Liver tolerance of raltegravir-containing antiretroviral therapy in HIV-infected patients with chronic hepatitis C

Macı́as, Juan; Neukam, Karin; Portilla, Joaquín; Iribarren, José Antonio; Santos, Ignacio; Rivero, Antonio; Márquez, Manuel; Delgado, Marcial; Téllez, Francisco; Merino, Dolores; Giner, Livia; Wichmann, Miguel Ángel von; Pineda, Juan A.

doi:10.1093/jac/dkr083

Cited by 19 publications

(12 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another study from Spain, Macías et al used retrospective cohort data to examine severe LEEs among 108 HIV/HCV coinfected patients during their first 12 months of raltegravir exposure. (15) Ten patients developed grade 3–4 transaminase abnormalities, but no patients discontinued raltegravir due to hepatoxic events, leading the authors to conclude that raltegravir is safe in this population. Finally, Weimer et al examined data from a nationwide observational study of raltegravir recipients in Italy to study the impact of HBV or HCV coinfection on responses to “salvage” ARV regimens.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 98%

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

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Morbidity and mortality related to transplantation included reports of serious AE (SAE) and documentation of graft failure, veno-occlusive disease (VOD), sepsis or bacterial infections, noninfectious pneumonia, hemorrhage, refractory GVHD, and multisystem organ failure. Nonfatal toxicity included any SAE or documentation of grade IV ALT, AST, or bilirubin elevation [23,24], grade III serum creatinine elevation [25], reversible VOD, hemorrhagic cystitis, pericardial effusion, or subdural hematoma.…”

Section: Non-apocell Related Toxicity and Non-relapse Mortality (Nrm)mentioning

confidence: 99%

Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I/IIa Clinical Trial

Mevorach

Zuckerman

Reiner

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Because of its potent immunomodulatory effect, an infusion of donor mononuclear early apoptotic cells (ApoCell) was tested in addition to cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease (GVHD) after HLA-matched myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor. In a phase I/IIa clinical trial, we treated 13 patients (median age, 37 years; range, 20 to 59 years) with hematologic malignancies: 7 patients with acute lymphoblastic leukemia, 5 patients with acute myeloid leukemia, and 1 patient with chronic myeloid leukemia, who received conventional myeloablative conditioning, with 35, 70, 140, or 210 × 10(6) cell/kg of donor ApoCell, on day -1 of transplantation. Engraftment was successful in all patients with median time to neutrophil recovery of 13 days (range, 11 to 19), and platelet recovery of 15 days (range, 11 to 59). Serious adverse effects were reported on 10 occasions in the trial, all of which were considered unrelated (n = 7) or unlikely to be related (n = 3) to ApoCell infusion. The nonrelapse mortality at day 100 and 180 after transplantation was 7.7% and the overall survival at 100 and 180 days after transplantation was 92% and 85%, respectively. All ApoCell preparations showed an in vitro significant tolerogenic effect upon interaction with dendritic cells. The overall incidence of acute grades II to IV GVHD was 23%, whereas among those receiving the 2 higher doses (n = 6), the rate was 0%. These results suggest that a single infusion of donor ApoCell in HLA-matched allogeneic HSCT is a safe and potentially effective prophylaxis for acute GVHD occurring after myeloablative conditioning. No dose limiting toxicity was observed. (Clinicaltrials.gov no. NCT00524784).

show abstract

“…46 Lower rates of DILI have been observed with the more recent antivirals such as etravirine, raltegravir, and maraviroc. [47][48][49] Nonalcoholic Fatty Liver Disease and Alcohol-Induced Liver Disease…”

Section: Hepatocellular Carcinoma and Cirrhosismentioning

confidence: 99%

The Burden of Liver Disease in Human Immunodeficiency Virus-Infected Patients

et al. 2012

View full text Add to dashboard Cite

Introduction of effective combined antiretroviral therapy has made human immunodeficiency virus (HIV) infection a chronic illness. Substantial reductions in the number of acquired immunodeficiency syndrome- (AIDS-) related deaths have been accompanied by an increase in liver-related morbidity and mortality. Liver diseases rank in the first three most-common causes of death in HIV-infected persons. Mortality is mainly due to cirrhosis and hepatocellular carcinoma induced by hepatitis C virus and hepatitis B virus coinfection. However, antiretroviral drugs toxicity also plays a role. Nonalcoholic fatty liver disease is a common cause of liver injury as well. Nevertheless, alcohol consumption probably plays a pivotal role. Noncirrhotic portal hypertension, an uncommon condition observed in less than 1% of patients, is increasingly described. Finally, acute hepatitis A virus (HAV) and acute and even chronic hepatitis E virus infection have also been reported as causes of liver damage in HIV. Anti-HAV vaccination is thus recommended in persons at risk living with HIV.

show abstract

Liver tolerance of raltegravir-containing antiretroviral therapy in HIV-infected patients with chronic hepatitis C

Cited by 19 publications

References 7 publications

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

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

Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I/IIa Clinical Trial

The Burden of Liver Disease in Human Immunodeficiency Virus-Infected Patients

Contact Info

Product

Resources

About