Rapid virological response at week 4 predicts response to pegylated interferon plus ribavirin among HIV/HCV-coinfected patients.

INTRODUCTION: The clinical applicability of early viral kinetics at week 4 in predicting sustained virological response (SVR) of pegylated interferon (peg-IFN) plus ribavirin (RBV) in HIV/HCV-coinfected patients is unclear. Our objective was to determine if rapid virological response (RVR) at week 4 of therapy with peg-IFN and RBV could predict SVR among HIV/HCV-coinfected patients. METHODS: HIV/HCV-coinfected patients in whom an HCV viral load determination had been carried out at week 4 of therapy were included in the study. The positive predictive value (PPV) and the negative predictive value (NPV) of RVR (undetectable serum HCV RNA at 4 week) for SVR were calculated in the study population. Receiver operating characteristic curves were calculated to determine the best cutoff of HCV RNA decrease to predict treatment failure. RESULTS: A total of 101 HIV/HCV-coinfected patients were included. RVR and SVR were observed in 39 (39%) and in 49 (48%) individuals, respectively. Of patients with RVR, 37/39 patients achieved SVR (PPV: 95%), whereas 50/62 individuals without RVR did not show SVR (NPV: 81%). The highest NPV (96%) was reached by using a cutoff level of HCV RNA decrease of 0.6 log10. By applying this cutoff level, treatment could have been discontinued in 25 (25%) patients. CONCLUSIONS: An undetectable serum HCV RNA determination at week 4 of treatment with peg-IFN plus RBV is a reliable predictor of SVR in HIV/HCV-coinfected patients. In addition, a decrease of HCV RNA less than 0.6 log10 at this point of treatment could identify an appreciable proportion of individuals who will fail to achieve SVR.

Predictors of severe haematological toxicity secondary to pegylated interferon plus ribavirin treatment in HIV-HCV-coinfected patients.

BACKGROUND: Haematological adverse events related to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy could affect the patients' quality of life; however, the risk factors for severe haematological toxicity associated with this therapy in patients coinfected with hepatitis C virus (HCV) and HIV are unclear. The objective of this study was to identify predictors of severe haematological toxicity among HIV-HCV-coinfected patients treated with PEG-IFN plus RBV. METHODS: This retrospective multicentric study included 237 HIV-HCV-coinfected patients on PEG-IFN plus RBV. Predictors of severe anaemia, neutropenia, thrombocytopenia and overall haematological toxicity were analyzed. RESULTS: Eighty (34%) individuals showed an episode of severe haematological toxicity. Severe anaemia, neutropenia and thrombocytopenia occurred in 32 (13%), 42 (18%) and 26 (11%) patients, respectively. In the multivariate analysis, zidovudine use (adjusted odds ratio [AOR] 3.3; 95% confidence interval [CI] 1.6-10; P = 0.001), baseline body weight < 65 kg (AOR 2.5; 95% CI 1.1-5; P = 0.024), cirrhosis (AOR 5; 95% CI 1.6-16.6; P = 0.006), PEG-IFN-alpha2a (AOR 2.7; 95% CI 1.1-6.6; P = 0.029) and pretreatment haemoglobin level < 14 g/dl (AOR 2.7; 95% CI 1.3-5.5; P = 0.005) were associated with any kind of severe haematological toxicity. Likewise, haemoglobin level < 13 g/dl, neutrophil counts < 2,500 cells/mm3 and platelet counts < 175,000 cells/mm3 were independent predictors of severe anaemia, neutropenia and thrombocytopenia, respectively. CONCLUSIONS: Zidovudine treatment, cirrhosis, baseline low body weight, use of PEG-IFN-alpha2a, and baseline haemoglobin level < 14 g/dl are predictors of overall severe haematological toxicity secondary to PEG-IFN plus RBV in HIV-infected individuals. Low pretreatment levels of each haematological series predict a significant decrease of their values during therapy.

Incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among HIV-infected patients with chronic hepatitis C.

OBJECTIVES: To determine the incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients with known stage of liver fibrosis. METHODS: All HIV/HCV-coinfected patients were monitored for a period of 12 months after starting nelfinavir-containing regimens and, with an available liver biopsy, were included in a retrospective study. RESULTS: A total of 82 patients were included in the study. Nine (10.9%) HIV/HCV-coinfected patients showed an episode of severe hepatotoxicity during the study period. Eight (9.8%) individuals showed grade 3 or 4 change in levels of serum alanine aminotransferase and one subject presented with an event of decompensated liver cirrhosis. Six (18.2%) of 33 patients with advanced liver fibrosis and three (6%) of 49 individuals without advanced liver fibrosis showed an episode of severe hepatotoxicity (P = 0.1). In the multivariate analysis, only nevirapine use during nelfinavir therapy [adjusted odds ratio (AOR) 8.9; 95% confidence interval (CI), 1.4-54.1; P = 0.01] was independently associated with risk of development of severe liver toxicity. CONCLUSIONS: The incidence of severe hepatotoxicity of nelfinavir-containing regimens is low among HIV/HCV-coinfected patients with known stage of liver fibrosis. In addition, our findings show that concomitant nevirapine use is associated with an increased risk of severe hepatotoxicity in these subjects. Likewise, the proportion of severe liver toxicity tended to be higher in individuals with advanced liver fibrosis.

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.