Clinically relevant interpretation of genotype for resistance to abacavir

Brun‐Vézinet, Françoise; Descamps, Diane; Ruffault, Annick; Masquelier, Bernard; Cálvez, Vincent; Peytavin, Gilles; Telles, Fabienne; Morand‐Joubert, Laurence; Meynard, Jean-Luc; Vray, Muriel; Costagliola, Dominique

doi:10.1097/00002030-200308150-00008

Cited by 58 publications

(64 citation statements)

References 15 publications

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“…It is now widely recognized that correlation studies analyzing the virologic response in treatment-experienced patients according to the genotypic profile at baseline provide relevant information for establishing resistance algorithms (1,12). A stepwise methodology for the development and validation of clinically relevant genotypic resistance scores for antiretroviral drugs has been proposed, and it has been shown for abacavir that this methodology provided the best prediction of the virologic response to abacavir compared to other available algorithms (1; C. Cabrera, A. Cozzi-Lepri, A. N. Phillips, C. Loveday, T. Puig, O. Kirk, M. Ait-Khaled, B. Ledergerber; J. Lundgren, B. Clotet, and L. Ruiz, Abstr.…”

Section: Discussionmentioning

confidence: 99%

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Clinically Relevant Genotype Interpretation of Resistance to Didanosine

Marcelin

Flandre

Pavie

et al. 2005

Antimicrob Agents Chemother

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We analyzed the didanosine (ddI) arm of the randomized, placebo-controlled Jaguar trial in order to define a genotypic score for ddI associated with virologic response. In this arm, 111 patients experiencing virologic failure received ddI in addition to their current combination therapy for 4 weeks. The impact of mutations in the reverse transcriptase gene on the virologic response to ddI was studied in univariate analysis. Genotypic score was constructed using step-by-step analyses first including only mutations associated to poorer virologic response (scored as ؉1), while secondarily, mutations associated to a better response (scored as ؊1) were also eligible. Eight mutations were associated with a reduced response to ddI, M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F, and K219Q/E, and two mutations were associated with a better response, K70R and M184V/I. The best prediction of the virologic response to ddI was obtained with a composite score comprising mutations added and subtracted (set II, M41L ؉ T69D ؉ L74V؉ T215Y/F ؉ K219Q/E ؊ K70R ؊ M184V/I; P ‫؍‬ 4.5 ؋ 10 ؊9 ) and by comparing that to only mutations added (set I, M41L ؉ T69D ؉ L74V ؉ L210W ؉ T215Y/F ؉ K219Q/E; P ‫؍‬ 1.2 ؋ 10 ؊7 ). Patients had a human immunodeficiency virus RNA reduction of 1.24, 0.84, 0.61, 0.40, and 0.07 log 10 copies/ml when they were ranked as having a genotypic score II of ؊2, ؊1, or 0 or 1 and 2 mutations or more, respectively. In conclusion, we developed and validated a genotypic score, taking into account mutations negatively and positively impacting the virologic response to ddI.

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Section: Discussionmentioning

confidence: 99%

“…Finally, we used the bootstrap resampling method to assess the robustness of the score obtained (1,20). Multivariate analyses of the score were performed on 500 samples drawn from the 101 patients by sampling with replacement.…”

Section: Methodsmentioning

confidence: 99%

Clinically Relevant Genotype Interpretation of Resistance to Didanosine

Marcelin

Flandre

Pavie

et al. 2005

Antimicrob Agents Chemother

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“…HIV Infect., abstr PL5. 4,2004). Further studies are needed to determine the likely resistance pathway of TDF resistance among patients with multiple ZDV mutations.…”

Section: K65r: An Emerging Mutation That Confers Class Resistancementioning

confidence: 99%

Changing Patterns in the Selection of Viral Mutations among Patients Receiving Nucleoside and Nucleotide Drug Combinations Directed against Human Immunodeficiency Virus Type 1 Reverse Transcriptase

Wainberg

Brenner

Turner

2005

Antimicrob Agents Chemother

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“…Patients with four TAMs in combination with M184V and L74V have minimal virologic responses to ABC-based regimens. 68,69 Other mutations conferring high-level resistance to both ABC and 3TC in combination with TAMs are the T69 insertion mutation and the presence of E44D plus V1181. The Q151M complex also results in resistance to both drugs.…”

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confidence: 99%