Our results support the hypothesis of the association of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. R77Q does not seem to be linked to a particular viral strain but might be associated to immunologic selection. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr.
In our study we examined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activity of a novel HIV-1 protease inhibitor, PNU-140690 (tipranavir), against patient-derived isolates resistant to multiple other protease inhibitors (PIs). The aim of our experiments was to investigate the genotypes and the in vitro phenotypes of drug resistance of PNU-140690. We carried out drug susceptibility tests with peripheral blood mononuclear cells and a fixed amount of infectious virus (1,000 50% tissue culture infective doses) to determine the 50% inhibitory concentration (IC 50 ) and IC 90 , PCR assays for the detection of drug resistance mutations in RNA in plasma, and direct sequencing of PCR products. Phenotypic resistance to PIs was invariably related to genotypic mutations. The substitutions among the amino acid residues of the protease included L10I, K20R, L24I, M36I, N37D, G48V, I54V, L63P, I64V, A71V, V77I, V82A, I84V, and L90M. Isolates from all of the patients had developed a maximal degree of resistance to indinavir, ritonavir, and nelfinavir (IC 50 s, >0.1 M). We also compared these mutations with the amino acid changes previously described in association with in vivo tipranavir administration. The mutations included the following: I15V, E35D, N37D, R41K, D60E, and A71T.
The mean total cost per year to provide health care to HIV-positive patients was stable during the period 2004-2007, with an increase of HAART percentage impact on the total cost. Several clinical characteristics of HIV-infected patients were significantly associated with cost variation.
We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stromaderived factor 1 (SDF-1), Met-SDF-1, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1 had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.In 1995, Cocchi et al. reported potent in vitro human immunodeficiency virus type 1 (HIV-1) inhibition by three chemokines secreted by CD8 ϩ T lymphocytes (4) and focused attention on this class of molecules with low molecular masses (8 to 12 kDa). The chemokines described, RANTES, macrophage inflammatory protein-1␣ (MIP-1␣), and MIP-1, belong to the group of C-C chemokines that block HIV-1 entry into cells (5).Relationships among membrane coreceptors, chemokines, and cellular tropism were further defined in 1996 by Feng et al., who described a novel molecule which acted as a cofactor for T-cell-tropic HIV-1 isolates but not for macrophage-tropic isolates (14). This receptor, which was already known but did not have an identified natural ligand, belongs to the C-X-C chemokine receptor superfamily and was named "fusin," or CXCR4. The receptor for HIV-1 macrophage-tropic isolates was subsequently identified and named C-C chemokine receptor 5 (CCR5). CCR5 reacts with the chemokines RANTES, MIP-1␣, and MIP-1 (9, 12). The natural ligand for CXCR4 is stroma derived factor-1 (SDF-1), an ␣-chemokine with chemotactic properties for T lymphocytes and a developmental role in B lymphocyte maturation (2,25).During the early phases of HIV-1 infection, R5 viral strains usually predominate, whereas X4 strains frequently emerge in the late stages of HIV-1 infection, accompanied by a decline in peripheral blood CD4 lymphocytes and a clinical progression toward AIDS (7,34). Viral isolates with a dual tropism could represent a transition phase between viral R5 and X4 phenotypes, or they may represent X4 viruses that have maintained an ability to infect macrophages (31, 33).The aim of our study was to evaluate the interactions between attachment and entry inhibitors of HIV-1 infection. Our experiments suggest that the use of combined inhibitors of R5 and X4 viruses may be useful in inhibiting mixed infections. Analysis of cellular tropism of the different viral isolates on transformed cell lines. The two viral isolates examined in this study, RM and DK, were derived from two patients with primary HIV-1 infection acute syndrome (29), and the isolates were used to infect U87MG-transformed CD4 ϩ cells transfected with CCR5 or CXCR4 coreceptors (8), provided by Dan R. Littman (The Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New Yo...
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