Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study

TitleTime trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study
Publication TypeJournal Article
Year of Publication2012
AuthorsDolling D, Sabin CA, Delpech V, Smit E, Pozniak A, Asboe D, Leigh Brown A, Churchill D, Williams I, Geretti AM, Phillips AN, Mackie N, Murphy G., Castro H, Pillay D, Cane P A, Dunn DT, Dolling D
JournalBMJ
Volume345
Paginatione5253
Date Published2012-08
ISBN Number0959-535x
Accession Number22915687
Keywords*Anti-Retroviral Agents/pharmacology/therapeutic use, Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Drug Resistance, Viral/*genetics, Female, Great Britain/epidemiology, HIV Infections/drug therapy/epidemiology/*virology, HIV-1/drug effects/*genetics, Humans, Linear Models, Logistic Models, Male, Microbial Sensitivity Tests, Middle Aged, Mutation Rate, Prevalence, Young Adult
Abstract

OBJECTIVE: To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom. DESIGN: Multicentre observational study. SETTING: All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care. PARTICIPANTS: 14,584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009. MAIN OUTCOME MEASURE: Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization. RESULTS: 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively). CONCLUSIONS: The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.

Short TitleBMJ (Clinical research ed.)
Alternate JournalBMJ (Clinical research ed.)