by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer

June 18, 2024

Featured Literature:

Roen AO, Peters L, Wandeler G, et al.  Chronic liver enzyme elevation and use of contemporary ARVs among persons living with HIV.  Open Forum Inf Dis.  2024 June 8.  Online ahead of print.   

Data from participants in the International Cohort Consortium of Infectious Diseases (RESPOND) collaboration were analyzed to determine chronic liver enzyme elevation (cLEE) incidence and associated factors, focusing on commonly prescribed contemporary ARVs.  cLEE was defined as chronic ALT elevations greater than the upper limit of normal (ULN) at two or more visits across at least six months and within two years of baseline.  People newly initiating DTG, RAL, EVG/c, BIC, boosted DRV or ATV, RPV, or EFV were considered for inclusion (TDF and TAF use was also examined).  17,106 individuals who initiated a new ARV after 2012 had complete data.  Overall, 1,932 (11.3%) developed cLEE during 87,924 PYFU; this corresponded to an incident rate (IR) of 22.0/1000 PYFU.  51% had less then Grade 1 severity (>ULN to 1.25x ULN) and 40% had Grade 1 (1.25-2.5x ULN).  Investigators did not observe any cumulative association between longer ARV use and cLEE for any of the considered ARVs.  For all ARVs of interest, cLEE IR was highest in the first 6-12 months after medication initiation and declined thereafter.  No association was observed between use of any INSTIs and cLEE; TDF use was associated with increased risk, and use of boosted DRV was associated with decreased risk.  Viral hepatitis status, dyslipidemia, and BMI were also associated with cLEE.

Author’s Commentary:

Chronic liver enzyme elevation remains prevalent with currently used ARVs.  This large multi-national study, which included people initiating newer INSTIs and followed for a median of 5 years, observed generally low-grade ALT elevations particularly in the first year after new ARV initiation.  After adjustment, INSTI initiation was not associated with short-term risk of cLEE.  Consistent with prior studies, use of EFV, RPV, and TDF in this cohort were associated with increased risk of cLEE (point estimates for EFV and RPV were not significant however).  Although this analysis is limited by lack of additional detail (i.e., exposure to known hepatotoxic substances) and minimal participant diversity (> 75% were European males), it is reassuring to note that liver enzyme changes were modest and appeared to stabilize/improve after the first year. 

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