|
Virologic suppression on maraviroc in treatment-naïve patients with R5 HIV-1 is similar to efavirenz at high baseline viral load, and maraviroc discontinuations for adverse events are less likely to show drug resistance: 48-week results from the MERI
M. Nelson1, A. Lazzarin2, G. Di Perri3, R. Campo4, R. Wood5, J. Goodrich6, J. Heera6, E. van der Ryst7, H. Mayer6, M. Tawadrous6, C. Craig7, M. Westby7
1Chelsea and Westminster Hospital, London, United Kingdom, 2San Raffaele Scientific Institute, Milan, Italy, 3University of Turin, Turin, Italy, 4University of Miami, Miami, United States, 5University of Cape Town, Cape Town, South Africa, 6Pfizer Global Research and Development, New London, United States, 7Pfizer Global Research and Development, Sandwich, United Kingdom
Background: Post hoc reanalysis of the MERIT study (MERIT-ES) using a more sensitive screening tropism assay has shown similar week 48 virologic responses in treatment-naïve patients with R5 HIV-1 who received twice-daily maraviroc (MVC) + Combivir® (CBV) to those receiving efavirenz (EFV) + CBV, but with fewer MVC discontinuations for adverse events (AEs).
Methods: Subgroup analyses of week 48 virologic response by baseline randomization strata
(< 105 vs ≥ 105 HIV-1 RNA copies/mL; Northern vs Southern hemisphere recruitment) were undertaken for the MERIT and MERIT-ES datasets. Virologic response on EFV and MVC (MERIT only) were compared for patients who discontinued through 48 weeks for adverse events, along with time to discontinuation and associated HIV-1 drug resistance.
Results: Subgroup results are shown below.
| < 50 HIV-1 RNA copies/mL at week 48 (ITT) | MERIT | MERIT-ES | | | EFV | MVC | EFV | MVC | | Baseline ≥ 105 copies/mL | 99/150
(66.0%) | 93/156
(59.6%) | 75/120 (62.5%) | 86/134 (64.2%) | | Baseline < 105 copies/mL | 151/211 (71.6%) | 142/204 (69.6%) | 132/183 (72.1%) | 127/177 (71.8%) | | Northern hemisphere | 135/199 (67.8%) | 132/194
(68.0%) | 106/162 (65.4%) | 118/164 (72.0%) | | Southern hemisphere | 115/162 (71.0%) | 103/166 (62.1%) | 101/141 (71.6%) | 95/147 (64.6%) |
EFV discontinuations due to AEs (DAEs) were 3-fold higher than on MVC (13.6% [49/361] vs 4.2% [15/360]), occurred earlier (78.0% by week 16 vs 60.0%) and were more viremic (≥ 50 copies/mL) before discontinuation (69.0% vs 60.0%). After drug withdrawal, 7/49 (14.3%) EFV DAEs developed new EFV-associated mutations. No outgrowth of CXCR4-using virus occurred for MVC DAEs.
Conclusions: Relative to MERIT, the MERIT-ES reanalysis showed improved MVC responses at week 48 across randomization strata, particularly for those with high baseline viral load. EFV DAEs were less likely to be suppressed before drug withdrawal and more likely to be associated with the development of drug resistance.
Download the e-Poster
|