The Experts below are selected from a list of 59988 Experts worldwide ranked by ideXlab platform
Fabrizio Mammano - One of the best experts on this subject based on the ideXlab platform.
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Impact of the HIV integrase genetic context on the phenotypic expression and in vivo dynamics of integrase inhibitor Resistance mutations
Retrovirology, 2013Co-Authors: Nga Nguyen, François Clavel, Sylvie Rato, Constance Delaugerre, Fabrizio MammanoAbstract:Background HIV Resistance to the integrase inhibitor raltegravir (RAL) in treated patients is characterized by three main distinct Resistance pathways, for which the primary mutations are: N155H, Q148H/K/R, or Y143R/H/C. These genotypes may emerge sequentially, always carried by distinct viral genomes. The mechanism explaining the sequential emergence and in vivo dynamics along with viral escape from RAL treatment are poorly understood. We hypothesize that differences in the in vivo dynamics of HIV Resistance to RAL, which must be a direct consequence of the phenotypic expression of viral Resistance and/or of viral fitness, are due to the genetic context of the integrase carried by viral variants infecting individual patient.
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Role of Gag in HIV Resistance to Protease Inhibitors.
Viruses, 2010Co-Authors: François Clavel, Fabrizio MammanoAbstract:Cleavage of Gag and Gag-Pol precursors by the viral protease is an essential step in the replication cycle of HIV. Protease inhibitors, which compete with natural cleavage sites, strongly impair viral infectivity and have proven to be highly valuable in the treatment of HIV-infected subjects. However, as with all other antiretroviral drugs, the clinical benefit of protease inhibitors can be compromised by Resistance. One key feature of HIV Resistance to protease inhibitors is that the mutations that promote Resistance are not only located in the protease itself, but also in some of its natural substrates. The best documented Resistance-associated substrate mutations are located in, or near, the cleavage sites in the NC/SP2/p6 region of Gag. These mutations improve interactions between the substrate and the mutated enzyme and correspondingly increase cleavage. Initially described as compensatory mutations able to partially correct the loss of viral fitness that results from protease mutations, changes in Gag are now recognized as being directly involved in Resistance. Besides NC/SP2/p6 mutations, polymorphisms in other regions of Gag have been found to exert various effects on viral fitness and or Resistance, but their importance deserves further evaluation.
Daniel J. Skiest - One of the best experts on this subject based on the ideXlab platform.
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Low prevalence of primary HIV Resistance in western Massachusetts.
Journal of the International Association of Physicians in AIDS Care (Chicago Ill. : 2002), 2010Co-Authors: Dmitri Iarikov, Melina Irizarry-acosta, Claudia Martorell, Robert P. Hoffman, Daniel J. SkiestAbstract:Most studies of primary antiretroviral (ARV) Resistance have been conducted in large metropolitan areas with reported rates of 8% to 25%. We collected data on 99 HIV-1-infected antiretroviral-naive patients from several sites in Springfield, MA, who underwent genotypic Resistance assay between 2004 and 2008. Only major Resistance mutations per International AIDS Society-USA (IAS-USA) drug Resistance mutations list were considered. The prevalence of Resistance was 5% (5 of 99). Three patients had one nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation: 103N, 103N, and 190A, 1 patient had a protease inhibitor (PI) mutation: 90M; and 1 patient had 3-class Resistance with NNRTI: 181C, 190A, PI: 90M, and nucleoside analogue reverse transcriptase inhibitor (NRTI): 41L, 210W. Mean time from HIV diagnosis to Resistance testing was shorter in patients with Resistance versus those without: 9 (range 0.3-42 months) versus 27 (range 0.1-418 months), P = .11. There was a trend to lower mean CD4 count in thos...
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Use of HIV Resistance testing after prolonged treatment interruption.
Journal of acquired immune deficiency syndromes (1999), 2010Co-Authors: Dmitri Iarikov, Melina Irizarry-acosta, Claudia Martorell, Carol A. Rauch, Robert P. Hoffman, Daniel J. SkiestAbstract:Background: HIV-1 genotypic Resistance testing is not routinely recommended for patients who have been off antiretroviral therapy (ART) for longer than 4 weeks. We assessed the results and use of Resistance testing in patients off ART. Methods: All HIV Resistance genotypes from November 2003 through April 2008 were reviewed from one large teaching hospital and two private HIV practices. Inclusion criterion was having a genotypic Resistance test after an ART interruption of at least 2 months. Medical records were reviewed using a standardized data collection sheet. Results: Sixty-two of 304 treatment-experienced patients with HIV genotypes met the inclusion criteria. Prior cumulative ART class exposure included nucleoside reverse transcriptase inhibitors in 54 patients, nonnucleoside reverse transcriptase inhibitors in 32 patients, and protease inhibitors in 30 patients. Resistance testing was performed at a mean of 12 months (range, 2.5-48 months) after ART interruption. The mean time between ART interruption and Resistance testing did not differ for patients with mutations and those without mutations detected. Seventeen of 62 (27.4%) patients were found to have Resistance mutations. Eleven patients were found to have mutations to nonnucleoside reverse transcriptase inhibitors, four patients had mutations to nucleoside reverse transcriptase inhibitors, and two patients had protease inhibitor-associated mutations. No patient had multiclass Resistance. Among the 17 patients with mutations after treatment interruption, 15 had mutations that were either not present on a prior genotype (n = 2) or did not have a prior genotype (n = 13). Conclusions: HIV genotypic Resistance assays may identify mutations even when performed after a prolonged treatment interruption and may offer clinically significant information. Current guidelines that discourage Resistance testing after treatment interruptions of longer than 4 weeks should be re-evaluated.
François Clavel - One of the best experts on this subject based on the ideXlab platform.
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Impact of the HIV integrase genetic context on the phenotypic expression and in vivo dynamics of integrase inhibitor Resistance mutations
Retrovirology, 2013Co-Authors: Nga Nguyen, François Clavel, Sylvie Rato, Constance Delaugerre, Fabrizio MammanoAbstract:Background HIV Resistance to the integrase inhibitor raltegravir (RAL) in treated patients is characterized by three main distinct Resistance pathways, for which the primary mutations are: N155H, Q148H/K/R, or Y143R/H/C. These genotypes may emerge sequentially, always carried by distinct viral genomes. The mechanism explaining the sequential emergence and in vivo dynamics along with viral escape from RAL treatment are poorly understood. We hypothesize that differences in the in vivo dynamics of HIV Resistance to RAL, which must be a direct consequence of the phenotypic expression of viral Resistance and/or of viral fitness, are due to the genetic context of the integrase carried by viral variants infecting individual patient.
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Role of Gag in HIV Resistance to Protease Inhibitors.
Viruses, 2010Co-Authors: François Clavel, Fabrizio MammanoAbstract:Cleavage of Gag and Gag-Pol precursors by the viral protease is an essential step in the replication cycle of HIV. Protease inhibitors, which compete with natural cleavage sites, strongly impair viral infectivity and have proven to be highly valuable in the treatment of HIV-infected subjects. However, as with all other antiretroviral drugs, the clinical benefit of protease inhibitors can be compromised by Resistance. One key feature of HIV Resistance to protease inhibitors is that the mutations that promote Resistance are not only located in the protease itself, but also in some of its natural substrates. The best documented Resistance-associated substrate mutations are located in, or near, the cleavage sites in the NC/SP2/p6 region of Gag. These mutations improve interactions between the substrate and the mutated enzyme and correspondingly increase cleavage. Initially described as compensatory mutations able to partially correct the loss of viral fitness that results from protease mutations, changes in Gag are now recognized as being directly involved in Resistance. Besides NC/SP2/p6 mutations, polymorphisms in other regions of Gag have been found to exert various effects on viral fitness and or Resistance, but their importance deserves further evaluation.
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HIV Resistance to raltegravir
European Journal of Medical Research, 2009Co-Authors: François ClavelAbstract:Similar to all antiretroviral drugs, failure of raltegravirbased treatment regimens to fully supress HIV replication almost invariably results in emergence of HIV Resistance to this new drug. HIV Resistance to raltegravir is the consequence of mutations located close to the integrase active site, which can be divided into three main evolutionary pathways: the N155H, the Q148R/H/K and the Y143R/C pathways. Each of these primary mutations can be accompanied by a variety of secondary mutations that both increase Resistance and compensate for the variable loss of viral replicative capacity that is often associated with primary Resistance mutations. One unique property of HIV Resistance to raltegravir is that each of these different Resistance pathways are mutually exclusive and appear to evolve separately on distinct viral genomes. Resistance is frequently initiated by viruses carrying mutations of the N155H pathway, followed by emergence and further dominance of viral genomes carrying mutations of the Q148R/H/K or of the Y143R/C pathways, which express higher levels of Resistance. Even if some natural integrase polymorphisms can be part of this evolution process, these polymorphisms do not affect HIV susceptibility in the absence of primary mutations. Therefore, all HIV-1 subtypes and groups, together with HIV-2, are naturally susceptible to raltegravir. Finally, because interaction of integrase strand transfer inhibitors with the HIV integrase active site is comparable from one compound to another, raltegravir-resistant viruses express significant cross Resistance to most other compounds of this new class of antiretroviral drugs.
Patricia Recordon-pinson - One of the best experts on this subject based on the ideXlab platform.
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Predominance of CRF06_cpx and Transmitted HIV Resistance in Algeria: Update 2013–2014
AIDS research and human retroviruses, 2015Co-Authors: Akila Abdellaziz, Jennifer Papuchon, Safia Khaled, Dalila Ouerdane, Hervé Fleury, Patricia Recordon-pinsonAbstract:Since 2008, no data on HIV diversity or the transmission rate of HIV Resistance mutations in naive patients have been presented for Algeria, a country of MENA region. Between 2013 and 2014, we studied 152 samples including 89 naive patients. The current study describes the change in HIV diversity in Algeria with the predominance of CRF06_cpx and the huge increase of transmitted HIV Resistance, which now reaches 15%.
Hawazin Faruki - One of the best experts on this subject based on the ideXlab platform.
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Update on HIV Resistance and Resistance testing.
Medicinal research reviews, 2003Co-Authors: Joseph Sebastian, Hawazin FarukiAbstract:The introduction of highly active antiretroviral therapy, including a combination of antivirals directed at various steps in the viral life cycle, has led to significant decreases in morbidity and mortality associated with human immunodeficiency virus (HIV-1) infections. Despite the availability of numerous antivirals, many extensively treated patients gradually loose the ability to control viral replication because of development of antiviral Resistance. Laboratory tests have been developed and validated to assist in recognizing such Resistance and to help predict which antivirals may be more likely to control viral replication in a given patient. Both genotypic and phenotypic assays have been developed to assess HIV-1 antiviral Resistance. The assay methodologies, including the advantages and disadvantages of each method, as well as the limitations of each method are reviewed. The ability to predict likely drug response from a genotype or a phenotype is continually evolving, and the more recently discovered mutation/drug Resistance associations are discussed in terms of their implications for HIV Resistance assays. To provide additional options for those who have developed Resistance to all currently available drugs, new antivirals, such as the fusion inhibitors, are being developed. These new classes of antivirals block the HIV viral life cycle at sites other than reverse transcriptase and protease. Unique and novel Resistance assays are being developed to measure HIV Resistance to these new drugs.
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HIV Resistance Testing: Methods, Utility, and Limitations
Molecular Diagnosis, 2000Co-Authors: Timothy M. Alcorn, Hawazin FarukiAbstract:Widespread use of combination antiretroviral therapy for HIV has led to increased incidence of HIV Resistance and a need for antiretroviral Resistance testing to optimize therapeutic choices. Antiretroviral Resistance analysis is performed using either genotypic or phenotypic assays. Genotypic assays identify Resistance-associated mutations in the HIV genome. They are faster and less technically demanding than phenotypic assays; however, the associations between mutations and Resistance patterns are often complicated, making interpretation difficult. Phenotypic assays directly measure the ability of antiviral compounds to inhibit replication of patient-derived virus. Phenotypic assays provide results that are easier to interpret; however, there is little data that relates the degree of Resistance detected in phenotypic assays to patient clinical response. Despite limitations, the improved therapeutic outcome of therapies guided by Resistance testing is leading to incorporation of Resistance testing into the standard of care for HIV treatment.