Clinical question What is the role of drugs in preventing covid-19? Why does this matter? There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. Recommendation The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). How this guideline was created This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Understanding the new recommendation The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. Updates This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. Readers note This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

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High-dose Rifampicin regimens have been shown to be more effective for tuberculosis (TB) treatment in TB/HIV co-infected patients. This study assessed the hepatic safety of a high-dose Rifampicin regimen among TB/HIV co-infected patients. 811 TB/HIV co-infected patients, antiretroviral treatment (ART) naïve, at least 18 years old with a CD4 T-cell count between 50 and 350 cells/mm 3 were enrolled. Patients with multidrug-resistant tuberculosis were excluded. Patients had received first-line antituberculosis treatment followed by ART after two weeks (arm A) or two months (arm B). In arm C, they received antituberculosis treatment with a high dose of Rifampicin (15 mg/kg/day instead of 10 mg/kg/day) during the TB intensive phase of treatment and ART after two months. The patients performed transaminases (ALT, AST), γ-glutamyl transpeptidase (γ-GT), alkaline phosphatase (ALP), and total bilirubin blood tests. The study outcomes were an elevation of ALT at least 5 times the Upper Limit of Normal (Primary outcome), an isolated elevation grade 4 of AST, γ-GT, ALP, and/or total bilirubin (Secondary outcomes). The patients included were 53.97% men and 2.44% co-infected hepatitis B or C virus. There were no significant differences between ALT, AST, γ-GT, ALP, and total bilirubin between the standard regimens (Arms A and B) and high dose Rifampicin regimen (Arm C). This study showed that a high-dose Rifampicin regimen for TB treatment in TB/HIV co-infected patients was as safe as that of a standard regimen.

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