Long-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy

By:

Cozzi-Lepri, A

Contributor(s):

Publication details: 2010ISSN:

10584838

Uniform titles:

Clinical Infectious Diseases

Online resources:

Summary: BACKGROUND: Robust long-term estimates of therisk of development of drug resistance are needed for human immunodeficiency virus (HIV)-infectedpatients starting combination antiretroviral therapy (cART) regimens currentlyused in routine clinical practice.METHODS: 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 drug resistance.RESULTS: 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 mutation,> or =1 major nucleoside reverse-transcriptase inhibitor International AIDSSociety-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 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).CONCLUSIONS: 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.

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BACKGROUND: Robust long-term estimates of therisk of development of&nbsp;drug&nbsp;resistance are needed for human immunodeficiency virus (HIV)-infectedpatients starting combination antiretroviral therapy (cART) regimens currentlyused in routine clinical practice.METHODS: 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&nbsp;drug&nbsp;resistance.RESULTS: 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&nbsp;mutation,&gt; or =1 major nucleoside reverse-transcriptase inhibitor International AIDSSociety-United States of America (IAS-USA)&nbsp;mutation, &gt; or =1 major NNRTI IAS-USA&nbsp;mutation&nbsp;(in those starting an NNRTI), and&gt; or =1 major PI IAS-USA&nbsp;mutation&nbsp;(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&lt;.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).CONCLUSIONS: 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.

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