Efficacy of Lopinavir–Ritonavir Combination Therapy for the Treatment of Hospitalized COVID-19 Patients: A Meta-Analysis

Deng, Jiawen; Zhou, Fangwen; Hou, Wenteng; Heybati, Kiyan; Ali, Saif; Chang, Oswin; Silver, Zachary; Dhivagaran, Thanansayan; Ramaraju, Harikrishnaa Ba; Wong, Chi Yi; Zuo, Qi; Lapshina, Elizabeth; Mellett, Madeline

doi:10.2217/fvl-2021-0066

Cited by 16 publications

(11 citation statements)

References 116 publications

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“…Specifically, the efficacy and safety of several antiviral therapies, as well as immunomodulatory regimens, have been thoroughly investigated and described in the literature. However, many of the antiviral therapies, such as chloroquine, lopinavir–ritonavir, and ivermectin, have been consistently shown in randomized controlled trials (RCTs) and meta-analyses to confer little to no clinical efficacy against SARS-CoV-2 [ 1 – 3 ]. Meanwhile, immunomodulatory agents such as dexamethasone were found to only be effective among patients with severe disease receiving respiratory support, with little to no efficacy in patients with mild symptoms [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

et al. 2022

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Purpose To assess and compare the relative efficacy and safety of anti-SARS-CoV-2 antibody regimens for COVID-19. Methods This systematic review and random-effects network meta-analysis was conducted according to PRISMA-NMA. Literature searches were conducted across MEDLINE, EMBASE, PubMed, Web of Science, CENTRAL, and CNKI up to February 20th, 2022. Interventions were ranked using P scores. Results Fifty-five RCTs ( N = 45,005) were included in the review. Bamlanivimab + etesevimab (OR 0.13, 95% CI 0.02–0.77) was associated with a significant reduction in mortality compared to standard of care/placebo. Casirivimab + imdevimab reduced mortality (OR 0.67, 95% CI 0.50–0.91) in baseline seronegative patients only. Four different regimens led to a significant decrease in the incidence of hospitalization compared to standard of care/placebo with sotrovimab ranking first in terms of efficacy (OR 0.20, 95% CI 0.08–0.48). No treatment improved incidence of mechanical ventilation, duration of hospital/ICU stay, and time to viral clearance. Convalescent plasma and anti-COVID IVIg both led to a significant increase in adverse events compared to standard of care/placebo, but no treatment increased the odds of serious adverse events. Conclusion Anti-SARS-CoV-2 mAbs are safe, and could be effective in improving mortality and incidence of hospitalization. Convalescent plasma and anti-COVID IVIg were not efficacious and could increase odds of adverse events. Future trials should further examine the effect of baseline seronegativity, disease severity, patient risk factors, and SARS-CoV-2 strain variation on the efficacy of these regimes. Registration PROSPERO-CRD42021289903. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-022-01825-8.

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Section: Introductionmentioning

confidence: 99%

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

et al. 2022

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“…The study by Wen et al (2020) [ 38 ] demonstrated that LPV/r did not promote virus negative conversion and clinical improvement in COVID-19 patients [ 39 ]. An updated systematic review examined whether the use of LPV/r could be more favorable compared to the standard therapies regarding the length of stay, time for positive-to-negative conversion of SARS-CoV-2 and mortality in hospitalized patients with COVID-19, concluding that LPV/r had no significant advantage and also registered a significant increase in the occurrence of side effects [ 40 ]. However, Elmekaty et al [ 41 ] showed that early treatment with LPV/r is associated with a faster clinical improvement and/or virological clearance than the darunavir/cobicistat therapy in patients with COVID-19 pneumonia, and that the safety profile was quite comparable.…”

Section: Antiviral Drugsmentioning

confidence: 99%

Drugs for COVID-19: An Update

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh known human coronavirus, and it was identified in Wuhan, Hubei province, China, in 2020. It caused the highly contagious disease called coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO) on 11 March 2020. A great number of studies in the search of new therapies and vaccines have been carried out in these three long years, producing a series of successes; however, the need for more effective vaccines, therapies and other solutions is still being pursued. This review represents a tracking shot of the current pharmacological therapies used for the treatment of COVID-19.

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“…В наиболее раннем метаанализе исследований за период до мая 2020 г. при сравнении 7 перепрофилированных препаратов для лечения COVID-19 (рибавирин, хлорохин, гидроксихлорохин, умифеновир, фавипиравир, интерферон и лопинавир/ритонавир) показано, что только лопинавир/ ритонавир вызывал наиболее достоверные побочные эффекты со стороны ЖКТ в виде усиления диареи, тошноты и рвоты [46]. В последующих двух метаанализах 2020 и 2022 г. проводилась оценка безопасности непосредственно лопинавира/ ритонавира при лечении госпитализированных пациентов с COVID-19, и основные побочные эффекты также отмечены со стороны ЖКТ -диарея, тошнота, рвота, боль в животе, потеря аппетита и гепатотоксичность в виде повышения уровня печеночных трансаминаз и билирубина [47,48]; ОР неблагоприятных эффектов составил 2,88 (ДИ 1,04-7,95; р<0,01) [48].…”

Section: лопинавир/ритонавирunclassified

Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)

Леонова¹

2022

Consilium Medicum

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The COVID-19 pandemic has posed a challenge for new etiotropic agents, leading to an urgent repurposing of antimicrobial and antiviral drugs to treat a new infection based on the results of in silico, in vitro, in vivo experimental studies, and clinical trials. However, less attention has been paid to the safety of repurposed drugs. Exposure to repurposed drugs with limited risk-benefit evidence in COVID-19 required adaptation of safety monitoring, which affected the completeness and quality of reports, and making causality assessments the most difficult task. A review of data accumulated over the period of the COVID-19 pandemic on the nature of adverse reactions associated with the use of repurposed drugs (hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ribavirin) used in real practice is presented. The results of RCTs and observational studies, systematic reviews and meta-analyses were used. Systematized data on the safety of the use of hydroxychloroquine and chloroquine in patients with COVID-19 in short-term treatment (14 days), including a series of meta-analyses, the risk of adverse effects was increased by 1.52 times; the main manifestations are prolongation of the QT interval and arrhythmias (up to 25%), gastrointestinal disorders (up to 50%), increased levels of bilirubin (3%) and transaminases (up to 10%), dermatological (up to 10%) and neuropsychiatric side effects (up to 21.7%). Most of the side effects of repurposed antiviral drugs of the nucleoside analog group are associated with their direct cytotoxic effect, which is manifested by toxic damage to the gastrointestinal tract, hepatotoxicity, nephrotoxicity, cardiotoxicity, and hematotoxicity. The greatest number of side effects from the gastrointestinal tract and liver were observed for lopinavir/ritonavir in comparison with other drugs. New side effects have been identified for remdesivir when used in the context of the COVID-19 pandemic cardiotoxicity (bradycardia and severe hypotension) and nephrotoxicity, which was regarded by regulatory authorities as a safety signal. To solve the problems of assessing the cause-and-effect relationship, further more thorough research and analysis will be required. The accumulated information in the context of the ongoing COVID-19 pandemic should be subject to ongoing dynamic analysis and published in medical journals to alert clinicians.

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Efficacy of Lopinavir–Ritonavir Combination Therapy for the Treatment of Hospitalized COVID-19 Patients: A Meta-Analysis

Cited by 16 publications

References 116 publications

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

Differential efficacy and safety of anti-SARS-CoV-2 antibody therapies for the management of COVID-19: a systematic review and network meta-analysis

Drugs for COVID-19: An Update

Repurposed antimicrobial and antiviral drugs for COVID-19 treatment: safety and side effects in real clinical practice (scientific review)

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