NEW ORLEANS, LA—Use of protease inhibitors was associated with higher rates of liver aminotransferase elevations in patients with HIV; however, severe acute liver injury was uncommon with all antiretroviral therapy (ART) regimens, concluded a retrospective cohort study presented at IDWeek 2016.

“The risk of hepatotoxicity with modern ART remains unknown,” noted Charitha Gowda, MD, MPH, Division of Infectious Diseases, Nationwide Children’s Hospital, Columbus OH. “Evaluation of potential hepatotoxicity due to modern ART in clinical practice is important to ensure the safety of these medications in HIV-infected patients.”

Dr. Gowda and colleagues determined the absolute and comparative risks of acute liver injury associated with nucleos(t)ide reverse transcriptase inhibitor (NRTI) combinations, antiretroviral classes, and currently used ART, separately among those with and without viral hepatitis co-infection. Factors associated with acute liver injury were also determined.

The study included 10,083 patients who were HIV-positive and initiated ART in Kaiser Permanente Northern California (n=2,099) from 2004–2010 and the Veterans Aging Cohort Study (n=7,984) from 2004–2012. Databases from these two sources were merged for the study.

Dr. Gowda and colleagues determined occurrence of liver aminotransferases (AST or ALT) >200 U/L; severe acute liver injury, defined as an INR ≥1.5 plus a total bilirubin >2XULN within 30 days; and acute liver failure, ascertained among hepatitis-uninfected patients, defined as hospitalization with INR ≥1.5 plus hepatic encephalopathy or liver transplant.

Cox regression was used to determine hazard ratios (HRs) and 95% confidence intervals of end points among users of different NRTI backbones; protease inhibitor, integrase strand transfer inhibitors (INSTI), and non-NRTI classes; and currently used ART regimens. The most commonly prescribed drug or regimen was the reference.

They found that liver aminotransferases >200 U/L developed in 206 (2%) of patients within the first year of ART, occurring more frequently among those with HIV/viral hepatitis co-infected than HIV monoinfected persons (116.1 versus 20.7 events; P<0.001). Severe acute livery injury, however, was observed in less than 1% of patients, and no acute liver failure events were observed in patients who were not infected with viral hepatitis.

After adjusting for viral hepatitis and baseline aminotransferase, they found rate of liver aminotransferases >200 U/L to be higher for abacavir/lamivudine versus tenofovir/emtricitabine (TDF/FTC) for those who were HIV monoinfected (HR 1.19 [0.47–2.97]) compared with the co-infected group (HR 0.68 [0.29–1.57]).

Compared to non-NRTI users, adjusted rates of liver aminotransferases >200 U/L were similar to the reference regimen for initiators of a protease inhibitor for those who were HIV monoinfected (HR 0.87 [0.54–1.39]) but higher for those who were co-infected (HR 2.01 [1.36–2.96]).

For an INSTI-based regimen, the adjusted hazard ratios were 0.98 [0.13-7.22] for those with viral hepatitis co-infection and 1.98 [0.76–5.15] for those without viral hepatitis.

Initiators of raltegravir + TDF/FTC without viral hepatitis had higher rates of liver aminotransferases >200 U/L compared to efavirenz + TDF/FTC initiators, while initiators of boosted lopinavir + 3TC/ZDV, boosted darunavir + TDF/FTC, and boosted atazanavir + TDF/FTC all had higher rates than the reference among patients without hepatitis co-infection.

“These results support the hepatic safety of modern ART regimens,” the study authors concluded.