Linked Life Data

21576473

Source:http://linkedlifedata.com/resource/pubmed/id/21576473

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2011-6-1
pubmed:abstractText
In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) ? 6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/1 U01-AI068634, http://linkedlifedata.com/resource/pubmed/grant/1 U01AI068636-01, http://linkedlifedata.com/resource/pubmed/grant/1U01 AI069494-01, http://linkedlifedata.com/resource/pubmed/grant/3U01AI32775-13S5, http://linkedlifedata.com/resource/pubmed/grant/5 U01AI069518, http://linkedlifedata.com/resource/pubmed/grant/5U01AI069455-03, http://linkedlifedata.com/resource/pubmed/grant/5U01AI069456-03, http://linkedlifedata.com/resource/pubmed/grant/AI-069501, http://linkedlifedata.com/resource/pubmed/grant/AI69426, http://linkedlifedata.com/resource/pubmed/grant/AI69453, http://linkedlifedata.com/resource/pubmed/grant/IAAY1AI8374, http://linkedlifedata.com/resource/pubmed/grant/U01AI068636, http://linkedlifedata.com/resource/pubmed/grant/U01AI069436, http://linkedlifedata.com/resource/pubmed/grant/U01AI69463-03
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9202-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine.
pubmed:affiliation
National Cancer Institute, Frederick, MD 21702, USA.
pubmed:publicationType
Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural