abacavir and Liver-Cirrhosis

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients.

Topics: Adenine; Anti-HIV Agents; Antiviral Agents; Coinfection; Deoxycytidine; Dideoxynucleosides; Disease Progression; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Emtricitabine; Hepatitis C, Chronic; HIV Infections; Homosexuality, Male; Humans; Interferon-alpha; Lamivudine; Liver Cirrhosis; Liver Diseases; Male; Oligopeptides; Organophosphonates; Polyethylene Glycols; Proline; Pyrrolidinones; Raltegravir Potassium; Recombinant Proteins; Ribavirin; Serine Proteinase Inhibitors; Substance Abuse, Intravenous; Tenofovir; Treatment Outcome

To compare plasma antiretroviral concentrations in HIV-HCV co-infected and in matched HIV mono-infected patients.. This was a cross-sectional, observational study. Antiretroviral trough concentrations (C(min)) in plasma were measured in HIV-HCV co-infected patients with liver disease documented by liver biopsy, matched with HIV mono-infected patients according to gender and antiretroviral treatment. C(min) values in serum were measured using an HPLC method. Statistical analysis was performed using the Wilcoxon test.. Seventy-three HIV-HCV co-infected patients and 66 HIV-infected patients were enrolled; 70% of patients were receiving a protease inhibitor (PI)- and 30% a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. Among the 73 co-infected patients, 27 had a fibrosis score (Fibrotest(®)) of F4. Abacavir was the only nucleoside reverse transcriptase inhibitor whose trough concentrations differed between the co-infected and mono-infected groups. PI median plasma C(min) values were not different in the two groups, except for lopinavir, with a lower C(min) in the co-infected group than in the HIV-infected group (median 3673 versus 5990 ng/mL, P=0.04), and nelfinavir, with significantly higher concentrations in the co-infected group. Seventy-five percent of co-infected patients scoring F4, 33% of those scoring F0-F3 and 12% of HIV-infected patients were underdosed (P=0.02). Co-infected patients receiving an NNRTI had a higher plasma C(min) than HIV-infected patients; median C(min) was 3583 versus 1494 ng/mL (P=0.025) and 5331 versus 3954 ng/mL (P=0.10) for efavirenz and nevirapine, respectively. Overall, there was a greater proportion of co-infected patients with high concentrations of both NNRTIs (15/23) compared with HIV mono-infected patients (5/21) (P=0.008), especially in co-infected patients with an advanced liver fibrosis stage.. Median plasma C(min) values differed significantly between HIV and HIV-HCV co-infected patients for abacavir, lopinavir and efavirenz. NNRTIs were strongly overdosed in HIV-HCV co-infected patients.

Topics: Adult; Aged; Alkynes; Anti-Retroviral Agents; Benzoxazines; Case-Control Studies; Chromatography, High Pressure Liquid; Cross-Sectional Studies; Cyclopropanes; Dideoxynucleosides; Female; Hepatitis C, Chronic; HIV Infections; Humans; Liver Cirrhosis; Lopinavir; Male; Middle Aged; Plasma; Pyrimidinones

Topics: Anti-Retroviral Agents; Dideoxynucleosides; Humans; Liver Cirrhosis