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| SYSTEMATIC REVIEW AND META-ANALYSIS (ORIGINAL ARTICLE)
|Year : 2020 | Volume
| Issue : 4 | Page : 313-323
Safety and efficacy of lopinavir/ritonavir combination in COVID-19: A systematic review, meta-analysis, and meta-regression analysis
Anusuya Bhattacharyya1, Subodh Kumar2, Phulen Sarma2, Hardeep Kaur2, Manisha Prajapat2, Nishant Shekhar2, Seema Bansal2, Pramod Avti3, Mythili Hazarika4, Saurabh Sharma2, Dhruv Mahendru2, Ajay Prakash2, Bikash Medhi2
1 Department of Ophthalmology, Government Medical College and Hospital, Sector 32, Chandigarh, India
2 Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
3 Department of Biophysics, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
4 Department of Psychiatry, Gauhati Medical College and Hospital, Guwahati, Assam, India
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).
Dr. Bikash Medhi
Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
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