[ThOrB1390] Expanded response analyses of tenofovir DF Therapy by Baseline Resistance Genotype and Phenotype

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Expanded response analyses of tenofovir DF Therapy by Baseline Resistance Genotype and Phenotype

[AUTHOR(S):] N A Margot¹, A K Cheng², B Lu³, M D Miller⁴

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. ThOrB1390

BACKGROUND: Studies 902 and 907 were placebo-controlled studies evaluating tenofovir DF (TDF) when added to stable regimens in patients (pts) with incomplete HIV RNA suppression. At wk 24, the placebo (PLB) arms crossed over to TDF 300 mg.

METHODS: In virology substudies, baseline (BL) plasma HIV genotypes (n=332) and phenotypes (n=138, Antivirogram) from pts randomized to PLB or TDF 300 mg were obtained. Analyses were expanded to include wk24 plasma samples as BL for PLB cross-over (PLB CO) pts (n=103).

RESULTS: TDF therapy resulted in significant mean HIV RNA reductions from BL to wk24 (-0.59 log) that were notably durable through wk48 (-0.56 log). At wk24, significant HIV RNA reductions relative to PLB (p<0.001) were observed for pts without TAMs (-0.80 log, n=97) or with 1-2 TAMs (-0.66 log, n=88). For ≥3 TAMs with M41L or L210W, responses were diminished (-0.21 log, n=86) but superior to PLB (p=0.013); pts with ≥3 TAMs without M41L or L210W had -0.67 log responses (n=61, p<0.001). From wk 24-48, the PLB CO pts had an HIV RNA decrease of -0.65 log. The PLB CO pts confirmed the genotypic response patterns observed from TDF pts. Of note, PLB CO pts with L74V or Q151M had responses of -0.59 log (n=15) and -0.86 log (n=2). Combined phenotypes from BL (TDF) or wk24 (PLB CO) showed mean reduced susceptibility of 1.8-fold for TDF (n=204, range 0.1-11). 24 wk response for pts with <1 (n=79), 1-2 (n=66), 2-3 (n=27) and 3-4 (n=13) fold changes in TDF susceptibility were -0.84, -0.61, -0.58 and -0.40 logs. Pts with >4-fold reductions in TDF susceptibility (n=19, 9%) showed diminished responses of -0.22 log. Recursive partitioning analysis confirmed a 4-fold cut-off for response to TDF therapy.

CONCLUSIONS: Adding tenofovir DF once-daily to an existing regimen showed significant and durable HIV RNA reductions. Reduced responses to TDF treatment were associated with multiple TAM patterns inclusive of M41L or L210W, or >4-fold reduced susceptibility to TDF.

Presenting author: M D Miller

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1Gilead Sciences, Foster City, United States

2Gilead Sciences, Foster City, United States

3Gilead Sciences, Foster City, United States

4Gilead Sciences, Foster City, United States

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ThOrB1390