Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial.

BACKGROUND: The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve clinical outcomes of patients admitted to the hospital with severe COVID-19. METHODS: We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio [OR] greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT [mITT] population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278. FINDINGS: 447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 [95% CI 0·94-1·97], p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups. INTERPRETATION: In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19. FUNDING: COALITION COVID-19 Brazil and EMS.

Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19.

BACKGROUND: Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited. METHODS: We conducted a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed. RESULTS: A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval [CI], 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent. CONCLUSIONS: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).

Knowledge about STD/AIDS and sexual behavior among high school students in Rio de Janeiro, Brazil.

The incidence of AIDS and other sexually transmitted diseases (STDs) is increasing among adolescents. In order to better understand high-risk sexual behavior among students, a cross-sectional study based on a self-answered anonymous questionnaire was conducted in 10 public and private high schools in Rio de Janeiro, Brazil. Data were obtained on sociodemographics, knowledge of STD/AIDS, and sexual behavior. Among 945 students aged 13-21, 59% were sexually initiated, and the median age at first sexual intercourse was 15 years (range: 7-19). Although 94% reported being aware of the need for condom use for protection, only 34% informed always using condoms during sex. Low family income was associated with unsatisfactory knowledge (OR = 9.40; 95% CI = 6.05-14.60) and inconsistent condom use (OR = 11.60; 95% CI = 5.54-24.30). However, unsatisfactory knowledge was not associated with inconsistent condom use. School-based educational programs should focus on sexual behavior more than on transmission of knowledge, as well as targeting low-income students.

Knowledge about STD/AIDS and sexual behavior among high school students in Rio de Janeiro, Brazil

The incidence of AIDS and other sexually transmitted diseases (STDs) is increasing among adolescents. In order to better understand high-risk sexual behavior among students, a cross-sectional study based on a self-answered anonymous questionnaire was conducted in 10 public and private high schools in Rio de Janeiro, Brazil. Data were obtained on sociodemographics, knowledge of STD/AIDS, and sexual behavior. Among 945 students aged 13-21, 59 percent were sexually initiated, and the median age at first sexual intercourse was 15 years (range: 7-19). Although 94 percent reported being aware of the need for condom use for protection, only 34 percent informed always using condoms during sex. Low family income was associated with unsatisfactory knowledge (OR = 9.40; 95 percent CI = 6.05-14.60) and inconsistent condom use (OR = 11.60; 95 percent CI = 5.54-24.30). However, unsatisfactory knowledge was not associated with inconsistent condom use. School-based educational programs should focus on sexual behavior more than on transmission of knowledge, as well as targeting low-income students