Background: Nevirapine-containing regimens have been associated with a risk of significant elevations of liver transaminase levels. Higher risk in antiretroviral-naive populations has been related to gender and CD4+ T-cell count (women with CD4+ T-cell counts of ≥250/mm3 or men with CD4+ T-cell counts of ≥400/mm3, i.e. group at risk). However, recent studies do not confirm this association in HIV populations comprising patients who are antiretroviral-experienced. Moreover, the predictive value of gender and CD4+ T-cell count on the risk of raised transaminase levels has been poorly investigated in populations of patients co-infected with hepatitis C virus (HCV). Methods: Analysis of HIV-positive patients receiving nevirapine- containing regimens for the first time was conducted. Grade ≥III hepatotoxicity (i.e. ≥5 × upper limit of normal in alanine aminotranferase or aspartate aminotransferase levels) was the primary endpoint. Univariate and multivariable Cox proportional hazard regression models were separately conducted among HCV-antibody (Ab)-positive and HCV-Ab-negative patients. Results: Amongst 905 patients, 49% were HCV-Ab-positive and 79% were antiretroviral-experienced. Grade ≥III liver transaminase elevations developed in 7.1% of patients, accounting for an incidence of 2.47 (95% CI 1.97, 3.09) per 100 patient-years of follow-up. HCV-Ab reactivity was associated with a 3-fold increase in risk of developing relevant liver transaminase elevations (95% CI 1.75, 5.3; p < 0.001), whereas gender and CD4+ T-cell count did not impact significantly. When analysis was performed in HCV-Ab-negative patients, the outcome was independently correlated with the group at risk (hazard ratio [HR] 3.66; 95% CI 1.20, 11.14; p = 0.022). By contrast, in HCV-Ab-positive patients, the group at risk was not significantly associated with the outcome. Conclusions: Most of the excess rates of relevant raised transaminase levels in patients prescribed nevirapine-containing regimens could be attributed to HCV co-infection. Gender and CD4+ T-cell count appeared to have a statistically significant impact on the risk of relevant transaminase level elevations in HCV-negative, but not in HCV-positive patients, probably due to a diluting effect of HCV. Incidence of hepatic events after nevirapine-containing regimens did not appear to be a major concern in our cohort of patients who were mainly antiretroviral-experienced and negative for HCV-Ab. Preferably, nevirapine should be avoided in HCV co-infected patients and in males with CD4+ T-cell counts of ≥400/mm3 or females with CD4+ T-cell counts of ≥250/mm3. © 2007 Adis Data Information BV. All rights reserved.

Torti, C., Costarelli, S., De Silvestri, A., Quiros-Roldan, E., Lapadula, G., Cologni, G., et al. (2007). Analysis of severe hepatic events associated with nevirapine-containing regimens: CD4+ T-cell count and gender in hepatitis C seropositive and seronegative patients. DRUG SAFETY, 30(12), 1161-1169 [10.2165/00002018-200730120-00008].

Analysis of severe hepatic events associated with nevirapine-containing regimens: CD4+ T-cell count and gender in hepatitis C seropositive and seronegative patients

Lapadula G.;Puoti M.;
2007

Abstract

Background: Nevirapine-containing regimens have been associated with a risk of significant elevations of liver transaminase levels. Higher risk in antiretroviral-naive populations has been related to gender and CD4+ T-cell count (women with CD4+ T-cell counts of ≥250/mm3 or men with CD4+ T-cell counts of ≥400/mm3, i.e. group at risk). However, recent studies do not confirm this association in HIV populations comprising patients who are antiretroviral-experienced. Moreover, the predictive value of gender and CD4+ T-cell count on the risk of raised transaminase levels has been poorly investigated in populations of patients co-infected with hepatitis C virus (HCV). Methods: Analysis of HIV-positive patients receiving nevirapine- containing regimens for the first time was conducted. Grade ≥III hepatotoxicity (i.e. ≥5 × upper limit of normal in alanine aminotranferase or aspartate aminotransferase levels) was the primary endpoint. Univariate and multivariable Cox proportional hazard regression models were separately conducted among HCV-antibody (Ab)-positive and HCV-Ab-negative patients. Results: Amongst 905 patients, 49% were HCV-Ab-positive and 79% were antiretroviral-experienced. Grade ≥III liver transaminase elevations developed in 7.1% of patients, accounting for an incidence of 2.47 (95% CI 1.97, 3.09) per 100 patient-years of follow-up. HCV-Ab reactivity was associated with a 3-fold increase in risk of developing relevant liver transaminase elevations (95% CI 1.75, 5.3; p < 0.001), whereas gender and CD4+ T-cell count did not impact significantly. When analysis was performed in HCV-Ab-negative patients, the outcome was independently correlated with the group at risk (hazard ratio [HR] 3.66; 95% CI 1.20, 11.14; p = 0.022). By contrast, in HCV-Ab-positive patients, the group at risk was not significantly associated with the outcome. Conclusions: Most of the excess rates of relevant raised transaminase levels in patients prescribed nevirapine-containing regimens could be attributed to HCV co-infection. Gender and CD4+ T-cell count appeared to have a statistically significant impact on the risk of relevant transaminase level elevations in HCV-negative, but not in HCV-positive patients, probably due to a diluting effect of HCV. Incidence of hepatic events after nevirapine-containing regimens did not appear to be a major concern in our cohort of patients who were mainly antiretroviral-experienced and negative for HCV-Ab. Preferably, nevirapine should be avoided in HCV co-infected patients and in males with CD4+ T-cell counts of ≥400/mm3 or females with CD4+ T-cell counts of ≥250/mm3. © 2007 Adis Data Information BV. All rights reserved.
Articolo in rivista - Articolo scientifico
Antiretrovirals, adverse reactions; Antiretrovirals, therapeutic use; Hepatitis C, general; Liver disorders, drug induced; Liver dysfunction, drug induced; Nevirapine, adverse reactions; Nevirapine, therapeutic use; Adult; Alanine Transaminase; Anti-HIV Agents; Aspartate Aminotransferases; CD4 Lymphocyte Count; Chemical and Drug Induced Liver Injury; Cohort Studies; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; Humans; Liver; Liver Function Tests; Male; Nevirapine; Retrospective Studies; Reverse Transcriptase Inhibitors; Risk Factors; Sex Factors
English
2007
30
12
1161
1169
none
Torti, C., Costarelli, S., De Silvestri, A., Quiros-Roldan, E., Lapadula, G., Cologni, G., et al. (2007). Analysis of severe hepatic events associated with nevirapine-containing regimens: CD4+ T-cell count and gender in hepatitis C seropositive and seronegative patients. DRUG SAFETY, 30(12), 1161-1169 [10.2165/00002018-200730120-00008].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/326124
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