No antiretroviral protects against COVID-19, Dutch study finds

Bits And Splits/ Image is for illustrative purposes only.

Antiretroviral treatment with tenofovir disoproxil fumarate (TDF), etravirine or an integrase inhibitor does not reduce the risk of acquiring SARS-CoV-2 or severe COVID-19, according to an analysis of two Dutch national cohorts published in the journal AIDS.

The findings disagree with a Spanish study, published in 2022, which found that TDF was associated with a reduced risk of hospitalisation with severe COVID-19 in people with HIV over the age of 50.  They also contradict the findings of a US study that showed a reduced risk of symptomatic or severe COVID-19 in people taking TDF.

Dr Myrthe Verburgh and colleagues at Amsterdam University Medical Centers looked at associations between antiretroviral treatment and COVID-19 risks in the AGEhIV cohort and ATHENA, the Dutch national observational HIV cohort. As well as investigating the effect of TDF treatment on COVID-19 risk, they were also interested in determining whether several antiretrovirals identified as inhibitors of SARS-CoV-2 cell entry in laboratory studies had an impact on COVID-19 risk. These agents were the non-nucleoside reverse transcriptase inhibitor etravirine and HIV integrase inhibitors, especially dolutegravir and raltegravir.



The presence of one or more additional health conditions at the same time as a primary condition (such as HIV).

integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.


Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

The AGEhIV cohort consisted of 239 people with HIV aged over 45, with a median age of 62 years, followed between September 2020 and April 2021 to determine the incidence of SARS-CoV-2 and hospitalisation due to COVID-19. Participants had been living with HIV for a median of 21 years, all but one was virally suppressed and the median CD4 count was 670. During the follow-up period, 29 of 239 people acquired SARS-CoV-2.

After controlling for age, sex at birth, ethnicity, co-morbidities, viral load, CD4 count and prior AIDS, the researchers found no reduction in the risk of either SARS-CoV-2 infection or severe COVID-19 associated with any antiretroviral in the AGEhIV cohort.

The ATHENA cohort includes 98% of all people with HIV in the Netherlands. There were 2189 participants who were diagnosed with COVID-19 while receiving antiretroviral treatment. Their median age was 50 years, they had been living with HIV for a median of 12 years, the median CD4 count was 710 and 98% had suppressed viral load. Severe COVID-19 was diagnosed in 158 people; of these, 29 died.

The risk of severe COVID was greater in older people, those of non-White origin, people with more co-morbidities and those living with HIV for longer. People diagnosed with severe COVID-19 had lower median CD4 counts and were more likely to be taking a protease inhibitor. But after adjusting for risk factors, the researchers found no association between any antiretroviral drug and reduced or increased risk of acquiring SARS-CoV-2 or severe COVID-19.

The Dutch researchers say that studies which control for confounding factors including co-morbidities, age, ethnicity and metabolic disease consistently show no association between antiretroviral treatment and protection from infection or severe COVID.

In an accompanying editorial comment, Dr Nicola Abrescia of the Hospital for Infectious Diseases ‘D. Cotugno’, Naples, questions the idea of adjusting an antiretroviral regimen that is controlling HIV to include drugs with anti-SARS-CoV-2 activity before an infection occurs. The first line of defence should be SARS-CoV-2 vaccination, she comments. If infection does take place, drugs proven to be effective against SARS-CoV-2 (remdesivir or nirmaltrevir/ritonavir) should be started within five days of the onset of symptoms.