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High Rates of Viral failure/Resistance to HAART-need for new drugs
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"Risk of development of drug resistance in patients startingantiretroviral therapy with three or more drugs in routine clinicalpractice"
ABSTRACT 135
Antiviral Therapy 2004; 9:S151.
AN Phillips1, D Dunn2, C Sabin1, A Pozniak3, R Matthias2, AM Geretti4, J Clarke5, D Churchill6, I Williams1,7, T Hill1, H Green2, K Porter2, G Scullard5, M Johnson4, P Easterbrook8, R Gilson1,7, M Fisher6,C Loveday9, B Gazzard3 and D Pillay1, for the UK HIV Drug Resistance Database and UK CHIC Groups
1 Royal Free and University College Medical School, London; 2 Medical Research Council Clinical Trials Unit, London; 3 Chelsea and Westminster Hospital; 4 Royal Free Hospital NHS Trust; 5 St Mary's Hospital and Imperial College School of Medicine; 6 Brighton and Sussex University Hospitals; 7 Mortimer Market Centre, Camden Primary Care NHS Trust; 8 King's CollegeHospital, London; and 9 ICVC, Bucks, UK
BACKGROUND: At a population level, durability of the benefit received from the currently available classes of antiretrovirals depends largely on the rate with which resistance mutations occur in patients in routine practice who started antiretroviral (ART) therapy with >=3 drugs.
METHODS: We assembled information on resistance tests performed as part of routine care on patients starting ART with >=3 drugs who were seen in one of six clinics in London/Brighton.
RESULTS: 4496 patients started ART with >=3 drugs 1996--2003. 56% started with an NNRTI, 41% with a protease inhibitor. The cumulative risk of virologicalfailure (two viral load >1000 copies/ml after 24 weeks from start of ART, unless during interruption) was 24% by 2 years, 34% by 4 years and 42% by 6 years.
707 patients (16%) had a resistance test result at some time after start of ART. 559 (47%) of the patients with virological failure had a resistance result (314 [56%] by 6 months after first virological failure), while 148 (4%)of those not fulfilling the virological failure definition had a resistance result.
Risk of >=1 major IAS USA mutation among the whole 4496 patients was 9% by 2years, 21% by 4 years and 30% by 6 years.
Risks by 6 years for class-specific mutations were: M184V/I 18%, >=1 TAM 15%, NNRTI 17% (25% when restricted to those who started with NN), major protease mutation 8% (10% when restricted to those who started with aPI).
Corresponding figures for accumulating >=1 mutation from each of the three main drug classes were 1% by 2 years, 2.5% by 4 years and 3.5% by 6 years. These are lower limit estimates as test results were not available for many with virological failure, and resistance below sensitivity limits of assays will be missed. Factors presented in poster.
CONCLUSION: In routine practice, rates of virological failure and of resistance development in patients who started ART with three or more drugs are appreciable, emphasizing the need for new antiretroviralsover the coming years.
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