| 000 | 06332cam a2200277 4500 | ||
|---|---|---|---|
| 001 | NMDX5902 | ||
| 008 | 120401t2010 xxu||||| |||| 00| 0 eng d | ||
| 022 | _a13596535 | ||
| 100 | _aPrice, H. | ||
| 240 | _aAntiviral Therapy | ||
| 245 | _aPositive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data | ||
| 260 | _c2010 | ||
| 500 | _aNMUH Staff Publications | ||
| 500 | _a15 | ||
| 520 | _a<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 | _aAsboe, D. | ||
| 700 | _aPozniak, A. | ||
| 700 | _aGazzard, B. | ||
| 700 | _aFearnhill, E. | ||
| 700 | _aPillay, D. | ||
| 700 | _aDunn, D. | ||
| 710 | _aUK Collaborative Group on HIV Drug Resistance | ||
| 710 | _aUK Collaborative HIV Cohort Study | ||
| 856 | _uhttp://www.ncbi.nlm.nih.gov/pubmed/20386075 | ||
| 856 | _uhttp://ferriman.wufoo.com/forms/r7x3a7/ | ||
| 999 |
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