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Hepatotoxicity and Liver-Related Mortality in Women of Child-Bearing Potential Living With HIV and High CD4 Counts Initiating Efavirenz-Containing Regimens
Clinical Infectious Diseases
Background: Severe hepatotoxicity in people with HIV receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of child-bearing age initiating EFV-containing regimens.
Methods: In the PROMISE trial, ART-naïve pregnant women with HIV and CD4>350 and ALT<2.5 ULN were randomized during the antepartum (AP) and post-partum (PP) periods to ART strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the DAIDS 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 > grade 3, or severe, hepatotoxicity with an incidence of 2.3 (95% confidence interval (CI) 2.0-2.6) per 100 person-years (PY). Events occurred between 1-132 weeks PP. 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, one of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI 0.06-0.08) per 100 PY. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years 1.35 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.
Bhattacharya D, Gupta A, Tierney C, Huang S, Peters MG, Chipato T, Martinson F, Mohtashemi N, Dula D, George K, Chaktoura N, Klingman K, Gnanashanmugam D, Currier JS, Fowler MG. Hepatotoxicity and Liver-Related Mortality in Women of Child-Bearing Potential Living With HIV and High CD4 Counts Initiating Efavirenz-Containing Regimens. Clin Infect Dis. 2020 Mar 12:ciaa244. doi: 10.1093/cid/ciaa244. Epub ahead of print. PMID: 32161944.