Abstract: Research Letters
AIDS 2023, 37:1481–1489
No association between use of tenofovir disoproxil
fumarate, etravirine, or integrase-strand transfer
inhibitors and acquisition or severe outcomes of
SARS-CoV-2 infection in people with HIV in
the Netherlands
Myrthe L. Verburgha,b,c,d, Marc van der Valka,b,e,
Bart J.A. Rijndersf, Peter Reissa,b,d,g
and Ferdinand W.N.M. Wita,b,e
See related paper on page 1473
In two Dutch observational cohorts of people with
HIV, the use of TDF, ETR, or INSTIs was not
independently associated with either the risk
of incident SARS-CoV-2 infection or severe
COVID-19 outcomes, as was suggested by previous
observational and molecular docking studies. Our
findings do not support a strategy of modifying
antiretroviral therapy to include these agents to
protect against SARS-CoV-2 infection and severe
COVID-19 outcomes.
Since the start of the COVID-19 pandemic, several studies
have tried to determine factors associated with acquisition
of and clinical outcome of SARS-CoV-2 infection in
people with HIV (PWH). Recent observational studies
have suggested a protective effect of tenofovir disoproxil
fumarate (TDF) against acquisition of SARS-CoV-2 [1,2]
and severe COVID-19 outcomes [1,3,4], whereas other
studies found no benefit of TDF or tenofovir alafenamide
(TAF) in PWH [5,6] or adults without HIV [7,8].
Etravirine (ETR) and the integrase-strand transfer
inhibitors (INSTIs) – specifically raltegravir (RAL) and
dolutegravir (DTG) – were proposed as potential
inhibitors of two major SARS-CoV-2 proteins in a
molecular docking [9] and molecular dynamics simulation
study [10]. One recent study showed that in-vitro docking
by SARS-CoV-2 to the ACE2 receptor is inhibited by
DTG and ETR [11]. Thus far, no studies in PWH have
reported epidemiological evidence for a protective effect
of the use of INSTIs or ETR against acquiring SARSCoV-2 infection and severe COVID-19 outcomes.
We investigated the association between the abovementioned antiretrovirals and incident SARS-CoV-2
infection and COVID-19-associated hospitalization and/
or death in two Dutch observational cohorts of PWH.
First, we used data from the COVID-19 substudy of the
AGEhIV cohort collected from September 2020 until
April 2021 [12]. PWH and participants without HIV
were assessed every 6 months for incident SARS-CoV-2
infection. Incident SARS-CoV-2 infection was defined
as positive combined IgA/IgM/IgG SARS-CoV-2
nucleocapsid (N) antibody assay or a self-reported
positive PCR test in participants without detectable
N-antibodies. We previously reported that younger age
and sub-Saharan African origin, but not HIV-status, were
independently associated with higher risk of incident
SARS-CoV-2 infection. However, we did not investigate
the association with specific antiretrovirals in PWH.
Second, we used data from the Dutch national observational HIV cohort (ATHENA), containing data of more
than 95% of PWH in care in one of the 24 HIV-treatment
centers in the Netherlands [13]. Within this cohort, we
recently reported that the risk of severe COVID-19
outcomes was increased in individuals with uncontrolled
HIV replication, low CD4þ cell count and prior AIDS,
independently of general risk factors such as age,
comorbidity burden, and non-Western origin (F.W.N.
M. Wit, P. Reiss, B. Rijnders, M. van der Valk, in
preparation), but potential associations with specific
antiretrovirals were not extensively analyzed.
Extending our earlier analyses, we now assessed whether
use of..
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