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Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2–5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov , NCT05582629 , and has been completed. A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04–1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04–1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Men who have sex with men (MSM) have recently accounted for an alarmingly increasing proportion of HIV-1 transmission in China. In order to investigate the immune status as a result of CRF01_AE infection and CXCR4 co-receptor usage in a young Shanghai-based HIV-1-infected MSM population in Shanghai, 364 HIV-1-infected MSM with average age of 22.7 years old, newly diagnosed between Jan 2009 and Jul 2013 were analyzed for CD4+T cell count, subtyping using phylogenetic analysis, and viral co-receptor tropism using Geno2pheno and webPSSM in combination. A total of 276 individuals were identified as recently infected. Subtype assignment were as follows: 176 (63.8%) CRF01_AE, 77 (27.9%) CRF07_BC, and 23 (8.3%) subtype B. Besides, 24 second-generation recombinant strains were identified. A lower CD4+T cell count at baseline survey was observed among CRF01_AE strain-infected individuals, compared to those who were infected with CRF07_BC (P<0.01). The frequency of baseline CD4+T cell count <200 was higher and the frequency of CD4 T counts >500 lower in CRF01_AE infection than CRF07_BC infection. It is worth noting that 32.4%–40.9% of CRF01_AE strain-infected individuals were predicted to carry CXCR4-tropic viruses whereas none of CRF07_BC and subtype B were found to be as CXCR4-tropic viruses (P<0.001). As could be expected CXCR4 tropism was associated with lower CD4 T counts. This study revealed that CRF01_AE strains with high frequency of CXCR4 tropism are prevailing in the young MSM population in China and could potentially cause a severe loss of CD4+T cell count and rapid disease progression. A regular surveillance of HIV-1 subtypes, CD4+T cell count and viral co-receptor usage would be greatly beneficial for effectively monitoring disease progression, improvement of antiretroviral therapy strategy and prompt intervention of transmission. [ABSTRACT FROM AUTHOR]