Journal Article

Long-Term Probability of Detecting Drug-Resistant HIV in Treatment-Naive Patients Initiating Combination Antiretroviral Therapy

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 9, pages 1275-1285
Published in print May 2010 | ISSN: 1058-4838
Published online May 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/651684
Long-Term Probability of Detecting Drug-Resistant HIV in Treatment-Naive Patients Initiating Combination Antiretroviral Therapy

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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 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).

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.

Journal Article.  5667 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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