Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients

Neukam, Karin; Mira, José A.; Ruíz-Morales, Josefa; Rivero, Antonio; Collado, Antonio; Torres-Cornejo, Almudena; Merino, Dolores; Santos-Gil, Ignacio de los; Macı́as, Juan; González-Serrano, Mercedes; Camacho, Ángela; Parra-García, Ginés David; Pineda, Juan A.; Rivero‐Juárez, Antonio; Pérez-Camacho, Inés; Torre‐Cisneros, Julián; Aliaga-Jiménez, Angelina; López‐Cortés, Luis F.; Palacios-Muñoz, Rosario; Santos-González, Jesús; Márquez‐Solero, Manuel; Nuño-Álvarez, Enrique; Fernández, Andrea

doi:10.1093/jac/dkr357

Cited by 25 publications

(28 citation statements)

References 19 publications

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“…The observed cholestasis liver injury was more of transient and mild. The low severity grade of efavirenz based HAART is accordance with other reports [35]. Though mild in most patients, efavirenz based HAART induced liver injury can be life threatening in susceptible individuals [13].…”

Section: Discussionsupporting

confidence: 90%

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

et al. 2014

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ObjectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).MethodsA total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model.ResultsA total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART.ConclusionHAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI.

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Section: Discussionsupporting

confidence: 90%

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

et al. 2014

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“…assessed the frequency of severe LEEs among 76 Spanish patients initiating an efavirenz-containing regimen and 186 initiating a boosted PI. (24) There was no difference in the proportion developing grade 3–4 LEEs between the two groups (efavirenz, 6.6%; boosted PI, 8.1%, P=0.681). Indeed, in two recent reviews of the hepatotoxicity of ARVs among all HIV-infected patients (25) and among HIV/HCV-coinfected individuals (26), the hepatic safety profile of newer agents appears significantly improved compared to agents used in the late 1990s and early 2000s.…”

Section: Discussionmentioning

confidence: 79%

Hepatic Safety and Tolerability of Raltegravir among HIV Patients Coinfected with Hepatitis B And/Or C

et al. 2013

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Background Potential liver toxicity is an important consideration for antiretroviral selection among patients coinfected with HIV and viral hepatitis (B and/or C). We sought to describe the hepatic safety profile of raltegravir in this population. Methods Using data from HIV clinical cohorts at Johns Hopkins University and the University of North Carolina at Chapel Hill, we evaluated factors associated with liver enzyme elevations (LEEs) and calculated adverse event incidence rates for patients initiated on raltegravir-containing regimens prior to January 1, 2010. LEEs were graded according to Division of AIDS definitions. Results During the study period, 456 patients received raltegravir – of whom 36% were hepatitis-coinfected (138 HCV, 17 HBV, 11 HBV+HCV). Coinfected patients were more likely to have baseline abnormal LEEs, and developed severe (grade 3–4) LEEs at a rate 3.4 times that of HIV-monoinfected patients (95% confidence interval (CI), 1.28, 9.61). Among all participants, the incidence rate for first occurrence of severe LEEs was 5 per 100 person-years (95% CI, 3, 7). In adjusted analyses, coinfected patients had a 2.7-fold increased hazard of severe LEEs (95% CI, 1.03, 7.04). Sixty percent of severe abnormalities occurred within 6 months after starting raltegravir; the drug was discontinued in 3 coinfected patients (1.3%) and 18 monoinfected patients (6.2%). Conclusions Compared to HIV-monoinfected patients, those with HIV-hepatitis coinfection are at increased hazard of developing LEEs on raltegravir, at a level similar to other antiretrovirals. Severe events were uncommon, rarely leading to raltegravir discontinuation. With appropriate monitoring, raltegravir-based therapy is safe in hepatitis-coinfected patients.

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“…Several other studies also reported the same conclusion. 19e22 Neukam et al 19 and Pineda et al 21,22 found no association between underlying advanced liver fibrosis and occurrence of TE in different HAART regimens, including NNRTI and boosted PI. Prospective studies with longer follow-up periods and a larger population size should be conducted to confirm the relationship between liver fibrosis and TE frequency in HIV and HCV co-infected patients.…”

Section: Discussionmentioning

confidence: 99%

Highly active antiretroviral therapy-related hepatotoxicity in human immunodeficiency virus and hepatitis C virus co-infected patients with advanced liver fibrosis in Taiwan

Chou

Tsai

et al. 2016

Journal of Microbiology, Immunology and Infection

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Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients

Cited by 25 publications

References 19 publications

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

Hepatic Safety and Tolerability of Raltegravir among HIV Patients Coinfected with Hepatitis B And/Or C

Highly active antiretroviral therapy-related hepatotoxicity in human immunodeficiency virus and hepatitis C virus co-infected patients with advanced liver fibrosis in Taiwan

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