ABSTRACT
Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LT(x). Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LT(x) was done. Blood trough concentrations (C(t)) of IS were obtained using a commercial MEIA test; plasma C(t) of PI(s) were measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma C(t) were observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LT(x) than when using unboosted PI(s). Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6-14) after resuming boosted PI(s) and 2.9 (range 2-4) after unboosted PI(s). The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PI(s) exhibited lesser PK interactions with IS than did RTV-boosted PI(s) and were thus more amenable to use in the post-LT(x) setting.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Adult , Chromatography, High Pressure Liquid , Cross-Sectional Studies , Dose-Response Relationship, Drug , Female , HIV Infections/surgery , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/blood , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle AgedABSTRACT
BACKGROUND: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLT(x)). PATIENTS AND METHODS: This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. RESULTS: Fifteen patients (ten males and five females, age range 36-59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 microl(-1), and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 microl(-1) , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). CONCLUSIONS: Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLT(x) in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Liver Failure/complications , Oligopeptides/therapeutic use , Pyridines/therapeutic use , Adult , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , Atazanavir Sulfate , CD4 Lymphocyte Count , Female , Follow-Up Studies , HIV Infections/immunology , Humans , Liver Failure/mortality , Liver Function Tests , Liver Transplantation , Male , Middle Aged , Oligopeptides/adverse effects , Pilot Projects , Pyridines/adverse effects , Treatment Outcome , Viral LoadABSTRACT
Lipodystrophy (LD) includes morphologic changes that are distressing to patients with HIV. We tested the validity of an Italian version of the Assessment of Body Change and Distress (ABCD) questionnaire and analysed its relationship to physical and mental aspects of Health-Related Quality of Life. Two hundred and fifty-two patients completed the questionnaires. Construct validity of the ABCD was tested against the MOS-HIV Health Survey, body mass-index (BMI) and CD4+ T-lymphocyte counts. Cronbach's alpha for the ABCD total score was 0.94. The ABCD showed the hypothesized moderate correlations to MOS-HIV scales and clinical variables. Preliminary evidence supports the reliability and validity of the Italian version of the ABCD in people with HIV and LD. This questionnaire may be useful to identify people experiencing greater impact of LD, or to evaluate the impact of interventions to treat LD such as plastic surgery.
