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Using quantitative deep HIV-1 sequencing in a subject who developed virological failure to deep salvage therapy with raltegravir, we found that most Q148R and N155H mutants detected at the time of virological failure originated from pre-existing minority Q148R and N155H variants through independent evolutionary clusters. Double 148R+N155H mutants were also(More)
Computational analysis of the variations in the HIV-1 genome sequence that correlate with preferential binding to the CCR5 (C-Cmotif receptor 5) or CXCR4 (C-X-C motif receptor 4) coreceptors in the host promises to enhance the prediction of disease pathogenesis and enable the optimization of treatment regimes. With new HIV drugs targeting coreceptors(More)
Human immunodeficiency virus-1 tropism highly correlates with the amino acid (aa) composition of the third hypervariable region (V3) of gp120. A shift towards more positively charged aa is seen when binding to CXCR4 compared with CCR5 (X4 vs. R5 strains), especially positions 11 and 25 (11/25-rule) predicting X4 viruses in the presence of positively charged(More)
Maraviroc (MVC) is the first licensed antiretroviral drug from the class of coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by the majority of HIV strains in order to infect the human immune cells (Fig. 1). Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used, is determined in the virus by the Env(More)
BACKGROUND The Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies compared maraviroc versus placebo in treatment-experienced patients with CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1), screened using the original Trofile assay. A subset with non-R5 HIV infection entered the A4001029(More)
Reaction center concentrations were determined in chloroplasts of tobacco, cv John William's Broadleaf, and its mutants Su/su and Su/su var. Aurea. Quantum yields of the primary reactions of Photosystems I, II alpha and II beta (Melis, A. and Homann, P.H. (1975) Photochem. Photobiol. 21, 431--437) were obtained by measurement of their rate constants and the(More)
BACKGROUND Genotypic drug resistance testing provides essential information for guiding treatment in HIV-infected patients. It may either be used for identifying patients with transmitted drug resistance or to clarify reasons for treatment failure and to check for remaining treatment options. While different approaches for the interpretation of HIV sequence(More)
BACKGROUND The MOTIVATE-1 and 2 studies compared maraviroc (MVC) along with optimized background therapy (OBT) vs. placebo along with OBT in treatment-experienced patients screened as having R5-HIV (original Monogram Trofile). A subset screened with non-R5 HIV were treated with MVC or placebo along with OBT in a sister safety trial, A4001029. This analysis(More)
BACKGROUND Inferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4) variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing.(More)
OBJECTIVE To explore the potential of deep HIV-1 sequencing for adding clinically relevant information relative to viral population sequencing in heavily pre-treated HIV-1-infected subjects. METHODS In a proof-of-concept study, deep sequencing was compared to population sequencing in HIV-1-infected individuals with previous triple-class virological(More)