Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era

BACKGROUND: As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era. METHODS: Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE. RESULTS: Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28–1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270–2.395), non–nucleoside reverse transcriptase inhibitor–based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378–3.616), being cART naïve (HR, 6.046; 95% CI, 3.686–9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651–16.164). African American race (HR, 0.669; 95% CI, 0.510–0.877) and integrase strand transfer inhibitor (INSTI)–based cART (HR, 0.222; 95% CI, 0.104–0.474) were protective. CONCLUSIONS: Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.