Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Young adults HIV-1 infected by vertical transmission in southern Brazil - Clinical, demographic, and virological features.

Combination antiretroviral therapy promotes longer life expectancy, making it possible for perinatally HIV-infected patients to achieve adulthood. Past therapy was not always optimized, suggesting that virological and host features may also play a role in survival. The aim of this study is to describe characteristics of HIV disease progression associated with virological features in adolescents perinatally that were HIV infected. A case series was conducted including 81 patients that were in follow-up at Hospital de Clínicas/Universidade Federal do Paraná, Curitiba, Brazil. Venous blood was collected to conduct tropism and viral subtype assays. The median age was 19 years old (interquartile range 18-21), and a majority of patients were female (54.3%). Viral subtype was obtained for 66 (82%) patients, and subtypes B and C were found in 34% and 59%, respectively. Tropism assay was conducted in 55 (67%) patients: 71% were R5 and 29% X4. Distribution of viral tropism and subtype shows a significant association of subtype C with R5 tropism. Subtype C is more prevalent in southern Brazil and also in the population infected with HIV by vertical transmission. Both R5 tropism and subtype C are associated with slower progression to AIDS. The survival of these patients may be related to virological features present in a benign pattern of disease progression.