People with HIV with CD4 counts below 350 were almost three times more likely to experience severe COVID-19 symptoms than people with higher CD4 counts, confirming warnings by the British HIV Association and the European AIDS Clinical Society that immunosuppressed people with HIV are likely to be at higher risk of serious illness.
The findings, published in the journal HIV Medicine, come from an analysis of all cases of SARS-CoV-2 infection diagnosed in people with HIV receiving care at hospitals in Madrid, Milan and 16 German cities. The study reports on 175 cases of symptomatic COVID-19 confirmed by PCR or antibody testing identified in these cohorts up to 12 June 2020 (details of the Madrid cases, published previously, are reported here).
Seventy-two per cent of cases were mild-to-moderate (no pneumonia or mild pneumonia). The remainder were severe (blood oxygen saturation 93% or below, raised respiratory rate, or lung infiltrates above 50%) (33 people) or critical (respiratory failure, multiple organ failure or septic shock) (16 people). Seven people died during the follow-up period.
The study population was largely male (82%), White (88%) and under 60 years old (64%). The median CD4 count was 663, 69% had a CD4 count over 500 and only 18% had a CD4 cell count below 350. All except one were on antiretroviral treatment and 94% had a viral load below 50 copies/ml at last measurement. Only three people had viral loads above 1000 copies/ml.
Co-morbidities were common in the study population; one-third had at least two co-morbidities associated with increased COVID-19 risk (including cardiovascular disease, type 2 diabetes, hypertension, cancer, chronic kidney disease or chronic lung disease) and a further 27% had one co-morbidity.
However, 39% of all COVID-19 patients – and 24% of those with severe or critical COVID-19 – had no co-morbidities and only 16% of those who developed severe or critical COVID-19 were obese, another important risk factor for severe COVID-19.
Researchers assessed the risk of severe or critical COVID-19 illness according to age, gender, ethnicity, current and nadir CD4 count, viral load below 50 copies/ml, prior AIDS diagnosis, co-morbidities, body mass index and presence of tenofovir or a protease inhibitor in the antiretroviral regimen.
Univariate analysis showed that co-morbidities, age over 50 years, nadir CD4 count below 200 and current CD4 count below 350 each raised the risk of severe or critical COVID-19. But in a multivariate analysis that controlled for other risk factors, co-morbidities and age were no longer associated with an increased risk of severe or critical illness.
Multivariate analysis showed that a current CD4 count below 350 was the only factor associated with severe or critical illness (odds ratio 2.85, 95% CI 1.26-6.44), p = 0.01).
The only factor associated with an increased risk of death was a nadir (lowest ever) CD4 count below 200 but as the number of deaths was low, the researchers did not carry out a multivariate analysis.
Antiretroviral regimen did not affect the risk of severe illness; tenofovir, found to be protective against COVID-19 in one study, did not protect against severe illness in this study and nor did any protease inhibitor.
"These findings suggest that low current CD4 count may be a good reason for early vaccination even if other health conditions are not present."
This sample is not a systematic study of all people receiving care at these HIV clinics; it represents only those who developed symptoms of COVID-19 and underwent testing. The study doesn’t capture asymptomatic infections or people who may have been unwell but did not seek testing or medical care, so the findings probably overestimate the frequency of severe and critical illness.
Nevertheless, the fact that those sick enough to seek medical care and testing were three times more likely to have a severe illness if they had a CD4 count below 350 will reinforce warnings that people with HIV with low CD4 counts are at higher risk of COVID-19. Analyses from a US registry and from New York came to similar conclusions.
The findings also have implications for COVID-19 vaccination programmes.
Current United Kingdom COVID-19 vaccination guidance puts all people with HIV in priority group 6 but people with CD4 counts below 200 and other health conditions or a low nadir CD4 count can be moved into priority group 4 at their HIV clinic’s request (to be vaccinated by mid-February). These findings suggest that low current CD4 count may be a good reason for early vaccination even if other health conditions are not present.
On 15 January, European HIV medical associations including the European AIDS Clinical Society and the British HIV Association recommended that people with CD4 counts below 350 should be prioritised for COVID-19 vaccination. They note that current guidance about prioritisation of people with HIV for vaccination varies between European countries.
As to why a low CD4 count raises the risk of severe illness, the study authors say that robust virus-specific CD4 responses are needed to clear viral infections. Any disturbance of T-cell responses could impair the ability to fight viral infections and rein in “exuberant and overzealous early innate responses to coronaviruses”.
Hoffman C et al. Immune deficiency is a risk factor for severe COVID-19 in people living with HIV. HIV Medicine, online ahead of print, 27 December 2020 (open access).