Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy
Cozzi-Lepri, A.
Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy - 2010
NMUH Staff Publications 50
<p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US">BACKGROUND:</span></strong><span lang="EN-US"> Robust long-term estimates of therisk of development of</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">drug</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">resistance are needed for human immunodeficiency virus (HIV)-infectedpatients starting combination antiretroviral therapy (cART) regimens currentlyused in routine clinical practice.</span></p><p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">METHODS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">We followed a large cohort of patients seen in 1 of 11 HIV clinics inthe United Kingdom after starting cART with nucleoside reverse-transcriptaseinhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI)or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis wasemployed to estimate the incidence of virological failure and of detected</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">drug</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">resistance.<span style="text-transform:
uppercase"></span></span></p><p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">RESULTS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">Seven thousand eight hundred ninety-one patients were included; 6448(82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulativerisk of virological failure by 8 years was 28%. The cumulative probabilities ofdetecting any</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span lang="EN-US">,> or =1 major nucleoside reverse-transcriptase inhibitor International AIDSSociety-United States of America (IAS-USA)</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span lang="EN-US">, > or =1 major NNRTI IAS-USA</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">(in those starting an NNRTI), and> or =1 major PI IAS-USA</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">(in those starting a PI) were 17%,14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PImutations in people who started PI/r-based regimens was lower than that of detectingNNRTI mutations in those starting NNRTI-based regimens (adjusted relativehazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk ofdetecting nucleoside resistance did not vary according to whether an NNRTI or aPI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidenceinterval, 0.80-1.26; P=.98).<span style="text-transform:uppercase"></span></span></p><p class="MsoNormal" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">CONCLUSIONS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">In patients who started modern cART in clinical practice in the UnitedKingdom, virological failure by 8 years was relatively common and wasparalleled by an appreciable risk of resistance detection, although thedetection rate of class-specific resistance was lower for those who started aPI/r-based regimen.<span style="text-transform:uppercase"></span></span></p>
10584838
Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy - 2010
NMUH Staff Publications 50
<p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US">BACKGROUND:</span></strong><span lang="EN-US"> Robust long-term estimates of therisk of development of</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">drug</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">resistance are needed for human immunodeficiency virus (HIV)-infectedpatients starting combination antiretroviral therapy (cART) regimens currentlyused in routine clinical practice.</span></p><p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">METHODS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">We followed a large cohort of patients seen in 1 of 11 HIV clinics inthe United Kingdom after starting cART with nucleoside reverse-transcriptaseinhibitors and either a nonnucleoside reverse-transcriptase inhibitor (NNRTI)or a ritonavir-boosted protease inhibitor (PI/r). Survival analysis wasemployed to estimate the incidence of virological failure and of detected</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">drug</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">resistance.<span style="text-transform:
uppercase"></span></span></p><p class="MsoNoSpacing" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">RESULTS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">Seven thousand eight hundred ninety-one patients were included; 6448(82%) started cART with an NNRTI and 1423 (17%) with a PI/r. The cumulativerisk of virological failure by 8 years was 28%. The cumulative probabilities ofdetecting any</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span lang="EN-US">,> or =1 major nucleoside reverse-transcriptase inhibitor International AIDSSociety-United States of America (IAS-USA)</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span lang="EN-US">, > or =1 major NNRTI IAS-USA</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">(in those starting an NNRTI), and> or =1 major PI IAS-USA</span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span class="highlight"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;">mutation</span></span><span class="apple-converted-space"><span lang="EN-US" style="font-size: 7.5pt; font-family: Arial, sans-serif;"> </span></span><span lang="EN-US">(in those starting a PI) were 17%,14%, 15%, and 7%, respectively, by 8 years. The probability of detecting PImutations in people who started PI/r-based regimens was lower than that of detectingNNRTI mutations in those starting NNRTI-based regimens (adjusted relativehazard, 0.36; 95% confidence interval, 0.26-0.50; P<.001). The risk ofdetecting nucleoside resistance did not vary according to whether an NNRTI or aPI/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidenceinterval, 0.80-1.26; P=.98).<span style="text-transform:uppercase"></span></span></p><p class="MsoNormal" style="text-align:justify"><strong><span lang="EN-US" style="text-transform:uppercase;mso-ansi-language:
EN-US">CONCLUSIONS:</span></strong><span lang="EN-US" style="text-transform:uppercase;
mso-ansi-language:EN-US"> </span><span lang="EN-US">In patients who started modern cART in clinical practice in the UnitedKingdom, virological failure by 8 years was relatively common and wasparalleled by an appreciable risk of resistance detection, although thedetection rate of class-specific resistance was lower for those who started aPI/r-based regimen.<span style="text-transform:uppercase"></span></span></p>
10584838