Influence of genotype 3 hepatitis C coinfection on liver enzyme elevation in HIV-1 - Positive patients after commencement of a new highly active Antiretroviral regimen - Results from the EPOKA-MASTER cohort
ABSTRACT The independent role of hepatitis C virus (HCV) genotype 3 in liver transaminase elevation following highly active antiretroviral regimens is still controversial.
Analysis of data from a cohort of 492 HIV/HCV-coinfected patients was conducted using an intention-to-treat approach. Incidence of grade > or = III liver transaminase elevation was estimated per 100 patient-years of follow-up. Univariate and multiple proportional hazards regression analysis of factors that may predict liver enzyme elevation was performed.
The incidence of grade > or = III hepatotoxicity was 25 per 100 patient-years among patients coinfected with HCV genotype 3 and 11 per 100 patient-years among those with other genotypes. On multiple proportional hazard regression analysis, time-to-grade > or = III liver enzyme elevation was directly correlated with HCV genotype 3 (hazards ratio [HR]: 2.0, 95% CI: 1.3 to 2.9; P = 0.001), male gender (HR: 2.7; 95% CI: 1.3 to 5.7; P = 0.007), chronic hepatitis B virus infection (HR: 2.9, 95% CI: 1.5 to 5.9; P = 0.002), and alanine aminotransferase level at baseline (per 10 IU/L HR: 1.10; 95% CI: 1.06 to 1.15; P < 0.001). In the same model, higher CD4 T-cell counts at baseline were inversely correlated with risk of hepatotoxicity (HR: 0.998; 95% CI: 0.997 to 0.999; P = 0.036). Moreover, among patients experienced to antiretroviral drugs, previous grade > or = III hepatotoxicity (HR: 2.8; 95% CI: 1.8 to 4.3; P < 0.001) was an adjunctive independent risk factor.
HIV-positive patients coinfected with HCV genotype 3 displayed a higher risk of relevant hepatotoxicity, independently from other clinical variables. The impact of HCV genotype outweighed the role of drugs in determining hepatotoxicity.
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ABSTRACT: Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV, and is responsible for a heavy burden of morbidity and mortality. HIV-HCV management is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens. To develop national standards for the management of HCV-HIV coinfected adults in the Canadian context. A panel with specific clinical expertise in HIV-HCV co-infection was convened by The CIHR HIV Trials Network to review current literature, existing guidelines and protocols. Following broad solicitation for input, consensus recommendations were approved by the working group, and were characterized using a Class (benefit verses harm) and Level (strength of certainty) quality-of-evidence scale. All HIV-HCV coinfected individuals should be assessed for HCV therapy. Individuals unable to initiate HCV therapy should initiate antiretroviral therapy to slow liver disease progression. Standard of care for genotype 1 is pegylated interferon and weight-based ribavirin dosing plus an HCV protease inhibitor; traditional dual therapy for 24 weeks (for genotype 2/3 with virological clearance at week 4); or 48 weeks (for genotypes 2-6). Therapy deferral for individuals with mild liver disease may be considered. HIV should not be considered a barrier to liver transplantation in coinfected patients. Recommendations may not supersede individual clinical judgement.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 01/2013; 24(4):217-38. · 0.49 Impact Factor
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ABSTRACT: Raltegravir is a switch option for HIV/HCV co-infected individuals due to its hepatic neutral profile. We evaluated the effect of a switch to Raltegravir from other antiretroviral agents in HIV and HCV-co-infected individuals naïve to HCV therapy. Observational, single-centre study. Data on alanine aminotransferase levels, HCV-VL, CD4 cell count, HIV viral load levels and hepatic fibrosis score were collated six months pre-switch, at the time of switch and six months post-switch to raltegravir therapy. Results were compared utilizing the Kruskal-Wallis test. Twenty-seven individuals were identified. Median age was 43 years, median duration of HIV infection 7 years and median documented period of HCV infection at the time of switch 26 months. A sustained improvement in ALT levels was observed. Median ALT levels were 254 IU/L at the time of switch, decreasing significantly to 176 IU/L, (p=0.0226) and 90 IU/L (p=0.0138) 1 month post switch and 6 months post switch respectively. The median Hepatitis C viral load level at the time of the switch was 341,783 copies/mL, which decreased to 224,066 copies/mL 6 months after switch (p = 0.04). A switch to Raltegravir in individuals with HIV/HCV co-infection was effective in maintaining HIV virological suppression with improvement in drug-associated hepatotoxicity as measured by ALT.The Journal of infection 05/2014; DOI:10.1016/j.jinf.2014.04.005 · 4.02 Impact Factor