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OBJECTIVES The objective of this study was to evaluate the incidence, prevalence and clinical consequences of virological failure (VF) to raltegravir-based regimens in Spain. METHODS A multicentre, retrospective, observational study was performed in 10 tertiary hospitals (January 2006 to June 2013). The study included HIV-1-infected patients with loss of(More)
Antifolate inhibitors of thymidylate synthase (TS) have primarily been based on the structure of folic acid. This paper describes the identification and development of novel 6,7-imidazotetrahydroquinoline TS inhibitors by iterative ligand design, synthesis, and crystallographic analysis of protein-inhibitor complexes. Beginning with a high-resolution(More)
Dendritic cells (DCs) are essential antigen-presenting cells for the induction of immunity against pathogens. However, HIV-1 spread is strongly enhanced in clusters of DCs and CD4(+) T cells. Uninfected DCs capture HIV-1 and mediate viral transfer to bystander CD4(+) T cells through a process termed trans-infection. Initial studies identified the C-type(More)
A class of potent nonpeptidic inhibitors of human immunodeficiency virus protease has been designed by using the three-dimensional structure of the enzyme as a guide. By employing iterative protein cocrystal structure analysis, design, and synthesis the binding affinity of the lead compound was incrementally improved by over four orders of magnitude. An(More)
OBJECTIVES The aim of this study was to characterize the prevalence and patterns of genotypic integrase inhibitor (INI) resistance in relation to HIV-1 clade. METHODS The cohort comprised 533 INI-naive subjects and 255 raltegravir recipients with viraemia who underwent integrase sequencing in routine care across Europe, including 134/533 (25.1%) and(More)
The design, synthesis, and crystallographic analysis of protein-inhibitor complexes is described for a novel series of nonpeptidic HIV protease (HIV Pr)inhibitors. Beginning with a cocrystal structure of a Phe-Pro peptidomimetic bound to the HIV Pr, design was initiated that resulted in the substituted 2-butanol compound 8 as the lead compound (Ki = 24.5(More)
OBJECTIVE To compare speech development following unilateral cochlear implant (CI) between a group of prelingually deaf children who have been educated exclusively using spoken language and another group who have used two languages (spoken and sign language). DESIGN A simple group quasi-experimental design was used with a control group. METHODS The(More)
OBJECTIVE The study of HIV-1 rapid progressors has been limited to specific case reports. Nevertheless, identification and characterization of the viral and host factors involved in rapid progression are crucial when attempting to uncover the correlates of rapid disease outcome. DESIGN We carried out comparative functional analyses in rapid progressors (n(More)
The aim of this study is to obtain knowledge about habits related to addictive behaviour (pathological gambling, Internet, compulsive shopping, use of mobile telephones, etc.) that may be displayed by young students at the University of Cordoba (Spain), and to relate this behaviour with variables such as age, sex, course year, macro-field of study(More)
Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV)(More)