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Review 1: "HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform"

This study is an important effort to add to the literature on COVID-19 mortality rates among HIV-positive individuals; however, the extremely small relevant sample size, and a number of confounders, make its specific policy implications suspect.

Published onSep 16, 2020
Review 1: "HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform"
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key-enterThis Pub is a Review of
HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform

Background: It is unclear whether HIV infection is associated with risk of COVID-19 death. We aimed to investigate this in a large-scale population-based study in England. Methods: Working on behalf of NHS England, we used the OpenSAFELY platform to analyse routinely collected electronic primary care data linked to national death registrations. People with a primary care record for HIV infection were compared to people without HIV. COVID-19 death was defined by ICD-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, initially adjusted for age and sex, then adding adjustment for index of multiple deprivation and ethnicity, and finally for a broad range of comorbidities. Interaction terms were added to assess effect modification by age, sex, ethnicity, comorbidities and calendar time. Results: 17.3 million 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. There were 14,882 COVID-19 deaths during the study period, with 25 among people with HIV. People living with HIV had nearly three-fold higher risk of COVID-19 death than those without HIV after adjusting for age and sex (HR=2.90, 95% CI 1.96-4.30). The association was attenuated but risk remained substantially raised, after adjustment for deprivation and ethnicity (adjusted HR=2.52, 1.70-3.73) and further adjustment for comorbidities (HR=2.30, 1.55-3.41). There was some evidence that the association was larger among people of black ethnicity (HR = 3.80, 2.15-6.74, compared to 1.64, 0.92-2.90 in non-black individuals, p-interaction=0.045) Interpretation: HIV infection was associated with a markedly raised risk of COVID-19 death in a country with high levels of antiretroviral therapy coverage and viral suppression; the association was larger in people of black ethnicity.

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.



This is a well done secondary analysis of large health system data sets to evaluate whether persons with HIV infection are at increased risk of death from COVID-19. The results are important and deserve to be published. I have some concerns about how the authors present and interpret their results.

The authors seem intent on exaggerating the strength and public helath importance of their findings. They summarize their findings as showing a “markedly raised risk of COVID-19 death among persons with HIV.” In fact, the crude risk ratio is 1.05 (2.34/2.22), a number that the authors don’t even present. After adjustment for just age and sex, this goes up to 2.90. After adjusting for other available covariates, this goes down to 2.30 and to 1.93 for those with complete data.

Although this is a study of millions of people and almost 15,000 COVID-19 deaths, the results are entirely based on only 25 deaths among persons with HIV. Of these 25, 23 had other known risk factors for COVID mortality. The point estimate for risk of death for persons with HIV and no comorbidities was 1.02; there were only two such deaths. The authors gloss over this finding and don’t even mention it in the text, saying instead that they lack statistical power to prove an interaction. But that is a sample size problem, and this is the best estimate of risk according to their data.

The authors suggest a need for targeted policies for persons with HIV, such as priority for a future vaccine. The correct conclusion from this study is that persons with HIV but without other comorbidities are at little or no additional risk compared to their peers without HTV. Those with HIV and other comorbidities do appear to be at increased risk, but it is not clear if and how this should alter policy. A hazard ratio of somewhere between 1.05 and 2.90, depending on how many factors one adjusts for, is of scientific interest, but it is a relatively weak risk factor compared to others.

I particularly object to their figure 2. It presents smoothed out modeled data (instead of presenting the real data that they have), apparently in an attempt to create a false impression of strong rigorous data. In fact, it conveys no additional information beyond the hazard ratios that were already presented.

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