
Methods: We conducted a cohort study in 10,083 HIV+ persons initiating ART in Kaiser Permanente Northern California (n=2,099) from 2004-2010 and the Veterans Aging Cohort Study (n=7,984) from 2004-2012. Within the first year of ART, we determined occurrence of: 1) liver aminotransferases >200 U/L, and 2) severe ALI (coagulopathy and jaundice within 30 days of each other). We used Cox regression to determine hazard ratios (HRs) and 95% confidence intervals of endpoints among users of: 1) different nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbones, 2) protease inhibitor (PI), integrase strand transfer inhibitors (INSTI), and non-NRTI classes, and 3) currently used ART regimens. The most commonly prescribed drug or regimen was the reference.
Results: After adjustment for viral hepatitis and baseline aminotransferase, the rate of liver aminotransferases >200 U/L was similar for abacavir/lamivudine versus tenofovir/emtricitabine (TDF/FTC; HR, 0.86 [0.56-1.60]). Compared to non-NRTI users, adjusted rates of liver aminotransferases >200 U/L were higher for initiators of a PI (HR, 1.39 [1.04-1.86]) or INSTI-based regimen (HR, 1.81 [0.77-4.22]), though the latter comparison did not reach statistical significance. Rates of liver aminotransferases >200 U/L were higher for initiators of raltegravir+TDF/FTC (HR, 2.00; [0.85-4.72]), atazanavir+TDF/FTC (HR, 1.48 [0.95-2.30]), and darunavir +TDF/FTC (HR, 1.42 [0.60-3.38] compared to efavirenz+TDF/FTC initiators but were not statistically significant. Severe ALI was too rare to evaluate in adjusted analyses.
Conclusion: PI use was associated with higher rates of liver aminotransferase elevations, but severe ALI was uncommon with all regimens.

C. Gowda,
None
Q. Liu, None
D. M. Carbonari, None
J. D. Lewis, Centocor: Grant Investigator , Research grant
Amgen: Consultant , Consulting fee
Millennium Pharmaceuticals: Consultant , Consulting fee
Pfizer: Consultant , Consulting fee
K. Forde, None
D. S. Goldberg, None
K. R. Reddy, Abbott: Grant Investigator , Research grant
Anadys: Grant Investigator , Research grant
Bristol-Myers Squibb: Consultant and Grant Investigator , Consulting fee and Research grant
Genetech-Roche: Consultant and Grant Investigator , Consulting fee and Research grant
Gilead Sciences: Consultant and Grant Investigator , Consulting fee and Research grant
Merck: Consultant and Grant Investigator , Consulting fee and Research grant
Ikaria: Grant Investigator , Research grant
Janssen: Consultant and Grant Investigator , Consulting fee and Research grant
Vertex: Consultant and Grant Investigator , Consulting fee and Research grant
Idenix: Consultant , Consulting fee
American Liver Foundation: Scientific Advisor , Consulting fee
ViralEd: Development of educational materials , Speaker honorarium
J. Roy, None
A. R. Marks, None
J. L. Schneider, None
J. R. Kostman, Gilead Sciences: Scientific Advisor , Consulting fee
D. Corley, Pfizer: Grant Investigator , Research grant
J. P. Tate, None
A. C. Justice, None
V. Lo Re III, AstraZeneca: Grant Investigator , Research grant
Gilead Sciences: Grant Investigator , Research grant