Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data (Record no. 75400)

MARC details
000 -LEADER
fixed length control field 06332cam a2200277 4500
001 - CONTROL NUMBER
control field NMDX5902
008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION
fixed length control field 120401t2010 xxu||||| |||| 00| 0 eng d
022 ## - INTERNATIONAL STANDARD SERIAL NUMBER
International Standard Serial Number 13596535
100 ## - MAIN ENTRY--PERSONAL NAME
Personal name Price, H.
240 ## - UNIFORM TITLE
Uniform title <a href="Antiviral Therapy">Antiviral Therapy</a>
245 ## - TITLE STATEMENT
Title Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data
260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT)
Date of publication, distribution, etc. 2010
500 ## - GENERAL NOTE
General note NMUH Staff Publications
500 ## - GENERAL NOTE
General note 15
520 ## - SUMMARY, ETC.
Summary, etc. &lt;h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt;"&gt;BACHGROUND:&lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt; There is conflicting evidence onspecific reverse transcriptase inhibitors to which the&amp;nbsp;N348I&amp;nbsp;mutation&amp;nbsp;inthe&amp;nbsp;connection&amp;nbsp;domain&amp;nbsp;of HIV type-1 reverse transcriptaseconfers resistance. Here, we examined associations between the emergence of&amp;nbsp;N348I&amp;nbsp;andantiretroviral history in a large clinical database.&lt;/span&gt;&lt;/h4&gt;&lt;h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; float: left; background-position: initial initial; background-repeat: initial initial;"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;"&gt;METHODS:&lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"&gt; &lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt;We analysed 5,353 resistance tests (that were sequenced beyond codon 348)among 2,266 antiretroviral-experienced patients. Associations between&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;and individual antiretroviral&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;drug&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;exposure were estimated using amatched case-control approach. Cases were defined as the first resistance testwhere&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;was detected; for each case, the 10closest (in calendar time) N348N tests were selected as controls. Odds ratios(ORs) adjusted for effects of all other drugs were estimated by conditionallogistic regression.&lt;span style="text-transform:uppercase"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;"&gt;RESULTS:&lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"&gt; &lt;/span&gt;&lt;span class="highlight"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt;N348I&lt;/span&gt;&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt;&amp;nbsp;&lt;/span&gt;&lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt;was detected in 198 (8.7%)cases. Drugs that were statistically significantly positively associated with&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;were efavirenz (OR 1.55, 95%confidence interval [CI] 1.08-2.23; P=0.017) and nevirapine (OR 2.06, 95% CI1.49-2.85; P&amp;lt;0.001). Tenofovir disoproxil fumarate (TDF) was significantlynegatively associated (OR 0.27, 95% CI 0.15-0.48; P&amp;lt;0.001) with&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;.Similar findings were observed when the analysis was repeated to include onlythose tests within 2 years of the resistance test. Effects for zidovudine andstavudine were evident only in an additional analysis, which consideredexposure to both drugs jointly within 2 years prior to the resistance test:exposure to zidovudine alone (OR 4.61, 95% CI 1.83-11.61; P&amp;lt;0.001) andexposure to stavudine alone (OR 3.39, 95% CI 1.32-8.71; P=0.011).&lt;span style="text-transform:uppercase"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;"&gt;CONCLUSIONS:&lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"&gt; &lt;/span&gt;&lt;span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"&gt;This is the first clinical evidence to suggest that efavirenz mightselect for&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;in addition to nevirapine, thatstavudine might select for&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;N348I&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;inaddition to zidovudine and that TDF might protect against the&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;mutation&lt;/span&gt;.&lt;span style="text-transform:uppercase"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;p class="MsoNoSpacing" style="text-align:justify"&gt;&lt;span lang="EN-US"&gt;&amp;nbsp;&lt;/span&gt;&lt;/p&gt;
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Asboe, D.
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Pozniak, A.
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Gazzard, B.
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Fearnhill, E.
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Pillay, D.
700 ## - ADDED ENTRY--PERSONAL NAME
Personal name Dunn, D.
710 ## - ADDED ENTRY--CORPORATE NAME
Corporate name or jurisdiction name as entry element UK Collaborative Group on HIV Drug Resistance
710 ## - ADDED ENTRY--CORPORATE NAME
Corporate name or jurisdiction name as entry element UK Collaborative HIV Cohort Study
856 ## - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://www.ncbi.nlm.nih.gov/pubmed/20386075">http://www.ncbi.nlm.nih.gov/pubmed/20386075</a>
856 ## - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="http://ferriman.wufoo.com/forms/r7x3a7/">http://ferriman.wufoo.com/forms/r7x3a7/</a>
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        Staff publications for NMDX Ferriman information and Library Service (North Middlesex) Ferriman information and Library Service (North Middlesex) Shelves 07/06/2022   07/06/2022 07/06/2022 Book
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