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BACKGROUND Among persons in North America who are newly infected with the human immunodeficiency virus (HIV), the prevalence of transmitted resistance to antiretroviral drugs has been estimated at 1 to 11 percent. METHODS We performed a retrospective analysis of susceptibility to antiretroviral drugs before treatment and drug-resistance mutations in HIV(More)
Although combination antiretroviral therapy has resulted in a considerable improvement in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, the emergence of resistant virus is a significant obstacle to the effective management of HIV infection and AIDS. We have developed a novel phenotypic drug susceptibility assay that may be(More)
Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for(More)
Recently, significant numbers of individuals with primary human immunodeficiency virus (HIV) infection have been found to harbor viral strains with reduced susceptibility to antiretroviral drugs. In one study, HIV from 16% of such antiretroviral-naive individuals was shown to have a susceptibility to nonnucleoside reverse transcriptase (RT) inhibitors(More)
Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or "biological cutoffs," for the PhenoSense HIV phenotypic drug susceptibility assay. Definition of the natural variation in drug susceptibility in wild-type human immunodeficiency virus (HIV) type(More)
HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from(More)
The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subtype B infected individuals undergoing(More)
PURPOSE OF REVIEW HIV entry into cells is mediated through sequential interactions between HIV envelope proteins (Env) and two cellular molecules: CD4 and a co-receptor, typically either CCR5 or CXCR4. Co-receptor preference has been associated with other viral traits; specifically, CXCR4-tropic viruses have been associated with increased host cell(More)
Although fitness landscapes are central to evolutionary theory, so far no biologically realistic examples for large-scale fitness landscapes have been described. Most currently available biological examples are restricted to very few loci or alleles and therefore do not capture the high dimensionality characteristic of real fitness landscapes. Here we(More)
Although present as polymorphisms in HIV-1 sequences from untreated patients, mutations at reverse transcriptase (RT) codon 207 are found at higher frequency in samples from zidovudine-treated patients. Introduction of the Q207D mutation into the RT of a zidovudine (ZDV)-resistant isolate by site-directed mutagenesis increased ZDV resistance 2.7-fold but(More)