Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment.

Background: Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors.

Unboosted fosamprenavir is associated with low drug exposure in HIV-infected patients with mild-moderate liver impairment resulting from HCV-related cirrhosis.

Objectives: The aim of this study was to compare amprenavir pharmacokinetics in HIV/hepatitis C virus (HCV)-co-infected cirrhotic patients receiving non-boosted fosamprenavir 700 mg twice daily with HCV/HIV-co-infected non-cirrhotic subjects and HIV-mono-infected subjects receiving fosamprenavir/ritonavir 700/100 mg twice daily. Liver stiffness at baseline and alanine aminotransferase levels at baseline and during follow-up were measured in order to find a correlation between drug levels and liver fibrosis or hepatotoxicity.

Methods: Amprenavir plasma concentration was determined by HPLC.

Pharmacokinetic and pharmacodynamic determinants of early virological response to enfuvirtide-based regimens in HIV-positive patients.

Background: Early virological response (VR) to enfuvirtide-based salvage regimens at week 12 has been described as a predictor of long-term therapeutic success. The relationship between enfuvirtide plasma exposure and VR has not yet been investigated in the clinical setting. Our aim was to investigate the role of enfuvirtide plasma exposure as a determinant of early VR in the clinical setting.

Does iatrogenic scleroderma due to injection-site reaction to enfuvirtide impair absorption of the drug?

Background: Chronic iatrogenic scleroderma is a possible obstacle to the absorption of subcutaneously administered drugs. This study correlated the clinical and histopathological pattern of injection-site reactions (ISRs) to the pharmacokinetics of enfuvirtide in patients with HIV.

Methods: Fourteen patients treated with an enfuvirtide-based antiretroviral regimen for a median of 45 weeks were enrolled and their ISRs were evaluated.

Tipranavir (TPV) genotypic inhibitory quotient predicts virological response at 48 weeks to TPV-based salvage regimens.

The virological response (VR) to a tipranavir-ritonavir (TPV-RTV)-based regimen had been shown to be associated with a number of mutations in the protease gene, the use of enfuvirtide (T20), and the TPV phenotypic inhibitory quotient (IQ). The role of the TPV genotypic IQ (gIQ) has not yet been fully investigated. The aim of our study was to evaluate the relationship between the TPV gIQ and the VR at 48 weeks to TPV-based salvage regimens.

A simple and sensitive assay for determining plasma tipranavir concentration in the clinical setting by new HPLC method.

A simple method for the quantification of tipranavir, the first non-peptidic HIV protease inhibitor, was developed and validated. Quinoxaline, as internal standard, was added to 50 microl of plasma before a liquid-liquid extraction by 600 microl of protein precipitation solution. The extracts were diluted before being injected in the chromatographic system.

Validation of liquid/liquid extraction method coupled with HPLC-UV for measurement of ribavirin plasma levels in HCV-positive patients.

Measurement of ribavirin plasma levels in HCV-positive patients have been shown to be useful in order to optimise individual ribavirin exposure. Efficacy and toxicity of this drug are shown to be concentration-dependant. A simple HPLC-UV method was developed and validated, which has an easy liquid/liquid extraction, sensitive limit of detection, without any interference peaks, reproducible and linear over the range of clinical relevant concentrations.

An improved HPLC fluorimetric method for the determination of enfuvirtide plasma levels in HIV-infected patients.

An improved HPLC fluorimetric method for the quantification of enfuvirtide in plasma of HIV-infected subjects was described and validated. The use of an internal standard improved the reproducibility and precision of the analysis. Our method showed lower limits of detection and quantification (LOD = 32 ng/mL, LOQ = 78 ng/mL), lower intraday (RSD% 1.

Changes in nevirapine plasma concentrations over time and its relationship with liver enzyme elevations.

Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP C(trough) over time, as well as the impact of NVP C(trough) concentrations and the role of chronic hepatitis C on the incidence of liver enzyme elevations over a 48-week study period in HIV-infected patients on NVP therapy.

Short communication: liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection.

Liver toxicity is a common side effect of antiretroviral therapy, particularly in subjects coinfected with the hepatitis C virus (HCV). The incidence of severe liver toxicity after initiation of treatment with lopinavir (LPV) as well as its possible association with LPV plasma levels were assessed in 120 HIV-infected patients (52% coinfected by HCV). The incidence of severe liver toxicity at 3 months was 1.

Short communication: interactions between nevirapine plasma levels, chronic hepatitis C, and the development of liver toxicity in HIV-infected patients.

Both chronic hepatitis C and nevirapine (NVP) use are risk factors for transaminase elevation under highly active antiretroviral therapy. NVP is metabolized in the liver and its clearance could be altered in the presence of chronic hepatitis C virus (HCV) infection, enhancing the risk of liver toxicity. We examined NVP plasma levels in 70 HIV-infected subjects receiving NVP-containing triple combinations.

Does an increase in nevirapine plasma levels cause complete virologic suppression in patients experiencing early virologic failure?

Background: Patients on two nucleoside analogs plus nevirapine (NVP) who show low-level plasma HIV RNA might have insufficient NVP plasma levels and therefore might benefit from an increase in NVP dosing.

Method: The dose of NVP was increased from 400 mg/day to 600 mg/day in 25 participants taking NVP-containing triple combinations for at least 3 months and experiencing a first virological failure (>50 HIV RNA copies/mL). The levels of NVP were measured in plasma samples taken prior to and 3 months after the intervention.