Antiviral Activity and Safety of Darunavir/Cobicistat for the Treatment of COVID-19

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>We aimed to evaluate the antiviral activity and safety of darunavir/cobicistat (DRV/c) in treating COVID-19 patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In this single-center, randomized, and open-label trial, mild patients with polymerase chain reaction (PCR)–confirmed COVID-19 were enrolled in Shanghai, China. Participants were randomized to receive DRV/c for 5 days on the top of interferon alpha 2b inhaling or interferon alpha 2b inhaling alone. The primary end point was the virological clearance rate of oropharyngeal swabs at day 7 after randomization in the intention-to-treat population (clinicaltrials.gov: NCT04252274).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>From January 30, 2020, to February 6, 2020, a total of 30 patients were enrolled, of whom 18 (60%) were male, aged 47.2 ± 2.8 years; 63.3% (19/30) of the participants had fever, and 46.7% (14/30) had cough at enrollment. The participants were randomized (range) at 4 (2–5) days after onset of symptoms. The proportion of negative PCR results at day 7 was 46.7% (7/15) and 60.0% (9/15) in the DRV/c and control groups (P = .72), respectively. The viral clearance rate at day 3 was 20% (3/15) in both study groups, while the number increased to 26.7% (4/15) in the DRV/c group and remained 20% (3/15) in the control group at day 5. Fourteen days after randomization, 1 participant in the DRV/c group progressed to critical illness and discontinued DRV/c, while all the patients in the control group were stable (P = 1.0). The frequencies of adverse events in the 2 groups were comparable.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Five days of DRV/c did not increase the proportion of negative conversion vs standard of care alone, although it was well tolerated.</jats:p> </jats:sec>

Lack of Benefit in COVID-19 Patients Treated with Hydroxychloroquine or Chloroquine: A Systematic Review and Meta-Analysis

“…<3 days or 3-7 days) contributed to shorter time to undetectable viral RNA by RT-PCR. In contrast, two recently reported RCTs on HCQ from Chen J et al and Tang W et al did not reveal a higher proportion of viral clearance in patients admitted to hospital with mainly mild to moderate COVID-19 than standard of care alone [8,22]. Our primary meta-analysis revealed a positive effect of HCQ/CQ on viral clearance by RT-PCR testing.…”

“…An open label non-randomized clinical trial on 36 patients revealed more rapid viral clearance by HCQ administration [7]. In contrast, a simultaneously reported small size random control trial (RCT) on 30 patients from China did not show an accelerated viral clearance by HCQ [8]. Another study on 62 patients showed that HCQ signi cantly improved the recovery of pneumonia assessed by chest CT scan, but the endpoints of viral clearance and mortality were not evaluated in this study [9].…”

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

“…Two trials compared convalescent plasma added to standard care versus standard care alone [ 40 , 52 ]. The remaining trials and comparisons included hydroxychloroquine with and without azithromycin added to standard care versus standard care alone [ 55 ], hydroxychloroquine versus placebo [ 54 , 68 ], hydroxychloroquine and chloroquine added to standard care versus standard care alone [ 49 ], methylprednisolone added to standard care versus standard care alone [ 57 ], lopinavir–ritonavir versus umifenovir and versus standard care [ 41 ], favipravir versus umifenovir [ 34 ], high-flow nasal oxygenation versus standard mask oxygenation prior to fibreotic tracheal intubation [ 45 ], α-lipoic acid versus placebo [ 47 ], the combination of novaferon plus lopinavir–ritonavir versus novaferon and versus lopinavir–ritonavir [ 46 ], baloxavir marboxil versus favipiravir and versus standard care [ 42 ], 5 versus 10 days of remdesivir [ 38 ], interferon β-1a added to standard care versus standard care alone [ 37 ], colchicine added to standard care versus standard care alone [ 50 ], high-dosage with low-dosage chloroquine diphosphate [ 51 ], intravenous immunoglobulin added to standard care versus standard care alone [ 58 ], ribavirin plus interferon alpha versus lopinavir/ritonavir plus interferon alpha versis ribavirin plus lopinavir/ritonavir plus interferon alpha [ 62 ], darunavir/cobicistat plus interferon alpha-2b versus interferon alpha-2b alone [ 61 ], lincomycin HCl versus azitromycin [ 63 ], 99mTc-methyl diphosphonate (99mTc-MDP) injection added to standard care versus standard care alone [ 64 ], and interferon alpha-2b plus gamma versus interferon alpha-2b alone [ 65 ].…”

“…The first is a network meta-analysis just published in BMJ [ 77 ]. However, at the time of publication, this project did not include all relevant trials [ 50 , 52 , 54 – 56 , 59 – 61 , 64 ], including the pivotal trials assessing the effects of hydroxychloroquine [ 54 , 55 , 59 ].…”

Potential diagnostics and therapeutic approaches in COVID-19

“…Darunavir is a second generation of HIV-1 protease inhibitors used to prevent SARS-CoV-2 infection in-vitro [70] by inhibiting viral replication at 300 μM and this inhibition efficiency was 280-fold compared to the untreated group.…”