Evaluation of eight different bioinformatics tools to predict viral tropism in different human immunodeficiency virus type 1 subtypes.

Human immunodeficiency virus type 1 (HIV-1) tropism can be assessed using phenotypic assays, but this is quite laborious, expensive, and time-consuming and can be made only in sophisticated laboratories. More accessible albeit reliable tools for testing of HIV-1 tropism are needed in view of the prompt introduction of CCR5 antagonists in clinical practice. Bioinformatics tools based on V3 sequences might help to predict HIV-1 tropism; however, most of these methods have been designed by taking only genetic information derived from HIV-1 subtype B into consideration.

Synergistic inhibition of protease-inhibitor-resistant HIV type 1 by saquinavir in combination with atazanavir or lopinavir.

Background: Double-boosted protease inhibitors (PIs) are under investigation for the treatment of patients who are unable to take nucleoside reverse transcriptase inhibitors because of cross-resistance and/or intolerance. Evidence of synergistic inhibition of wild-type HIV has been reported for saquinavir with atazanavir or lopinavir.

Methods: We investigated the activity of these two combinations against a panel of six site-directed mutant HIV-1 strains and 14 clinically derived recombinant HIV-1 strains presenting a range of PI-resistance profiles.

Correlation between a phenotypic assay and three bioinformatic tools for determining HIV co-receptor use.

The predictive value of three genotypic methods to determine HIV-1 co-receptor usage was assessed in 83 plasma specimens taking as reference the results obtained using a recombinant phenotypic assay (Phenoscript). The best concordance was found for webPSSM, followed by geno2pheno and wetcat (85.9, 71.

Susceptibility of HIV-1 non-B subtypes and recombinant variants to Enfuvirtide.

Background: Data on susceptibility of HIV-1 non-B subtypes to Enfuvirtide (ENF) is rather limited.

Objective: To determine if ENF could be active in vitro against HIV-1 non-B subtypes and how the gp41 genetic variability across variants may influence ENF susceptibility.

Methods: Using PHENOSCRIPT Env, a recombinant envelope virus assay, ENF susceptibility was investigated in isolates from 19 drug-naive HIV-1-infected individuals harboring non-B subtypes.

Dynamics of enfuvirtide resistance in HIV-infected patients during and after long-term enfuvirtide salvage therapy.

Enfuvirtide (ENF) is the first of a novel class of drugs that blocks HIV fusion to host cells. We analyzed the dynamics of genotypic and phenotypic resistance to ENF during and after long-term ENF therapy and its clinical implications in eight heavily treatment-experienced HIV-infected patients who underwent salvage therapy with enfuvirtide along with other antiretroviral agents. All patients showed a rapid decline in plasma HIV-RNA followed by viral rebound.

Evolution of genotypic and phenotypic resistance to Enfuvirtide in HIV-infected patients experiencing prolonged virologic failure.

Four heavily antiretroviral-experienced HIV-infected patients had significant plasma HIV-RNA reductions (>1 log) after beginning an Enfuvirtide (ENF)-based rescue regimen. However, all had viral rebound shortly thereafter, sustaining high levels of plasma viremia over 80 weeks. These patients developed rapidly genotypic and phenotypic resistance to ENF.