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

Cozzi Lepri Alesandro, David Dunn, Deenan Pillay, Caroline A. Sabin, Esther Fearnhill, Anna Maria Gerettsabini, Teresa Hill, Steve Kaye, Loveleen Bansi, Erasmus Smit, Margaret Johnson, Sheila Burns, Richard Gilson, Sheila Cameron, Philippa Easterbrook, Mark Zuckerman, Brian Gazzard, John Walsh, Martin Fisher, Chloe OrkinJonathan Ainsworth, Clifford Leen, Mark Gompels, Jane Anderson, Andrew N. Phillips, Abdel Babiker, Kholoud Porter, Tariq Sadiq, Achim Schwenk, Nicky Mackie, Alan Winston, Valerie Delpech, David Asboe, Anton Pozniak, Patricia Cane, Porton Down, Duncan Churchill, Duncan Clark, Linda Lazarus, Hannah Green, Paul Kellam, David Goldberg, Antony Hale, Svilen Konov, Andrew Leigh-Brown, Nicola Mackie, Peter Tilston, Ian Williams, Hongyi Zhang, Adam Glabay

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38 Citations (Scopus)

Abstract

Background. 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. Methods. 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. 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 cumulative risk of virological failure by 8 years was 28%. The cumulative probabilities of detecting any mutation, ≥ 1 major nucleoside reverse-transcriptase inhibitor International AIDS Society-United States of America (IAS-USA) mutation, ≥ 1 major NNRTI IAS-USA mutation (in those starting an NNRTI), and ≥ 1 major PIIAS-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 Pl/r was used in the regimen (adjusted relative hazard, 1.00; 95% confidence interval, 0.80-1.26; P = .98). Conclusions. 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.

Original languageEnglish
Pages (from-to)1275-1285
Number of pages11
JournalClinical Infectious Diseases
Volume50
Issue number9
DOIs
Publication statusPublished - 1 May 2010

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