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Background:  Initiation of highly active antiretroviral therapy (HAART) in HCV/HIV-co-infected patients has been associated with increased HCV viral load and transaminase flares. Prior studies have included mixed treatment regimens, making interpretation difficult. This study compared 2 HAART regimens in naïve subjects.

Methods:  We identified 70 putatively co-infected patients (HCV EIA-positive) from a phase 3 trial in which antiretroviral naïve patients were randomized to receive either lopinavir (LPV)/r 400/100 mg twice daily or nelfinavir (NFV) 750 mg 3 times daily, both dosed with stavudine and lamivudine, were retrospectively evaluated. HCV and HIV RNA viral load (Roche Amplicor Monitor) were measured at baseline, weeks 24/48, and during ALT increases to >5x the upper limit of normal.

Results:  Of 70 patients, 57 (81%) were positive for HCV RNA at baseline. Six pts in each treatment arm discontinued the study prior to week 48. Among this subset of patients reaching 48 weeks of therapy, HIV virologic/immunologic responses were grossly similar. Mean baseline HCV viral load was 6.07 and 6.22 log₁₀ IU/mL in LPV/r (n = 22) and NFV (n = 35) groups, respectively (p = 0.607). HCV RNA tended to increase to a mean of 6.68/6.32 log₁₀ IU/mL and 6.48 /6.44 log₁₀ IU/mL for the LPV/r and NFV groups, respectively, at weeks 24/48. In patients with baseline CD₄ <100 cells/mm³, a higher proportion of pts in the NFV group vs LPV/r group experienced a >0.5 log increase in HCV viral load from baseline to week 48 (5/11 [45%] vs 0/10, respectively, p = 0.035). CD₄ and HCV genotype were not associated with HCV viral load changes at 48 weeks in either treatment group. Mean ALT at baseline was 55 U/mL for the LPV/r group and 47 U/mL for the NFV group. There were mean increases in ALT of 38 U/mL and 16 U/mL for the NFV group vs decreases of 14 U/mL and 11 U/mL for the LPV/r group at week 24 (p = 0.006) and week 48 (p = 0.101), respectively.

Conclusions:  In HAART-naïve HCV/HIV-co-infected patients, initiation of LPV/r or NFV-based therapy tends to result in increased serum HCV RNA at 24 weeks that improves by 48 weeks of therapy, with significantly more >0.5 log₁₀ increases from baseline to week 48 in NFV-treated patients with baseline CD₄ <100 cells/mm³. An increase was observed in mean ALT levels in the NFV arm at week 24, but not in the LPV/r-treated group, although week 48 ALT values were not significantly different from baseline in either group. These observations may have clinical relevance in terms of interpretation of ALT abnormalities following initiation of HAART in co-infected patients.

Keywords: Lopinavir; HCV; liver injury