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Long term probability of detecting HIV drug resistance in drug-naïve patients starting non nucleoside reverse transcriptase inhibitor- or ritonavir boosted protease inhibitor- containing antiretroviral therapy.

By: Contributor(s): Publication details: 2010ISSN:
  • 10584838
Uniform titles:
  • Clinical infectious diseases
Online resources: Summary: <br /><div style="line-height: 17.999801635742188px;"><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">BACKGROUND:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">METHODS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance.</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">RESULTS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, > or =1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, > or =1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and > or =1 major PI IAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a PI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P=.98).</span></p><h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"><span style="font-size: 8pt;">CONCLUSIONS:</span></h4><p style="margin: 0px 0px 0.5em;"><span style="font-size: 8pt;">In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.</span></p></div>
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&lt;br /&gt;&lt;div style="line-height: 17.999801635742188px;"&gt;&lt;h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"&gt;&lt;span style="font-size: 8pt;"&gt;BACKGROUND:&lt;/span&gt;&lt;/h4&gt;&lt;p style="margin: 0px 0px 0.5em;"&gt;&lt;span style="font-size: 8pt;"&gt;Robust long-term estimates of the risk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infected patients starting combination antiretroviral therapy (cART) regimens currently used in routine clinical practice.&lt;/span&gt;&lt;/p&gt;&lt;h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"&gt;&lt;span style="font-size: 8pt;"&gt;METHODS:&lt;/span&gt;&lt;/h4&gt;&lt;p style="margin: 0px 0px 0.5em;"&gt;&lt;span style="font-size: 8pt;"&gt;We followed a large cohort of patients seen in 1 of 11 HIV clinics in the United Kingdom after starting cART with nucleoside reverse-transcriptase inhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis was employed to estimate the incidence of virological failure and of detected drug resistance.&lt;/span&gt;&lt;/p&gt;&lt;h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"&gt;&lt;span style="font-size: 8pt;"&gt;RESULTS:&lt;/span&gt;&lt;/h4&gt;&lt;p style="margin: 0px 0px 0.5em;"&gt;&lt;span style="font-size: 8pt;"&gt;Seven thousand eight hundred ninety-one patients were included; 6448 (82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, &amp;gt; or =1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, &amp;gt; or =1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and &amp;gt; or =1 major PI IAS-USA mutation (in those starting a PI) were 17%, 14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PI mutations in people who started PI/r-based regimens was lower than that of detecting NNRTI mutations in those starting NNRTI-based regimens (adjusted relative hazard, 0.36; 95% confidence interval, 0.26-0.50; P&amp;lt;.001). The risk of detecting nucleoside resistance did not vary according to whether an NNRTI or a PI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P=.98).&lt;/span&gt;&lt;/p&gt;&lt;h4 style="margin: 0px 0.25em 0px 0px; text-transform: uppercase; float: left;"&gt;&lt;span style="font-size: 8pt;"&gt;CONCLUSIONS:&lt;/span&gt;&lt;/h4&gt;&lt;p style="margin: 0px 0px 0.5em;"&gt;&lt;span style="font-size: 8pt;"&gt;In patients who started modern cART in clinical practice in the United Kingdom, virological failure by 8 years was relatively common and was paralleled by an appreciable risk of resistance detection, although the detection rate of class-specific resistance was lower for those who started a PI/r-based regimen.&lt;/span&gt;&lt;/p&gt;&lt;/div&gt;

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