Remdesivir for the Treatment of Covid-19 - Final Report Beigel, John H; Tomashek, Kay M; Dodd, Lori E ...
New England journal of medicine/The New England journal of medicine,
11/2020, Letnik:
383, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.
We conducted a ...double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval CI, 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).
Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases ...Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009–2013 has been incorporated into this document.
Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its ...safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log
copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.
Alcohol use among people living with HIV (PLWH) can reduce adherence and worsen health outcomes. We evaluated the economic cost of an effective smartphone application (HealthCall) to reduce drinking ...and improve antiretroviral adherence among heavy-drinking PLWH participating in a randomized trial.
Participants were randomized to receive a brief drinking-reduction intervention, either (a) the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Clinician's Guide (CG-only,
= 37), (b) CG enhanced by HealthCall to monitor daily alcohol consumption (CG+HealthCall,
= 38), or (c) motivational interviewing delivered by a nonclinician enhanced by HealthCall (MI+HealthCall,
= 39). We used micro-costing techniques to evaluate start-up costs and incremental costs per participant incurred from the health care sector perspective in 2018 U.S. dollars. We also investigated potential cost offsets using participant-reported health care utilization.
Participants attended three intervention visits, and each visit cost on average $29 for CG-only, $32 for CG+HealthCall, and $15 for MI+HealthCall. The total intervention cost per participant was $94 for CG-only, $114 for CG+HealthCall, and $57 for MI+HealthCall; the incremental cost of CG+HealthCall compared with CG-only was $20 per participant, and the incremental savings of MI+HealthCall compared with CG-only was $37 per participant. No significant differences in health care utilization occurred among the three groups over 12 months.
The cost of enhancing CG with the HealthCall application for heavy-drinking PLWH was modestly higher than using the CG alone, whereas MI enhanced with HealthCall delivered by a nonclinician had a lower cost than CG alone. HealthCall may be a low-cost enhancement to brief interventions addressing alcohol use and antiretroviral adherence among PLWH.
Mycoplasma genitalium (MG) is an emerging sexually transmitted infection. Treatment of MG is complicated by increasing resistance to primary treatment regimens, including macrolides and ...fluoroquinolones. Understanding the various clinical presentations and relative effectiveness of treatments for MG is crucial to optimizing care.
Patients with a positive MG nucleic acid amplification test between July 1, 2019, and June 30, 2021, at a large health system in New York City were included in a retrospective cohort. Demographics, clinical presentations, coinfections, treatment, and follow-up microbiologic tests were obtained from the electronic medical record. Associations with microbiologic cure were evaluated in bivariate and multivariable logistic regression models.
Five hundred two unique patients had a positive MG nucleic acid amplification test result during the study period. Male individuals presented predominantly with urethritis (117 of 187 63%) and female individuals with vaginal symptoms (142 of 315 45%). Among patients with follow-up testing who received a single antibiotic at the time of treatment, 43% (90 of 210) had persistent infection and 57% (120 of 210) had microbiologic cure. Eighty-two percent of patients treated with moxifloxacin had microbiologic cure compared with 41% of patients receiving azithromycin regimens ( P < 0.001). In multivariable analysis, treatment with moxifloxacin was associated with 4 times the odds of microbiologic cure relative to low-dose azithromycin (adjusted odds ratio aOR, 4.18; 95% confidence interval, 1.73-10.13; P < 0.01).
Clinical presentations of MG vary, with urethritis or vaginal symptoms in most cases. Among patients who received a single antibiotic, only treatment with moxifloxacin was significantly associated with microbiologic cure relative to low-dose azithromycin.
Heavy drinking among people living with HIV (PLWH) reduces ART adherence and worsens health outcomes. Lengthy interventions are not feasible in most HIV care settings, and patients infrequently ...follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed HealthCall as an electronic means of increasing patient involvement in a brief intervention to reduce drinking and improve ART adherence. The objective of the current study is to evaluate the efficacy of HealthCall to improve ART adherence among PLWH who drink heavily when paired with two brief interventions: the National Institute on Alcoholism and Alcohol Abuse (NIAAA) Clinician’s Guide (CG) or Motivational Interviewing (MI). Therefore, we conducted a 1:1:1 randomized trial among 114 participants with alcohol dependence at a large urban HIV clinic. Participants were randomized to one of three groups: (1) CG only (n = 37), (2) CG and HealthCall (n = 38), or (3) MI and HealthCall (n = 39). Baseline interventions targeting drinking reduction and ART adherence were ~ 25 min, with brief (10–15 min) booster sessions at 30 and 60 days. The outcome was ART adherence assessed using unannounced phone pill-count method (possible adherence scores: 0–100%) at 30-day, 60-day, 3, 6, and 12 months. Analyses were conducted using generalized linear mixed models with pre-planned contrasts. Of the 114 enrolled patients, 58% were male, 75% identified as Black/African American, 28% were Hispanic, and 62% had less than a high school education. The mean age was 47.5 years (standard deviation SD 10 years) and the mean number of years since they were diagnosed with HIV was 18.6 (SD 7.6). Participants assigned to HealthCall to extend the CG had increased levels of ART adherence at 60-day and 6-month follow-up (compared to CG only), although there was no statistically significant difference by 12-month follow-up. Participants who were assigned to HealthCall to extend the MI never had statistically significant higher levels of ART adherence. These results suggest that the use of a smartphone app can be used to initially extend the reach of a brief drinking intervention to improve ART adherence over a short period of time; however, sustained long-term improvements in ART adherence after intervention activity ends remains a challenge.
Abstract
We performed anorectal testing in 18 cis-gender men who have sex with men with symptoms consistent with mpox virus (MPXV) infection. We found rectal MPXV DNA in 9/9 with and 7/9 without ...proctitis. Future study of anorectal testing is needed and may inform the diagnosis and pathogenesis of MPXV disease.
The widespread use of facemasks has been a crucial element in the control of the SARS‐CoV‐2 pandemic. With mounting evidence for mask efficacy against respiratory infectious diseases and greater ...acceptability of this intervention, it is proposed that masking should continue after the pandemic has abated to protect some of our most vulnerable patients, recipients of stem cell and solid organ transplants. This may involve not only masking these high‐risk patients, but possibly their close contacts and the healthcare workers involved in their care. We review the evidence for mask efficacy in prevention of respiratory viruses other than SARS‐CoV‐2 and address the burden of disease in transplant recipients. Although we acknowledge that there are limited data on masking to prevent infection in transplant recipients, we propose a framework for the study and implementation of routine masking as a part of infection prevention interventions after transplantation.
Background. PRO 140 is a humanized CCR5 monoclonal antibody that has demonstrated potent antiviral activity when it is administered intravenously to adults infected with CCR5-tropic (R5) human ...immunodeficiency virus type 1 (HIV-1). This study is the first to evaluate subcutaneous administration. Methods. A randomized, double-blind, placebo-controlled study was conducted among 44 subjects with HIV-1 RNA levels of >5000 copies/mL, CD4+ cell counts of >300 cells/µL, no receipt of antiretroviral therapy for ⩾12 weeks, and only R5 HIV-1 detectable. Subjects received placebo, 162 mg of PRO 140, or 324 mg of PRO 140 weekly for 3 weeks or 324 mg of PRO 140 every other week for 2 doses by means of subcutaneous infusion. Subjects were monitored for 58 days for safety, antiviral effects, and PRO 140 serum concentrations. Results. Subcutaneous PRO 140 demonstrated potent and prolonged antiretroviral activity. Mean log10 reductions in HIV-1 RNA level were 0.23, 0.99 ( P = .009), 1.37 (P<.001), and 1.65 (P<.001) for the placebo, 162 mg weekly, 324 mg biweekly, and 324 mg weekly dose groups, respectively. Viral loads remained suppressed between successive doses. Treatment was generally well tolerated. Conclusions. This trial demonstrates proof of concept for a monoclonal antibody administered subcutaneously in HIV-1 infected individuals. Subcutaneous PRO 140 offers the potential for significant dose-dependent HIV-1 RNA suppression and infrequent patient self-administration. Trial registration. ClinicalTrials.gov identifier: NCT00642707.
Abstract
Mpox caused a global outbreak in 2022. Among 249 people who received mpox vaccination at a sexual health clinic in the Bronx, New York, those with private vs public insurance were more ...likely to complete the series. No mpox cases were seen during follow-up at a median 121 days (IQR, 97–139).
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