Ron M. Kagan

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Determining the phenotypic impacts of reverse transcriptase (RT) mutations on individual nucleoside RT inhibitors (NRTIs) has remained a statistical challenge because clinical NRTI-resistant HIV-1 isolates usually contain multiple mutations, often in complex patterns, complicating the task of determining the relative contribution of each mutation to HIV(More)
BACKGROUND Rapid progression to AIDS after acute infection with a multidrug-resistant (MDR), dual-tropic strain of human immunodeficiency virus type 1 (HIV-1) was reported in a New York City man (hereafter referred to as "NYC") who has sex with men. The probable source of this HIV-1 (hereafter referred to as "CT01") and the development of a recombinant MDR(More)
We established a database of HIV-1 reverse transcriptase (RT) and protease (PR) sequences and mutations to monitor the prevalence of antiretroviral drug resistance and mutational patterns in clinical samples submitted for testing to a major U.S. reference laboratory. At the end of 1998, 80% of the clinical samples tested harbored HIV strains with(More)
Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs) is associated with the emergence of resistance-associated mutations. Treatment-characterized datasets have been used to identify novel treatment-associated protease mutations. In this study, we utilized two large reference laboratory databases (>115,000 viral sequences) to(More)
OBJECTIVES The introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance. METHODS We analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations(More)
Drug resistance resulting from reverse transcriptase (RT) mutations is one of the main obstacles to successful hepatitis B virus (HBV) therapy. Indeed, HBV treatment guidelines recommend HBV genotypic resistance testing for patients receiving nucleos(t)ide RT inhibitors (N(t)RTIs) who develop virological failure. N(t)RTI-resistance mutations at 10 RT(More)
While the selection of amino acid insertions in human immunodeficiency virus (HIV) reverse transcriptase (RT) is a known mechanism of resistance against RT inhibitors, very few reports on the selection of insertions in the protease (PR) coding region have been published. It is still unclear whether these insertions impact protease inhibitor (PI) resistance(More)
BACKGROUND Virological failure of first-line antiretroviral therapy based on lopinavir boosted with ritonavir (lopinavir/r) has rarely been associated with resistance in protease. We identified a new genotypic resistance pathway in 3 patients who experienced failure of first-line lopinavir/r treatment. METHODS Viral protease and the C-term part of Gag(More)
Mutations in HIV-1 drug targets lead to resistance and consequent therapeutic failure of antiretroviral drugs. Phenotypic resistance assays are time-consuming and costly, and genotypic rules-based interpretations may fail to predict the effects of multiple mutations. We have developed a computational procedure that rapidly evaluates changes in the binding(More)
The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. Site-directed K70E mutants had a replication(More)