[O10] PATTERNS OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) GENOTYPIC AND PHENOTYPIC RESISTANCE IN PATIENTS INFECTED WITH EITHER B OR NON-B HIV-1 SUBTYPES AND FAILING THERAPY WITH TWO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS) AND NEVIRAPINE (NVP)

7th Annual Conference Of The British HIV Association [BHIVA]

27 – 29 April 2001, The Hove Centre, Brighton

[TITLE:] PATTERNS OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI) GENOTYPIC AND PHENOTYPIC RESISTANCE IN PATIENTS INFECTED WITH EITHER B OR NON-B HIV-1 SUBTYPES AND FAILING THERAPY WITH TWO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS) AND NEVIRAPINE (NVP)

[AUTHOR(S):] AM Geretti^1,2, M Smith², N Osner², BA Larder³, M Zuckerman², PJ Easterbrook¹
¹ Academic Department of HIV Medicine and ² Department of Virology, GKT School of Medicine, King’s College, London, and ³ Virco, Cambridge, UK

BHIVA Conf 2001 Apr 27-29;7:O10

OBJECTIVE: To determine the prevalence and patterns of NNRTI resistance in patients failing therapy with NVP and two NRTIs.

METHODS: Eligibility: plasma viral load >1000 copies/ml after >3 months of two NRTIs plus NVP; naïve to other NNRTIs. Genotypes were determined by TrueGene (Visible Genetics) or VircoGEN (Virco). Phenotypes were determined by the Antivirogram (Virco) recombinant virus assay.

RESULTS: Genotypes were obtained in 51/60 patients, including 25 B and 26 non-B subtypes, equally distributed between treatment arms; 37 patients (19 B and 18 non-B) had NNRTI resistance mutations and 32 of these also had NRTI resistance mutations. The most common NNRTI mutations were Y181C (51%) and K103N (43%). Of the 19 B subtypes with NNRTI mutations, 58% had K103N and 37% Y181C. Of the 18 non-B subtypes with NNRTI mutations, 17% had K103N and 67% Y181C. No significant differences in the prevalence of K103N and Y181C were detected between treatment arms. In particular, of the patients on ZDV, 25% had K103N and 42% Y181C. Of the patients not receiving ZDV, 46% had K103N and 50% Y181C. Other NNRTI mutations were G190A/S (22%), V108I and K101E/Q (14%), A98G and V106A (8%), V179D and Y188C/L (5%). Phenotypes from 17 patients correlated with genotypes; thus, the large majority of NNRTI resistance mutation patterns confer high-level resistance to all available NNRTIs.

CONCLUSIONS: Y181C was more prevalent than K103N for non-B. ZDV+NVP did not favour the emergence of K103N over Y181C.

PRESENTING AUTHOR: AM Geretti

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