Background: Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens.
Methods: In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation.
Results: Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]).
Conclusions: Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075031 | PMC |
| http://dx.doi.org/10.1093/cid/ciaa244 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Concoctive principles of detoxification and retention of the main toxic hepatotoxicity of Tripterygium wilfordii and its anti-inflammatory efficacy by concocting with the medicinal excipient Spatholobi Caulis juice.
Fitoterapia
January 2025
College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China; Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Medicine, Zhengzhou 450046, China. Electronic address:
Tripterygium wilfordii (TW), which has severe hepatotoxicity, is commonly used as anti-rheumatism. Using the juice of auxiliary herbs in concocting poisonous herbs is a conventional method for toxicity reduction or efficacy enhancement. Traditional Chinese Pharmacy textbooks record that Spatholobi Caulis (SC) can alleviate the side effects caused by TW and also possesses excellent hepatoprotective effect.
View Article and Find Full Text PDFα-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation.
Ecotoxicol Environ Saf
January 2025
Department of Forensic Medicine, School of Forensic Medicine, Kunming Medical University, Kunming, China. Electronic address:
Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β.
View Article and Find Full Text PDFHow Often Is Rifampin Therapy Initiated and Completed in Patients With Periprosthetic Joint Infections?
Clin Orthop Relat Res
January 2025
Department of Medicine, Duke University, Durham, NC, USA.
Background: Rifampin therapy is indicated for the treatment of staphylococcal periprosthetic joint infection (PJI) in patients who have undergone debridement, antibiotics, and implant retention (DAIR) or one-stage revision as per the Infectious Diseases Society of America (IDSA) guideline. Given the well-established effectiveness of rifampin as adjunctive therapy in staphylococcal PJI, it is crucial to evaluate its utilization in practice and identify factors that contribute to its underuse or incomplete administration, as these deviations may undermine treatment efficacy and patient outcomes.
Questions/purposes: Among patients who met clear indications for rifampin use having undergone DAIR or one-stage revision for staphylococcal PJI, (1) what proportion of patients did not receive it? (2) What proportion of patients started it but did not complete the planned course? (3) Where documented in the medical record, what were the common reasons for not using it or prematurely discontinuing it, and in what percentage of the patients' charts was no reason given? (4) What proportion of patients were taking a medication that put them at risk for a drug-drug interaction (DDI)?
Methods: Using an institutional database, patients who underwent DAIR or revision arthroplasty for PJI from January 2013 to April 2023 were identified (n = 935).
Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.
Liver Int
February 2025
Department of Clinical Pharmacology and Toxicology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
Targeted therapies and immunotherapies have shown great promise as best-in-class treatments for several cancers with respect to efficacy and safety. While liver test abnormalities are rather common in patients treated with kinase inhibitors or immunotherapy, events of severe hepatotoxicity in these patients are rare in comparison with those associated with chemotherapeutics. The underlying mechanisms and risk factors for severe hepatotoxicity with novel oncology therapies are not well understood, complicating the drug-induced liver injury (DILI) risk assessment in the preclinical and clinical phases of drug development.
View Article and Find Full Text PDFAntituberculosis Therapy-Induced Acute Liver Failure in a Renal Transplant Recipient: A Case Report.
Cureus
December 2024
Nephrology, University Clinical Center of Serbia, Belgrade, SRB.
To prevent organ rejection, renal transplant (RT) recipients must take immunosuppressive medicines, which make them more susceptible to infections such as tuberculosis (TB). Hepatotoxicity, which can vary from asymptomatic increased liver enzymes to severe liver failure, is the most prevalent side effect of first-line antituberculosis (AT) drugs. Treating TB in RT patients involves unique concerns since AT medications might interact with immunosuppressive medications, potentially reducing efficacy or increasing toxicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!