Abstract: Open Forum Infectious Diseases
CORRESPONDENCE
Reply to: “Antiviral Activity and
Safety of Darunavir/Cobicistat
for Treatment of COVID-19”
enzyme elevations (40.4% DRVr vs 27.1%
non-DRVr; P = .011), creatinine increase
(9.3% vs 6.2%; P = .3), microbiologically
documented bloodstream, pulmonary,
or urinary infections (19.9% vs 17.5%;
P = .59), cardiovascular disorders (13.2%
vs 14.1%; P = .81), and mild diarrhea
(11/151, 7.3%, vs 1/177, 0.6%; P = .001).
In the DRV/r group, diarrhea and liver
enzyme elevations were regarded as possibly or probably associated with DRV/r.
In no case was DRVr withdrawn due to an
AE. In the multivariate time-dependent
analysis, DRV/r did not affect the risk of
developing AEs (Table 1).
Overall, 98 (29.9%) patients died of
COVID-19. DRV/r did not affect the risk
of death (adjHR, 1.32; 95% CI, 0.85–2.06;
P = .21) (Table 1).
Although we administered DVR with
a different booster (ritonavir instead of
cobicistat), our experience in a real-life
cohort adds some evidence to the findings of Chen et al., given the large proportion of severe COVID-19 and the
older age of patients we evaluated. First,
a short-term course of DRV/r was well
tolerated, as it did not increase the risk
of AEs. Differences in concomitant SOC
treatments, AE reporting, and study population might explain the higher grade
4–5 AE rate we found with respect to
Chen et al. (11.9% vs 0%). Second, DRV/r
did not influence overall mortality, while
respiratory insufficiency, both at baseline and during treatment, and systemic
inflammation did. Notably, Chen et al.
did not report any death at 14 days of follow-up. The 29.9% in-hospital mortality
rate we found may reflect the more severe
clinical presentation and the older age of
our cohort.
In conclusion, although well tolerated even in patients with severe
COVID-19, DRV/r did not reduce mortality in COVID-19. Further studies are
CORRESPONDENCE • ofid • 1
Dear Editor,
Chen and colleagues evaluated the antiviral activity and safety of darunavir/
cobicistat
(DRV/c)
in
treating
coronavirus-associated disease 2019
(COVID-19) in a randomized open-label
study in 30 patients [1]. The authors did
not observe any benefit in virological
clearance, but there was no increase in
side effects. However, severe/critical patients were not included; thus, as the authors stated, their findings may be not
applicable to this population. Therefore,
we report our results on the safety of
darunavir/ritonavir (DRV/r) in 328
adults with COVID-19, most of whom
had severe pneumonia.
In this study, we included HIVnegative patients consecutively hospitalized for COVID-19 between February
28 and March 29, 2020, who received
the following standard of care (SOC):
hydroxychloroquine (HCQ; 400 mg
twice daily for 5–20 days), short-term
initial antibiotic coverage, and anti-inflammatory treatment with tocilizumab
and/or methylprednisolone. The patients
admitted between February 28, 2020,
and March 23, 2020, also received DRV/r
800/100 mg once daily for 5–10 days if
not contraindicated (ie, severe cardiac
or liver disease); as of March 24, 2020,
we stopped using DRV/r based on data
from recent studies showing inefficacy of
lopinavir/ritonavir [2, 3].
Patients with a ratio between arterial oxygen partial pressure and fraction of inspired oxygen (PaO2/FiO2)
≤300 mmHg or pulse oxygen saturation
≤90% at resting were classified as severe
cases [4]...
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