18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

WEEK 48 RESULTS FROM THE PHASE III STUDY A4001026 (MERIT) – ‘TIME TO LOSS OF VIROLOGIC RESPONSE’ (TLOVR) VIROLOGY ANALYSIS OF FAILURES IN THE ENHANCED TROFILE^™-CENSORED SUBPOPULATION

Antivir Ther 2009; 14 Suppl 1:A50 (abstract no. 46)

C Craig¹, M Lewis¹, P Simpson¹, C Delogne¹, E van der Ryst¹, J Heera², J Goodrich², M Perros¹ and M Westby^1
1Pfizer Global R&D, Sandwich, UK; ²Pfizer Global R&D, New London, CT, USA

OBJECTIVES: Post-hoc analysis of study A4001026 (MERIT) using an enhanced sensitivity tropism assay (Trofile™-ES) demonstrated similar week 48 virologic responses in treatment-naïve subjects with CCR5-tropic (R5) HIV-1 receiving maraviroc (MVC) 300 mg twice daily + Combivir^® (CBV) compared with efavirenz (EFV) 600 mg once daily + CBV (n=311 and 303, respectively). Genotypic and phenotypic changes during 48 weeks of therapy were investigated in the TLOVR failure subpopulation.

METHODS: Subjects were identified who experienced virologic failure (VF) or discontinued therapy for other reasons after ≥28 days with viral load (VL) >50 copies/ml at week 48 or the last time point with VL data on study drug. For subjects with VL >500 copies/ml at the time of failure (week 48, time of virologic rebound or time of discontinuation), plasma HIV-1 RNA was assessed for RT genotype (PhenoSense GT^™) and MVC phenotype (PhenoSense Entry^®); post-screening tropism was determined using the original Trofile assay. Only subjects with complete datasets were included in the analysis.

RESULTS: At week 48, 30 and 17 subjects in the MVC and EFV treatment arms, respectively, met the criteria described above. Resistance-associated mutations (RAMs) were absent at failure in 15/30 (50%) MVC-treated and 7/17 (41%) EFV-treated subjects. For the remaining subjects, the predominant resistance markers were M184V for MVC (15/30, 50%) and NNRTI RAMs for EFV (9/17, 53%). With MVC, CXCR4-using virus was detected at failure in 8/30 (27%) subjects and MVC-resistant R5 virus was detected in 4/30 (13%) subjects; in all instances, M184V was also present. Thymidine analogue mutations (TAMs) were present at failure in 4/30 (13%) MVC-treated subjects. For EFV-treated subjects, 4/17 (24%) had NNRTI RAMs with M184V or a TAM; 1/17 (6%) had M184V alone.

CONCLUSIONS: The presence of an M184V mutation was most commonly associated with virologic failure in MVC-treated subjects (50%), whereas EFV failure was most commonly associated with NNRTI RAMs (53%). As with treatment-experienced MVC-treated subjects, emergence of CXCR4-using virus (27%) or reduced susceptibility of R5 virus (13%) was observed. Resistance was not observed in approximately half of MVC-treated (50%) and EFV-treated subjects analysed (41%).

2009-06-09
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