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

TitleLong-term probability of detecting drug-resistant HIV in treatment-naive patients initiating combination antiretroviral therapy
Publication TypeJournal Article
Year of Publication2010
AuthorsUK Collaborative Group on HIV Drug Resistance, UK Collaborative HIV Cohort Study(UK CHIC)
JournalClin Infect Dis
Volume50
Pagination1275-85
Date PublishedMay 1
ISBN Number1058-4838
Accession Number20353366
Keywords*Antiretroviral Therapy, Highly Active, *Drug Resistance, Viral, Adolescent, Adult, Aged, Aged, 80 and over, Anti-HIV Agents/*therapeutic use, Female, Great Britain, HIV Infections/*drug therapy/*virology, HIV/*drug effects/isolation & purification, Humans, Male, Middle Aged, Prevalence, Survival Analysis, Treatment Failure, Young Adult
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, > 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). 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.

Short TitleClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Alternate JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America