVID-19 deaths occurred during the study period, with 25 among people with HIV. People living with HIV had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2·90 (95% CI 1·96-4·30; p<0·0001). The association was attenuated, but risk remained high, after adjustment for deprivation, ethnicity, smoking and obesity: adjusted HR 2·59 (95% CI 1·74-3·84; p<0·0001). There was some evidence that the association was larger among people of Black ethnicity: HR 4·31 (95% CI 2·42-7·65) versus 1·84 (1·03-3·26) in non-Black individuals (p-interaction=0·044).

Interpretation: People with HIV in the UK seem to be at increased risk of COVID-19 mortality. Targeted policies should be considered to address this raised risk as the pandemic response evolves.

Funding: Wellcome, Royal Society, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, Health Data Research UK.

Figure 1

Study profile

Figure 2

Cumulative COVID-19 mortality during the study period by HIV status with 95% CI, standardised to covariate distribution of the HIV group Note that cumulative COVID-19 mortality is not restricted to individuals infected with severe acute respiratory syndrome coronavirus 2 but rather represents the cumulative incidence of acquiring infection and then progressing to death with COVID-19 listed as a cause. Cumulative mortality predicted from a Royston-Parmar model including age, sex, index of multiple deprivation, ethnicity, smoking, and obesity, with the baseline hazard parametrised as a three-degrees-of-freedom cubic spline; predictions standardised to the covariate distribution of the HIV group. This analysis was done for individuals with complete ethnicity data only, because computational limitations prevented implementation in the dataset with multiply imputed ethnicity.

Figure 3

HRs for the association between HIV and COVID-19 mortality All stratified models (by age, sex, ethnicity, comorbidities, epidemic period) were adjusted for age, sex, IMD, ethnicity. IMD=index of multiple deprivation. HR=hazard ratio. *Black is defined as self-report as African, Caribbean, or other Black; a similar pattern was seen in a direct comparison between Black (HR 4·81, 95% CI 2·63–8·80) and white (2·02, 1·05–3·89) among individuals with complete ethnicity data. † Comorbidities refers to diagnosed hypertension, chronic respiratory disease, asthma, chronic cardiac disease, diabetes, non-haematological cancer, haematological cancer, chronic liver disease, stroke and dementia, other neurological disease, reduced kidney function, organ transplant, asplenia, rheumatoid arthritis, lupus, and psoriasis, and other immunosuppressive conditions; the model stratified by comorbidities was additionally adjusted for these comorbidities as individual covariates; excluding hypertension from the list of comorbidities gave stratified HRs of 1·57 (0·59–4·20) for individuals without comorbidities and 2·52 (1·64–3·87) for those with comorbidities (p-interaction=0·39). ‡Days from Feb 1, 2020; the three categories were chosen to capture the period before social distancing policies in the UK would have affected mortality, the period of peak COVID-19 mortality, and the period during which restrictions began to be eased.