February 10, 2004
Multiple studies have shown that patients with HIV/hepatitis C (HCV) coinfection are at greater risk for liver toxicity from antiretroviral therapy. This is usually manifested as an increase in liver enzymes and, sometimes, HCV RNA levels. While the direct effect of HIV medications versus augmented immune response to HCV are often difficult to sort out, apparent hepatotoxicity after starting treatment is a common clinical problem. This abstract is an analysis of nelfinavir (NFV, Viracept)- and lopinavir/ritonavir (LPV/r, Kaletra)-treated patients with HIV/HCV from the Abbott 863 study, with particular attention paid to HCV RNA and alanine aminotransferase (ALT) levels.
A subset of 70 HCV-infected patients from the study were retrospectively evaluated. All patients received stavudine (d4T, Zerit) and lamivudine (3TC, Epivir) with randomization to either nelfinavir or lopinavir/ritonavir. At baseline, 57 of 70 patients (81%) were positive for HCV RNA, and 68% had genotype 1. There were no significant differences between the nelfinavir and the lopinavir/ritonavir arms in terms of baseline demographics, HIV-related clinical and laboratory characteristics, HCV RNA levels or ALT levels.
As has been reported in previous studies, the initiation of antiretroviral therapy was associated with a significant increase in HCV RNA levels. The increases were generally similar in both treatment arms, with the exception of the subgroup of patients with CD4 counts below 100 cells/mm3, for whom HCV RNA levels increased more in the nelfinavir than in the lopinavir/ritonavir arm. Although early in the study greater ALT increases occurred in the nelfinavir arm than the lopinavir/ritonavir arm, by week 48 the difference was not statistically significant. There were no patients who discontinued therapy due to liver toxicity. Importantly, both study arms had good CD4 count responses (234 cells/mm3 with lopinavir/ritonavir and 184 cells/mm3 with nelfinavir), contrary to some studies that have shown a lesser degree of immune reconstitution among HCV-infected patients.
This study supports the safety of both the lopinavir/ritonavir and the nelfinavir-based regimens in HCV-infected patients -- at least those who were stable enough to enroll in this treatment-naive study, which is encouraging. The increases in HCV RNA levels are of unclear clinical significance, especially given that no patient required cessation of therapy for liver-related issues.
While the results of this analysis are encouraging, a far more vexing problem for clinical practice is that of HIV/HCV coinfected patients with advanced liver disease, as they often tolerate any antiretroviral therapy very poorly. Further study of the predictors of antiretroviral-associated hepatotoxicity in this more tenuous group is warranted.
Abstract: Evaluation of HCV RNA and Liver Injury in HCV/HIV Co-Infected Patients Initiating Lopinavir/r or Nelfinavir-Based Therapy (Poster 811)
Authored by: K. E. Sherman, N. J. Shire, P. Cernohous, S. D. Rouster, B. Da Silva, J. Moseley, S. Brun
Affiliations: Univ. of Cincinnati, OH; Abbott Labs., Abbott Park, IL
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