Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa.

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve

Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management

Prashini Moodley, Patrick D. J. Sturm, Trusha Vanmali, David Wilkinson, Cathy Connolly and A. Willem Stur

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve