RESUMO
Background At the peak of the coronavirus disease 2019 (COVID-19) pandemic, the need for an orally administered agent to prevent the progression of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became increasingly evident, which was the impetus behind our investigations with molnupiravir. Molnupiravir has been shown to be effective in preventing hospitalizations and/or clinical complications in patients with mild-to-moderate COVID-19. In this study, we evaluate the efficacy and safety of molnupiravir in Indian patients with mild SARS-CoV-2 infection and at least one risk factor for disease progression (CTRI/2021/05/033739). Methodology This was a phase III, multicenter, randomized, open-label, controlled study conducted in Indian adults aged 18-60 years with mild SARS-CoV-2, reverse transcription polymerase chain reaction (RT-PCR)-positive within 48 hours of enrollment in the study, and within five days of first symptom onset. Enrolled patients were randomized to treatment arms in a 1:1 ratio to receive molnupiravir or placebo in addition to the standard of care (SoC) for SARS-CoV-2 infection. The SoC was in compliance with Government of India guidelines that were in force at the time. The primary endpoint was the rate of hospitalization up to day 14. Safety endpoints included incidence of adverse events (AEs). Results Eligible patients were randomized in a 1:1 ratio to receive molnupiravir in addition to SoC treatment (n = 608) or SoC alone (n = 610). In the molnupiravir group, nine (1.48%) patients required hospitalization versus 26 (4.26%) patients in the control group (risk difference = -2.78%; 95% CI = -4.65, -0.90; p = 0.0053). Overall, 45 (3.70%) patients reported 47 AEs during the study, most of which were mild and resolved completely. The molnupiravir group reported 30 AEs compared to 17 AEs in the control group. Headache and nausea were the two most commonly reported AEs. Conclusions The molnupiravir arm showed a lower rate of hospitalization and a shorter time for the improvement of clinical symptoms coupled with early RT-PCR negativity. Molnupiravir was well tolerated, and AEs were mild and rare. The addition of molnupiravir to standard therapy has the potential to prevent the progression of mild COVID-19 disease to the severe form.
RESUMO
BACKGROUND: Virological monitoring (VM) and drug resistance (DR) analysis are crucial for effective HIV management. Due to the high cost of commercial assays, VM and DR analysis is not performed in resource-limited-settings. OBJECTIVE: The objective of this study is to develop a pooling based algorithm for the combined identification of virologic treatment failure (VTF) by nucleic acid testing (NAT) and DR by sequencing - NAT+DR assay. STUDY DESIGN: We enrolled 559 participants on first-line therapy and analyzed for VTF. The virologically suppressed participants were followed-up to see the VTF prevalence (>1000 copies/mL) and DR by the NAT+DR pooling. Each pool comprising 5 plasma samples were amplified by targeting reverse transcriptase gene, if found positive, the pool was deconvoluted and samples were individually tested for HIV RNA and DR. Assay characteristics of NAT+DR assay were calculated in comparison with commercial assay. RESULTS: Of 559 participants, 67 had VTF at baseline and were excluded. Of the remaining 478 participants, 325 returned for follow-up and NAT+DR assay was performed for them. Of 65 pools tested, 13 pools were positive. On deconvolution 14 individuals were found to have VTF. Sensitivity, specificity, positive predictive value and negative predictive value was 100%, relative efficiency was 59% and 87% & 85% cost was saved for identifying VTF and combined identification of VTF and DR, respectively. CONCLUSIONS: Pooled NAT+DR assay is likely a good strategy to drastically reduce the cost and sustainability of the VM and can thereby facilitate the scale-up of successful HIV treatment programs, and reduce unnecessary switching to second-line drugs in resource-limited-settings.
