Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data (Record no. 75400)
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000 -LEADER | |
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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. | <h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"><span lang="EN-US" style="font-size: 7.5pt;">BACHGROUND:</span><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;"> There is conflicting evidence onspecific reverse transcriptase inhibitors to which the&nbsp;N348I&nbsp;mutation&nbsp;inthe&nbsp;connection&nbsp;domain&nbsp;of HIV type-1 reverse transcriptaseconfers resistance. Here, we examined associations between the emergence of&nbsp;N348I&nbsp;andantiretroviral history in a large clinical database.</span></h4><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;"><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;">METHODS:</span><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"> </span><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;">We analysed 5,353 resistance tests (that were sequenced beyond codon 348)among 2,266 antiretroviral-experienced patients. Associations between<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span><span class="apple-converted-space">&nbsp;</span>and individual antiretroviral<span class="apple-converted-space">&nbsp;</span><span class="highlight">drug</span><span class="apple-converted-space">&nbsp;</span>exposure were estimated using amatched case-control approach. Cases were defined as the first resistance testwhere<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span><span class="apple-converted-space">&nbsp;</span>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.<span style="text-transform:uppercase"></span></span></h4><h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;">RESULTS:</span><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"> </span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;">N348I</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;">&nbsp;</span></span><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;">was detected in 198 (8.7%)cases. Drugs that were statistically significantly positively associated with<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span><span class="apple-converted-space">&nbsp;</span>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&lt;0.001). Tenofovir disoproxil fumarate (TDF) was significantlynegatively associated (OR 0.27, 95% CI 0.15-0.48; P&lt;0.001) with<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span>.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&lt;0.001) andexposure to stavudine alone (OR 3.39, 95% CI 1.32-8.71; P=0.011).<span style="text-transform:uppercase"></span></span></h4><h4 style="margin: 0cm 3pt 0.0001pt 0cm; text-align: justify; line-height: 9.8pt; background-position: initial initial; background-repeat: initial initial;"><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase;">CONCLUSIONS:</span><span lang="EN-US" style="font-size: 7.5pt; text-transform: uppercase; font-weight: normal;"> </span><span lang="EN-US" style="font-size: 7.5pt; font-weight: normal;">This is the first clinical evidence to suggest that efavirenz mightselect for<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span><span class="apple-converted-space">&nbsp;</span>in addition to nevirapine, thatstavudine might select for<span class="apple-converted-space">&nbsp;</span><span class="highlight">N348I</span><span class="apple-converted-space">&nbsp;</span>inaddition to zidovudine and that TDF might protect against the<span class="apple-converted-space">&nbsp;</span><span class="highlight">mutation</span>.<span style="text-transform:uppercase"></span></span></h4><p class="MsoNoSpacing" style="text-align:justify"><span lang="EN-US">&nbsp;</span></p> |
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> |
Withdrawn status | Lost status | Damaged status | Not for loan | Collection code | Home library | Current library | Shelving location | Date acquired | Total Checkouts | Date last seen | Price effective from | Koha item type |
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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 |