Hepatic steatosis (HS) is a cause of liver disease. In addition, steatohepatitis can induce liver fibrosis and accelerate fibrosis progression associated with HCV. As a consequence, the effects of antiretroviral drugs less likely to induce increases in HS in HIV/HCV coinfection need to be investigated. Because of this, we aimed at comparing the impact of switching from efavirenz (EFV) plus two nucleoside analogs (nucs) to rategravir (RAL) plus two nucs versus continuing with EFV plus two nucs on HS among HIV/HCV-coinfected patients.
This was a phase IV, open-label, randomized clinical trial (ClinicalTrials.gov: NCT01900015). HIV-infected patients, with or without detectable plasma HCV RNA, on current EFV plus two nucs were randomized 1:1 to switch EFV to RAL (400 mg BID), maintaining nucs unchanged, or to continue with EFV plus two nucs. At baseline (BL), eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m, i.e. significant HS. Changes in HS were measured using CAP at BL, 24 and 48 weeks of follow-up.
In this interim analysis, 37 patients, 19 subjects randomized to RAL and 18 to EFV, have reached 48 weeks of follow-up. The proportion of men for RAL vs. EFV groups at BL were 90% vs. 83% (p=0.939). BL HCV RNA was detectable in 74% individuals switched to RAL vs. 67% subjects continuing on EFV (p=0.874). HIV viral load was undetectable at BL in 100% for the RAL group and 94% for the EFV group (p=0.515). The BL median (Q1-Q3) values for RAL vs. EFV group were: Age, 52 (45-55) vs. 48 (47-52) years (p=0.233); body mass index, 27 (23.9-29.5) vs. 25 (23.7-26.6) Kg/m2 (p=0.503); CD4 counts, 556 (342-856) vs. 582 (371-774) cells/mcL (p=0.684); HOMA, 2.4 (1.8-4) vs. 2.2 (1.8-5.4) (p=0.949); CAP, 273 (246-303) vs. 258 (247-287) dB/m (p=0.374); liver stiffness, 6.6 (5.3-10.9) vs. 6.7 (3.8-8.4) KPa (p=0.391). The median (Q1-Q3) of the difference in CAP values between baseline and 48 weeks (∆CAP) was -20 (-67, 15) dB/m for the RAL group and 28.5 (-18.8, 47.8) dB/m for the EFV group (p=0.019). The proportion of patients with CAP <238 dB/m at 48 weeks was 9 (47%) for the RAL arm vs. 3 (17%) for the EFV arm (p=0.049).
After 48 weeks, HIV-infected individuals switching from EFV to RAL showed decreases in the degree of HS, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant HS after 48 weeks was greater for those who switched from EFV to RAL.