Mark Holodniy

Publication Details

  • Connection Domain Mutations in Treatment-Experienced Patients in the OPTIMA Trial JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Dau, B., Ayers, D., Singer, J., Harrigan, P. R., Brown, S., Kyriakides, T., Cameron, D. W., Angus, B., Holodniy, M. 2010; 54 (2): 160-166

    Abstract:

    To determine the frequency of mutations in the connection domain (CD) of HIV reverse transcriptase in treatment-experienced patients in the Options in Management with Antiretrovirals trial, their impact on susceptibility to antiretroviral (ARV) drugs, and their impact on virologic outcomes.Baseline plasma ARV genotypes and inferred resistance phenotypes were obtained. Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G were compared with a treatment-naive population. The association of CD mutations with inferred IC50 fold changes to nucleos(t)ide reverse transcriptase inhibitors was evaluated. Univariate and multivariate analyses examined the association of CD mutations with a >1 log10 per milliliter decrease in HIV viral load after 24 weeks on a new ARV regimen.Higher CD mutation rates were seen in Options in Management with Antiretrovirals patients (n = 345) compared with a treatment-naive population. CD mutations were associated with increased inferred IC50 fold changes to abacavir, stavudine, tenofovir, and zidovudine. On univariate analysis, A371V was associated with lack of virologic response, as was having any CD mutation on multivariate analysis.CD mutations are frequent in treatment-experienced populations. They are associated with reduced susceptibility to some nucleos(t)ide reverse transcriptase inhibitors and with a diminished response to ARV therapy.

    View details for DOI 10.1097/QAI.0b013e3181cbd235

    View details for Web of Science ID 000278100600008

    View details for PubMedID 20130473

Stanford Medicine Resources:

Footer Links: