Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

IntroductionRecent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub-Saharan Africa and review possible interventions.MethodsWe defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART). We conducted a systematic review of data from studies conducted in sub-Saharan Africa and published between 2000 and June 2011 for four of these steps and performed a meta-analysis when indicated; existing data syntheses were used for the remaining two steps.ResultsThe World Health Organization estimates that only 39% of HIV-positive individuals are aware of their status. Among patients who know their HIV-positive status, just 57% (95% CI, 48 to 66%) completed assessment of ART eligibility. Of eight studies using an ART eligibility threshold of≤200 cells/µL, 41% of patients (95% CI, 27% to 55%) were eligible for treatment, while of six studies using an ART eligibility threshold of≤350 cells/µL, 57% of patients (95% CI, 50 to 63%) were eligible. Of those not yet eligible for ART, the median proportion remaining in pre-ART care was 45%. Of eligible individuals, just 66% (95% CI, 58 to 73%) started ART and the proportion remaining on therapy after three years has previously been estimated as 65%. However, recent studies highlight that this is not a simple linear pathway, as patients cycle in and out of care. Published studies of interventions have mainly focused on reducing losses at HIV testing and during ART care, whereas few have addressed linkage and retention during the pre-ART period.ConclusionsLosses occur throughout the care pathway, especially prior to ART initiation, and for some patients this is a transient event, as they may re-engage in care at a later time. However, data regarding interventions to address this issue are scarce. Research is urgently needed to identify effective solutions so that a far greater proportion of infected individuals can benefit from long-term ART.

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Future research to develop cheap, point-of-care diagnostic tests will allow a greater understanding of T. vaginalis epidemiology. In addition, the effect of treatment on outcome of pregnancy and HIV acquisition requires further study. This will in turn facilitate operational studies evaluating optimal control strategies and their impact on the complications of T. vaginalis.