Suboptimal HIV treatment raises the risk of COVID-19 death in South Africa

People with HIV who have low CD4 counts, or unsuppressed viral load, no history of HIV treatment, or active tuberculosis, were more likely to die of COVID-19 than other people with HIV, a large study of COVID-19 deaths in South Africa’s Western Cape province has reported.

The study investigators at the University of Cape Town say that ensuring that people with HIV are on fully suppressive antiretroviral treatment and have been vaccinated should be public health priorities for prevention of deaths from COVID-19.

Their findings have been made available as a pre-print, which means they have not been peer reviewed yet.

Several studies have shown that people with HIV have a slightly higher risk of dying from COVID-19 than the rest of the population. Almost all studies have looked at outcomes in people admitted to hospital with COVID-19 and were conducted in high-income settings. However, there is limited information about the risk factors for COVID-19 mortality in the entire population of people with HIV in settings where HIV prevalence is high and access to healthcare is restricted.

The Western Cape study is the largest investigation of COVID-19 risks in people with HIV. The study investigators looked for all COVID-19 cases diagnosed by laboratory testing in people using public health care facilities in the province until March 2022. Each individual receiving care in the province has a unique identifier that allows anonymised data to be compiled from multiple sources. This enabled researchers to track COVID-19 diagnoses, deaths, HIV status, COVID-19 vaccination status and other medical conditions in the province.

This study looked at which people with HIV were at higher risk of dying of COVID-19. Approximately 600,000 people with HIV received care in the province at least once in the three years up to March 2022. Of these, 18,120 were diagnosed with SARS-CoV-2 (the virus that causes COVID-19) by antigen or PCR test during the first three waves of the pandemic, up to November 2022. Almost three-quarters (71%) were female.

Just under six percent (5.7%) of people with HIV who were diagnosed with SARS-CoV-2 died of COVID-19 during the first three waves of the pandemic.

In line with the rollout of vaccines, the proportion of people with HIV diagnosed with SARS-CoV-2 who had been vaccinated increased from 4% during the third wave to 39% during the fourth wave.

The researchers divided people with HIV diagnosed with SARS-CoV-2 into two groups, those aged 15-39 years and those aged 40 and over. They looked at the risk factors associated with dying from COVID-19 in people after a first diagnosis of SARS-CoV-2. This analysis excluded subsequent cases because experiencing a first SARS-CoV-2 infection might provide a degree of protection against serious illness in those who recover. Including these cases could skew the results, what epidemiologists call a ‘selection bias’.

The death rate was higher in people aged 40 and over compared to younger people (8.6% vs 2.9%).

In those over 40 (8,675 cases), older age was associated with an increased risk of death. People with HIV over 70 had almost five times the risk of dying from COVID-19 compared to those aged 40-49, but the impact of age on the risk of death was less pronounced in those under 40.

In people under 40 (9,146 cases), active tuberculosis or TB in the past year, chronic kidney disease and diabetes each substantially increased the risk of death. People with high blood pressure had a slightly higher risk of dying. The same conditions increased the risk of death in people aged 40 and over, but the increase in risk was smaller than in the under-40s. People aged 35-39 were around twice as likely to die from COVID-19 as people aged 15-24.

Almost five percent of those diagnosed with SARS-CoV-2 had active tuberculosis (the analysis did not distinguish between people receiving and not receiving TB treatment). People with active TB had a seven times greater risk of death from COVID-19 than people with no history of TB if they were under 40, but a 3.3-times greater risk if they were over 40.

Pregnancy did not affect the risk of dying from COVID-19.

"People who had received the full course of their vaccine were 90% less likely to die compared to unvaccinated people."

Vaccination against COVID-19 began in May 2021 in South Africa in the over-60s and was progressively extended until everyone aged 12 and over was eligible for vaccination by October 2021.

Although the numbers vaccinated in each age range were small, sufficient people aged 40 and over had been vaccinated to show a significant difference between vaccinated and unvaccinated people, even in the first month after vaccination. People who had received their first vaccine shot less than 28 days before being diagnosed with SARS-CoV-2 were 50% less likely to die of COVID-19 than unvaccinated people. People who had received the full course of their vaccine (one dose of the Johnson & Johnson vaccine or two doses of other vaccines) were 90% less likely to die compared to unvaccinated people.

Factors related to HIV raised the risk of death in both younger and older people. A CD4 count below 50, indicating very advanced HIV, increased the risk of death 3.3 times in both age groups compared to a CD4 count above 500. A CD4 count between 50 and 199 doubled the risk of death from COVID-19 compared to a CD4 count above 500.

Compared with people with HIV who had a viral load below 1,000 copies/ml (defined as suppressed), those under 40 with a viral load above 1,000 copies/ml had a 53% higher risk of death. Viral load did not affect the risk of dying from COVID-19 in those aged 40 and over.

Not being on antiretroviral treatment (defined as not having collected medication before SARS-CoV-2 diagnosis) increased the risk of dying from COVID-19 by 48% in people aged 40 and over. Not being on treatment did not raise the risk of death in the under-40s.

In settings where HIV prevalence is high, these findings are especially significant because the number of people with untreated or poorly controlled HIV is greater. In Western Cape, nine percent of people diagnosed with SARS-CoV-2 during the first three waves of the pandemic had a viral load above 1,000 copies/ml.

It’s unclear if having a detectable viral load makes it more likely that people with HIV will acquire SARS-CoV-2, but if they do, those under the age of 40 have a higher risk of dying from COVID-19, the study found. The authors say that ensuring people are on suppressive antiretroviral treatment and being treated for comorbidities, especially TB, should be priorities for limiting COVID-19 deaths in a context where vaccination access and uptake may be suboptimal. The study authors also highlight the need for access to antiviral treatments for COVID-19 for people with HIV with severe illness. Low CD4 count and unsuppressed viral load “should be considered when prioritizing patients for anti-SARS-CoV-2 therapy,” they conclude.