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Journal of Clinical Immunology Oct 2023Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We...
PURPOSE
Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome.
METHODS
A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models.
RESULTS
A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction.
CONCLUSIONS
AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.
Topics: Humans; Adult; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Reinfection; Autoantibodies; Interferon-gamma; Immunologic Deficiency Syndromes; Opportunistic Infections; Anti-Bacterial Agents
PubMed: 37365453
DOI: 10.1007/s10875-023-01537-0 -
The safety and efficacy of oral antiviral drug VV116 for treatment of COVID-19: A systematic review.Medicine Jul 2023Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the...
BACKGROUND
Recent trials have highlighted the potential of oral antiviral VV116 in the treatment of patients with mild COVID-19. However, no comprehensive studies have assessed the safety and efficacy of VV116. Therefore, we conducted a systematic review to assess the safety and efficacy of VV116.
METHODS
A comprehensive search was conducted on PubMed, Scopus, and Google Scholar websites, with a cutoff date of March 23, to identify pertinent studies.
RESULTS
The results from the 3 included studies indicated that no serious adverse events were reported in the VV116 experimental groups, which exhibited a 2.57-day faster time to viral shedding than the control group and demonstrated non-inferiority to the nirmatrelvir-ritonavir control group in alleviating major symptoms.
DISCUSSION
Collectively, available studies suggest a reliable safety and efficacy profile for VV116. However, the limited number of trials was insufficient for meta-analysis, and the included population consisted of younger individuals with mild and moderate symptoms, not encompassing the elderly who are severely affected by COVID-19. We hope that more studies will be conducted in the future to ensure that VV116 has a more reliable safety and efficacy profile in the clinical setting, especially in severe or critical patients.
Topics: Aged; Humans; Antiviral Agents; COVID-19; Ritonavir
PubMed: 37417593
DOI: 10.1097/MD.0000000000034105 -
Pain Physician Jul 2023The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to... (Meta-Analysis)
Meta-Analysis
A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.
BACKGROUND
The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain.
OBJECTIVES
The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020.
METHODS
Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events.
RESULTS
A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo.
LIMITATIONS
The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors.
CONCLUSIONS
For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated.
CLINICAL TRIAL REGISTRATION INFORMATION
PROSPERO under the identification CRD42020212834.
Topics: Humans; Antiviral Agents; Valacyclovir; Famciclovir; Network Meta-Analysis; Acute Pain; Randomized Controlled Trials as Topic; Acyclovir; Herpes Zoster; Neuralgia, Postherpetic
PubMed: 37535772
DOI: No ID Found -
The Lancet. Infectious Diseases Feb 2024Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure.
METHODS
For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2-3 and between day 0 and days 5-7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680.
FINDINGS
Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2-3 were -0·6 g/dL (95% CI -0·7 to -0·5), -0·7 g/dL (-0·8 to -0·5), -0·6 g/dL (-0·7 to -0·4), and -0·5 g/dL (-0·7 to -0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2-3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias.
INTERPRETATION
Treatment of patients with G6PD activity of 30% or higher with 0·25-0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25-1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses.
FUNDING
Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.
Topics: Humans; Antimalarials; Artemether, Lumefantrine Drug Combination; Artesunate; Australia; Hemoglobins; Hemolysis; Malaria, Vivax; Plasmodium vivax; Primaquine; Prospective Studies; Retrospective Studies
PubMed: 37748497
DOI: 10.1016/S1473-3099(23)00431-0 -
Clinical Infectious Diseases : An... Aug 2023In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma...
Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Liver Neoplasms; Sustained Virologic Response
PubMed: 37579210
DOI: 10.1093/cid/ciad380 -
Journal of Neurology Jul 2023Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Specific antiviral treatment is only available for a small subset of viral encephalitis (VE). Adjunctive steroids are used, but there is scant evidence evaluating its utility. We present a systematic review and meta-analysis on the outcome of steroid use in VE.
METHODS
We conducted a systematic literature review and reported it according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Two observational studies from unpublished or partially published data were added. For the meta-analysis, we employed the metaphor package of the statistical software R-4.3.1.
RESULTS
We screened 378 studies and included 50. 155 patients were added from the Houston and Linz cohorts. Individual data were available for 281 persons, 120 (43%) of whom received steroids. The most common pathogens were herpes simplex virus 1, West Nile virus, and measles. Study designs and patient outcomes were heterogeneous. Only three of the trials report an advantage of steroid therapy. Steroid-induced side effects were scarce. Ten cohorts were included into the meta-analysis. For the pooled data, the null hypothesis could not be rejected (p = 0.245) using a random effects model, i.e., a benefit of steroid treatment on survival in VE could not be shown.
CONCLUSIONS
Steroids as potent anti-inflammatory agents may act through a reduction of secondary inflammation-mediated damage. Our data do not support the use of steroids in VE. However, multiple shortcomings apply. Standardized controlled trials are needed to investigate optimal dosing and timing of steroid administration and to explore potential subgroups that could benefit.
Topics: Humans; Steroids; Anti-Inflammatory Agents; Encephalitis, Viral
PubMed: 37060361
DOI: 10.1007/s00415-023-11715-0 -
Viruses Aug 2023Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced... (Review)
Review
Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs.
Topics: Humans; Acquired Immunodeficiency Syndrome; HIV Infections; Anti-Retroviral Agents; Medication Adherence; Treatment Failure
PubMed: 37632074
DOI: 10.3390/v15081732 -
AIDS (London, England) Aug 2023To identify types, evidence, and study gaps of alternative HIV preexposure prophylaxis (PrEP) care delivery models in the published literature.
OBJECTIVES
To identify types, evidence, and study gaps of alternative HIV preexposure prophylaxis (PrEP) care delivery models in the published literature.
DESIGN
Systematic review and narrative synthesis.
METHODS
We searched in the US Centers for Disease Control and Prevention (CDC) Prevention Research Synthesis (PRS) database through December 2022 (PROSPERO CRD42022311747). We included studies published in English that reported implementation of alternative PrEP care delivery models. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale. Those that met our study criteria were evaluated for efficacy against CDC Evidence-Based Intervention (EBI) or Evidence-Informed Intervention (EI) criteria or Health Resources and Services Administration Emergency Strategy (ES) criteria, or for applicability by using an assessment based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework.
RESULTS
This review identified 16 studies published between 2018 and 2022 that implemented alternative prescriber ( n = 8), alternative setting for care ( n = 4), alternative setting for laboratory screening ( n = 1), or a combination of the above ( n = 3) . The majority of studies were US-based ( n = 12) with low risk of bias ( n = 11). None of the identified studies met EBI, EI, or ES criteria. Promising applicability was found for pharmacists prescribers, telePrEP, and mail-in testing.
CONCLUSIONS
Delivery of PrEP services outside of the traditional care system by expanding providers of PrEP care (e.g. pharmacist prescribers), as well as the settings of PrEP care (i.e. telePrEP) and laboratory screening (i.e. mail-in testing) may increase PrEP access and care delivery.
Topics: Humans; HIV Infections; Delivery of Health Care; Risk; Pre-Exposure Prophylaxis; Anti-HIV Agents
PubMed: 37199602
DOI: 10.1097/QAD.0000000000003601 -
The Journal of Antimicrobial... Jul 2023The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear.
METHODS
We conducted a systematic review until 1 November 2022 searching for randomized controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir [±standard of care (SoC)] versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach.
RESULTS
Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality [risk ratio (RR) 0.27, 95% CI 0.07-1.02, high-certainty evidence] and probably does not reduce the risk for 'hospitalization or death' (RR 0.81, 95% CI 0.55-1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02-1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92-1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50-28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence).
CONCLUSIONS
In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on 'hospitalization or death' and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.
Topics: Humans; COVID-19; SARS-CoV-2
PubMed: 37170886
DOI: 10.1093/jac/dkad132 -
The Cochrane Database of Systematic... Nov 2023Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It... (Review)
Review
BACKGROUND
Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It remains to be evaluated for which indications and patient populations the drug is suitable.
OBJECTIVES
To assess the efficacy and safety of nirmatrelvir/ritonavir plus standard of care (SoC) compared to SoC with or without placebo, or any other intervention for treating COVID-19 or preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register, Scopus, and World Health Organization COVID-19 Research Database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 15 May 2023. This is a LSR. We conduct update searches every two months and make them publicly available on the open science framework (OSF) platform.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology and used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in postexposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from low-income countries and low- to middle-income countries, and people from different ethnic and racial backgrounds.
MAIN RESULTS
As of 15 May 2023, we included two RCTs with 2510 participants with mild and mild to moderate symptomatic COVID-19 in outpatient and inpatient settings comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo. All trial participants were without previous confirmed SARS-CoV-2 infection and at high risk for progression to severe disease. Randomization coincided with the Delta wave for outpatients and Omicron wave for inpatients. Outpatient trial participants and 73% of inpatients were unvaccinated. Symptom onset in outpatients was no more than five days before randomisation and prior or concomitant therapies including medications highly dependent on CYP3A4 were not allowed. We excluded two studies due to concerns with research integrity. We identified 13 ongoing studies. Three studies are currently awaiting classification. Nirmatrelvir/ritonavir for treating people with asymptomatic or mild COVID-19 in outpatient settings Nirmatrelvir/ritonavir plus SoC compared to SoC plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; low-certainty evidence) and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC may reduce serious adverse events during the study period compared to SoC plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to SoC plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably decreases discontinuation of study drug due to adverse events compared to SoC plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No studies reported improvement of clinical status, quality of life, or viral clearance. Nirmatrelvir/ritonavir for treating people with moderate to severe COVID-19 in inpatient settings We are uncertain whether nirmatrelvir/ritonavir plus SoC compared to SoC reduces all-cause mortality at 28 days (RR 0.63, 95% CI 0.21 to 1.86; 1 study, 264 participants; very low-certainty evidence), or increases viral clearance at seven days (RR 1.06, 95% CI 0.71 to 1.58; 1 study, 264 participants; very low-certainty evidence) and 14 days (RR 1.05, 95% CI 0.92 to 1.20; 1 study, 264 participants; very low-certainty evidence). No studies reported improvement or worsening of clinical status and quality of life. We did not include data for safety outcomes due to insufficient and inconsistent information. Subgroup analyses for equity For outpatients, the outcome 'admission to hospital or death' was investigated for equity regarding age (less than 65 years versus 65 years or greater) and ethnicity. There were no subgroup differences for age or ethnicity. For inpatients, the outcome 'all-cause mortality' was investigated for equity regarding age (65 years or less versus greater than 65 years). There was no difference between subgroups of age. No further equity-related subgroups were reported, and no subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available.
AUTHORS' CONCLUSIONS
Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients infected with the Delta variant of SARS-CoV-2. There is low- to moderate-certainty evidence of the safety of nirmatrelvir/ritonavir. Very low-certainty evidence exists regarding the effects of nirmatrelvir/ritonavir on all-cause mortality and viral clearance in mildly to moderately affected, mostly unvaccinated COVID-19 inpatients infected with the Omicron variant of SARS-CoV-2. Insufficient and inconsistent information prevents the assessment of safety outcomes. No reliable differences in effect size and direction were found regarding equity aspects. There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform.
Topics: Humans; Aged; COVID-19; SARS-CoV-2; Ritonavir; COVID-19 Drug Treatment
PubMed: 38032024
DOI: 10.1002/14651858.CD015395.pub3