[48] Genotypic- and phenotypic-weighted OBT susceptibility scores are similarly strong predictors of virologic response <50 copies/ml at week 48 in MOTIVATE 1 and 2

18th International HIV Drug Resistance Workshop

Basic Principles & Clinical Implications

June 9–13 2009, Fort Myers, Florida, USA

GENOTYPIC- AND PHENOTYPIC-WEIGHTED OBT SUSCEPTIBILITY SCORES ARE SIMILARLY STRONG PREDICTORS OF VIROLOGIC RESPONSE <50 COPIES/ML AT WEEK 48 IN MOTIVATE 1 AND 2

Antivir Ther 2009; 14 Suppl 1:A52 (abstract no. 48)

C Boucher¹, JM Schapiro², D Kuritzkes³, JM Llibre⁴, M Lewis⁵, P Simpson⁵, C Delogne⁵, V Sharma⁶, A Parliyan⁶, D Chapman⁶, M Perros⁵, H Valdez⁶ and M Westby⁵
¹Utrecht University, Utrecht, the Netherlands; ²National Hemophilia Center, Tel Hashomer, Israel; ³Brigham and Women’s Hospital, Boston, MA, USA; ⁴Hospital Germans Trias i Pujol, Badalona, Spain; ⁵Pfizer Global R&D, Sandwich, UK; ⁶Pfizer, Inc, New York, NY, USA

OBJECTIVES: Separate analyses from the treatment-experienced MOTIVATE studies showed similar baseline predictors of virologic response to maraviroc plus optimized background therapy (OBT) in models using a weighted OBT sensitivity score (wOBTSS) based on phenotypic (p-wOBTSS) or genotypic (g-wOBTSS) resistance data. A comparison of phenotypic versus genotypic OBT scoring and MOTIVATE virologic response in a single population has been undertaken.

METHODS: Non-virologic failures, patients with OBT changes or non-simultaneous initiation of all agents, and those with missing resistance data were excluded from the MOTIVATE 1 and 2 full analysis set of 1,049 patients. P-wOBTSS was calculated from PhenoSense^™ (Monogram Biosciences) results and g-wOBTSS from the ANRS algorithm. Drugs continued from pre-randomization scored 0; newly initiated fully active NRTIs, 0.5; other fully active agents, 1.0; partially active PIs, 0.5 (g-wOBTSS only); and other partially active or inactive agents, 0. Virologic success was defined as <50 copies/ml at week 48. Success rates by treatment arm and p- and g-wOBTSS results were compared by Χ² and/or Fisher’s exact tests and logistic regression performed. Active drug combinations were investigated.

RESULTS: The analysis population was 598. Success rates in each treatment arm were very similar by p- and g-wOBTSS analyses. Patients with a wOBTSS =2 receiving OBT with placebo, once-daily maraviroc or twice-daily maraviroc had success rates of 52%, 70% and 73%, respectively, by p-wOBTSS and 57%, 72% and 71%, respectively, by g-wOBTSS (P=0.72, P=0.74, P=0.79). Similarly, for those with wOBTSS ≥2 and baseline CD4 count ≥50 cells/mm³, success rates were 55%, 80% and 81% (p-wOBTSS) and 62%, 79% and 77% (g-wOBTSS). Virologic failure with CXCR4-using virus was more common on maraviroc than placebo at wOBTSS <2, but similar to placebo at p-or g-wOBTSS ≥2. Tipranavir + enfuvirtide was the most common active drug combination (11%) in the g-wOBTSS ≥2 subset.

CONCLUSIONS: Weighted phenotypic and genotypic estimates of OBT activity are similarly predictive of undetectable viremia in MOTIVATE when applied to a defined population without on-treatment OBT changes. Approximately 80% of such patients with baseline CD4 ≥50 cells/mm³ initiating maraviroc with the equivalent of two fully active agents by either p-wOBTSS or g-wOBTSS had <50 RNA copies/ml at week 48.

2009-06-09
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