ABSTRACT
We evaluated the utility of Architect core antigen assay® Abbott Diagnostics (HCVAg) for monitoring patients with HCV infection and compared to HCV-RNA quantification (Cobas Ampliprep TaqMan-Roche Diagnostics). Samples from 262 patients were studied. Mean baseline HCV RNA and HCVAg levels were similar for responders (6.2 log IU/mL and 3.4 log fmol/L) and non-responders (6.1 log IU/mL and 3.2 log fmol/L), respectively. Only 10 patients failed to achieve SVR12 and all were detected by both assays. To evaluate HCVAg quantification as a tool for the detection of failure to DAAs, we performed a retrospective study of 132 non-responder patients. Mean HCV RNA and HCVAg levels at the time of detection of therapeutic failure were 5.88±0.97 log IU/mL and 3.19±0.79 log fmol/L, respectively. HCVAg (>3 fmol/L) was detected in 130/132 patients (98.5%). HCVAg assay was useful for patient selection and for evaluating virological response to DAAs in the real world.
Subject(s)
Antiviral Agents/therapeutic use , Drug Monitoring/methods , Hepatitis C, Chronic/drug therapy , Viral Core Proteins/blood , Female , Humans , Male , Middle Aged , RNA, Viral/blood , Retrospective StudiesABSTRACT
Etravirine (ETR) is a diarylpyrimidine derivative with a polycyclic molecule composed of 3 aromatic rings with single bonds between the rings (C(20)H(15)BrN(60)). The drug acts through a mechanism of noncompetitive inhibition on binding to a hydrophobic binding pocket, very close to the active center of the enzyme, provoking an allosteric transition to a conformation that distorts its structure and impedes DNA polymerization. The 3 rings with single bonds between the rings confer the molecule with great fl exibility and torsion. Because of these characteristics, etravirine can adapt to conformational changes in the binding pocket, including a large number of the conformations provoked by the resistance mutations that appear after failure to regimens that include efavirenz or nevirapine. This specific chemical structure largely explains the drug's distinguishing features in terms of its antiviral potency and high genetic barrier. ETR is a highly active molecule against HIV-1. This drug has a high genetic barrier to resistance and has demonstrated antiviral activity against a wide panel of recombinant viruses that incorporate resistance mutations to first-generation non-nucleoside analogues. Equally, ETR has demonstrated efficacy against several subtypes of the M group of HIV-1 (A, B, C, D, F and H, and recombinant forms CRF01_AE, CRF02_AG, CRF05_DF), as well as against isolates of HIV-1 group O. ETR, as the rest of non-nucleoside analogues, does not have demonstrated antiviral activity against HIV-2.
