Original articleHepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish GroupSeguridad hepática de maraviroc en pacienes coinfectados con VIH y hepatitis C y/o B. Grupo español de la cohorte de Maraviroc
Introduction
Approximately 1–8% of HIV-infected patients develop severe hepatitis, mostly grade 3 or 4 elevations in aminotransferases, during the first year of antiretroviral therapy (ART).1 Coinfection with either hepatitis B (HBV) or hepatitis C (HCV) has been frequently reported as a major risk factor for liver toxicity after initiation of ART.1
Although the incidence of severe liver toxicity is lower with currently recommended regimens, and the majority of cases involve asymptomatic liver enzyme elevations2, 3, 4, 5 some cases of severe liver disease have been still reported3 and ART-related hepatotoxicity is a concern in the management of HIV-infected subjects, mainly in those coinfected with HCV and/or HBV.
Initial concerns were raised in regard with the hepatic safety of CCR5 antagonists, following the description of severe cases of hepatotoxicity with aplaviroc.6 Maraviroc (MRV), the first and only CCR5 antagonist approved so far for ART, has shown a favorable safety profile both in patients enrolled in clinical trials and in the expanded access program.7 However, very limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HCV and/or HBV,8 and the package insert for maraviroc includes some specific warnings in regard with the potential risk of hepatotoxicity.9
On the other hand, development of progressive liver disease is one of the principal comorbidities in HIV infected patients coinfected with HCV and/or HBV, and complications associated to end-stage liver disease remain a major cause of morbidity and mortality among coinfected patients.10 In chronic hepatitis, the CCR5/RANTES pathway appears to be involved in the inflammatory response, a critical step in the promotion of hepatic fibrosis, metabolic liver disease and the development of hepatocellular carcinoma.11
Preclinical data, obtained from different animal models of liver injury, have shown that blocking the CCR5 activation pathway could play a protective role on liver fibrosis progression12, 13 hepatocellular carcinoma development,14, 15 and in protecting against the development of non-alcoholic fatty liver disease (NAFLD).16
The primary outcome of this substudy was to compare the liver safety profile of maraviroc-containing ART in a large heterogeneous cohort of patients coinfected or not with HBV and/or HCV, in real-life conditions. As a secondary outcome we studied the impact of maraviroc treatment on liver fibrosis progression by analyzing changes in FIB-4 index over time.
Section snippets
Study design and follow-up
Demographic and clinical data from all maraviroc-treated subjects in 27 centers across Spain were retrospectively collected in an observational multicenter cohort study. Complete study design and data on efficacy and overall safety have been reported elsewhere.17 Briefly, all HIV-1 infected adults receiving a first dose of maraviroc and with at least one follow-up visit were recruited. Data obtained from every 3–6 months scheduled visits until the last follow-up control were entered into a web
Patient characteristics
Baseline characteristics of 667 patients analyzed are summarized in Table 1. Of them, 313 (46.9%) were co-infected either with HCV (n = 282; 42.2%) or HBV (n = 14; 2.1%) or both HBV and HCV (n = 17; 2.5%). Median age was 45 years; 74% were men; main route of infection was IDU (80.5%) in coinfected and sexual intercourse (84.8%) in HIV-monoinfected patients. Salvage therapy was the indication for the maraviroc-containing regimen in more than half of patients in both groups. Maraviroc dose ranged from
Discussion
In the present study, including more than 300 patients coinfected with HCV and/or HBV, only 2 patients (0.3%) discontinued maraviroc because of severe hepatitis. In regard with the impact of HCV or HBV coinfection on the risk of hepatitis, the incidence of grade 3–4 hypertransaminasemia, was 5-fold higher in coinfected patients. Notwithstanding, the relative risk in coinfected patients was inferior to 2-fold in the analysis adjusted by baseline levels, when defining grade 3–4 as ASLT/ALT
Conflict of interest
The authors declare no conflicts of interest.
Acknowledgment
ViiV Healthcare supported the study with an unrestricted grant.
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Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection
2018, Enfermedades Infecciosas y Microbiologia Clinica