Lower CD4 count and unsuppressed HIV raise the risk for severe COVID-19

A detectable viral load together with a CD4 count below 500 put people with HIV at greater risk of severe COVID-19, a study of COVID-19 cases in 16 Spanish hospitals reported yesterday at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

The study also found that having multiple co-morbidities – conditions such as high blood pressure, cardiovascular disease, chronic kidney disease, cancer or high blood pressure – greatly raised the risk of a severe outcome, confirming findings from other studies in people with HIV and the general population.

Several large studies have shown that people with HIV have an increased risk of severe COVID-19 and dying from COVID-19, including a global study presented at IAS 2021 by the World Health Organization. What’s less clear is whether factors such as viral load, immune suppression or underlying health conditions place some people with HIV at higher risk than others.

To investigate the impact of these factors on the risk of severe COVID-19 outcomes, Spanish researchers looked for COVID-19 cases in 13,142 people with HIV currently receiving care at 16 hospitals in the Spanish province of Catalonia. The cohort is predominantly male (81%), middle-aged (median age 47 years), virally suppressed (81%) and living with at least one underlying condition (65% had one or more co-morbidities, including 23% who had three or more). The median CD4 count in the cohort is 692.

The researchers identified 749 people (5.7% of the cohort) diagnosed with SARS-CoV-2 (confirmed by nucleic acid testing, antigen or antibody test) up to 15 December 2020. Of these, 103 (13.8%) were admitted to hospital with COVID-19, including seven admitted to an intensive care unit. Thirteen people admitted to hospital died of COVID-19; 12 of these deaths occurred in people who were not admitted to an intensive care unit.

People with HIV were more likely to be diagnosed with SARS-CoV-2 if they were migrants (34% of the cohort was born outside Spain) (adjusted hazard ratio, 1.55 [95% confidence interval, 1.31-1.83]), gay or bisexual men (aHR 1.42 [95% CI, 1.09-1.86]) or if they had at least four co-morbidities (aHR, 1.46 [95% CI, 1.09-1.97]). People who inject drugs were significantly less likely to be diagnosed with SARS-CoV-2 (aHR 0.66 [0.44-0.98]) compared to the rest of the population.

People with HIV aged 75 or over were three and a half times more likely to have severe COVID-19 outcomes (hospitalisation or death) compared to younger people (aHR, 3.57 [95% CI, 1.21-10.51]). Migrants had a higher risk of severe COVID-19 outcomes too (aHR, 2.34 [95% CI, 1.46-3.75]).

"The risk factors highlighted in the study should be used to prioritise people with HIV for COVID-19 vaccination."

When the researchers looked at which chronic co-morbidities were associated with severe COVID-19, they found that the chronic conditions that raised the risk of severe COVID-19 in other studies – diabetes, high blood pressure, cardiovascular disease and obesity – were not associated with an increased risk in their cohort when considered separately.

Instead, in a multivariate analysis that controlled for sex, age, country of origin, socioeconomic deprivation, HIV transmission group, antretroviral therapy backbone, HIV viral load and CD4 cell count, they found that neuropsychiatric co-morbidity, autoimmune disease, respiratory disease and metabolic disease were the only independent factors that raised the risk of a severe outcome. Metabolic disease was defined as disturbances in metabolism in this study, including lipid elevations, thyroid and endocrine disorders, to distinguish from diabetes or hypertension.

However, they also found that each additional co-morbidity was associated with a substantial increase in the risk of a severe COVID-19 outcome. People with one co-morbidity were almost six times more likely to have a severe outcome compared to people without co-morbidities (aHR 5.90 [95% CI 1.97-17.65]). People with four or more co-morbidities were 22 times more likely to have a severe outcome compared to people without comorbidities (aHR 22.63 [95% CI 7.42-68.97]).

The researchers also looked at the relationship between CD4 count, viral load and severe COVID-19 outcomes. They found that whereas CD4 count did not affect the risk of severe COVID-19 in people with suppressed viral load, in people with detectable viral load, a CD4 count below 500 was associated with an increased risk of a severe outcome (p<0.039). The median CD4 count in people who died of COVID-19 was 469 (interquartile range 250-587).

Presenting the study, Dr Daniel Nomah concluded that the risk factors highlighted in the study should be used to prioritise people with HIV for COVID-19 vaccination, with people who have unsuppressed viral load and low CD4 counts, as well as those with a high number of co-morbidities in special need of vaccination.