D. Gonzalez de Requena

TL;DR: This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure.

Abstract: ABSTRACT 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. Patients placed on regimens containing two nucleoside reverse transcriptase inhibitors plus TPV-RTV 500/200 mg twice a day with or without T20 were prospectively studied. Regular follow-up was performed over the study period. VR, considered a viral load (VL) decrease of ≥1 log unit and/or the achievement of <50 copies/ml with no VL rebound of >0.5 log unit compared to the maximal VL decrease at week 48, was assessed. Thirty-eight patients who had received multiple drugs were included. At week 48 the VL decrease was −1.48 (interquartile range [IQR], −2.88 to −0.48), 15 patients (39.5%) had VLs of <50 copies/ml, and the CD4+ cell count increase was 37 cells/mm3 (IQR, −30 to +175). Twenty subjects (52.6%) achieved VRs. The TPV gIQ and optimized background score (OBS) were independently associated with higher VL decreases. The TPV gIQ and OBS were also independent predictors of a VR at week 48. TPV gIQ and OBS cutoff values of 14,500 and 2, respectively, were associated with a higher rate of VR. The TPV gIQ was shown to be able to predict the VR at 48 weeks to TPV-containing salvage regimens better than the TPV trough concentration or TPV-associated mutations alone. A possible TPV gIQ cutoff value of 14,500 for reaching a VR at week 48 was suggested. Further studies are needed in order to evaluate the calculation of TPV gIQ as a new tool for the optimization of TPV-based salvage therapy.

TL;DR: In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts.

TL;DR: Higher TPV and RTV Ctrough were found in patients administered with T20, potentially affecting Vd (higher with T 20) and elimination half-life (higher in T20 group) of TPV or RTV.