1. Safety and efficacy of lopinavir/ritonavir combination in COVID-19: A systematic review, meta-analysis, and meta-regression analysis.
- Author
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Bhattacharyya A, Kumar S, Sarma P, Kaur H, Prajapat M, Shekhar N, Bansal S, Avti P, Hazarika M, Sharma S, Mahendru D, Prakash A, and Medhi B
- Subjects
- COVID-19, Drug Combinations, Humans, Negative Results, Pandemics, Treatment Outcome, COVID-19 Drug Treatment, Antiviral Agents therapeutic use, Coronavirus Infections drug therapy, Lopinavir therapeutic use, Pneumonia, Viral drug therapy, Ritonavir therapeutic use
- Abstract
Background: Being protease inhibitors and owing to their efficacy in SARS-CoV, lopinavir + ritonavir (L/R) combination is being used in the management of COVID-19. In this systematic review and meta-analysis, we have evaluated the comparative safety and efficacy of L/R combination., Materials and Methods: Comparative, observational studies and controlled clinical trials comparing L/R combination to standard of care (SOC)/control or any other antiviral agent/combinations were included. A total of 10 databases were searched to identify 13 studies that fulfilled the predefined inclusion/exclusion criteria., Results: No discernible beneficial effect was seen in the L/R group in comparison to SOC/control in terms of "progression to more severe state" (4 studies, odds ratio [OR]: 1.446 [0.722-2.895]), "mortality" (3 studies, OR: 1.208 [0.563-2.592]), and "virological cure on days 7-10" (3 studies, OR: 0.777 [0.371-1.630]), while the L/R combination arm performed better than the SOC/control arm in terms of "duration of hospital stay" (3 studies, mean difference (MD): -1.466 [-2.403 to - 0.529]) and "time to virological cure" (3 studies, MD: -3.272 [-6.090 to - 0.454]). No difference in efficacy was found between L/R versus hydroxychloroquine (HCQ) and L/R versus arbidol. However, in a single randomized controlled trail (open label), chloroquine (CQ) performed better than L/R. The combination L/R with arbidol may be beneficial (in terms of virological clearance and radiological improvement); however, we need more dedicated studies. Single studies report efficacy of L/R + interferon (IFN, either alpha or 1-beta) combination. We need more studies to delineate the proper effect size. Regarding adverse effects, except occurrence of diarrhea (higher in the L/R group), safety was comparable to SOC., Conclusion: In our study, no difference was seen between the L/R combination and the SOC arm in terms of "progression to more severe state," "mortality," and virological cure on days 7-10;" however, some benefits in terms of "duration of hospital stay" and "time to virological cure" were seen. No significant difference in efficacy was seen when L/R was compared to arbidol and HCQ monotherapy. Except for the occurrence of diarrhea, which was higher in the L/R group, safety profile of L/R is comparable to SOC. Compared to L/R combination, CQ, L/R + arbidol, L/R + IFN-α, and L/R + IFN-1β showed better efficacy, but the external validity of these findings is limited by limited number of studies (1 study each)., Competing Interests: None
- Published
- 2020
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