TY - JOUR
T1 - Sequence clusters in human immunodeficiency virus type I reverse transcriptase are associated with subsequent virological response to antiretroviral therapy
AU - Leigh Brown, Andrew J.
AU - Günthard, Huldrych F.
AU - Wong, Joseph K.
AU - D'Aquila, Richard T.
AU - Johnson, Victoria A.
AU - Kuritzkes, Daniel R.
AU - Richman, Douglas D.
N1 - Funding Information:
Financial support: National Institutes of Health grants TW00767 (Fo-garty Center), K 11 AI01361, AI 27670, AI 38858 AI 36214 (Center for AIDS Research), AI 29164, AI 32775, 96VC001, AI 40876, and AI 27767 (Center for AIDS Research); Research Center for AIDS and HIV Infection of the San Diego Veterans Affairs Medical Center and Core Laboratory Research Facilities of University of Alabama at Birmingham School of Medicine, University of Alabama at Birmingham Center for AIDS Research, and Birmingham Veterans Affairs Medical Center; and grant 84 AD-046176, Swiss National Science Foundation (H.G.).
PY - 1999
Y1 - 1999
N2 - Many amino acid (aa) sites in reverse transcriptase (RT) have been implicated in resistance to nucleoside (NRTI) and nonnucleoside antiretrovirals. Interactions between these in response to combination therapy remain poorly understood. In a trial (ACTG 241) of zidovudine/didanosine (ddI) versus zidovudine/ddI/nevirapine in nucleoside- experienced patients, baseline sequence data from the RT coding region was analyzed from 55 individuals. Sequences were clustered by use of a parsimony method and the virological responses (ratio of baseline viral load to vital load after of therapy) for each cluster were analyzed at week 8 and week 48. Both clusters and genotype at aa 215 were significantly associated with virological response at both time points, whereas vital load showed a stronger association with sequence clusters. Sequence clusters identified one group of patients who never developed high-level resistance to NRTIs despite prior nucleoside exposure and poor suppression of viral replication.
AB - Many amino acid (aa) sites in reverse transcriptase (RT) have been implicated in resistance to nucleoside (NRTI) and nonnucleoside antiretrovirals. Interactions between these in response to combination therapy remain poorly understood. In a trial (ACTG 241) of zidovudine/didanosine (ddI) versus zidovudine/ddI/nevirapine in nucleoside- experienced patients, baseline sequence data from the RT coding region was analyzed from 55 individuals. Sequences were clustered by use of a parsimony method and the virological responses (ratio of baseline viral load to vital load after of therapy) for each cluster were analyzed at week 8 and week 48. Both clusters and genotype at aa 215 were significantly associated with virological response at both time points, whereas vital load showed a stronger association with sequence clusters. Sequence clusters identified one group of patients who never developed high-level resistance to NRTIs despite prior nucleoside exposure and poor suppression of viral replication.
UR - http://www.scopus.com/inward/record.url?scp=0033375224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033375224&partnerID=8YFLogxK
U2 - 10.1086/315017
DO - 10.1086/315017
M3 - Article
C2 - 10479129
AN - SCOPUS:0033375224
SN - 0022-1899
VL - 180
SP - 1043
EP - 1049
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -
