Background: Maraviroc-containing regimens are known to achieve virological suppression in many treatment-experienced patients. This study aimed to evaluate a more rigorous methodological approach to resistance-response analysis in large clinical studies and to better establish which subpopulations of patients were most likely to benefit from maraviroc by refining and extending previous subgroup analyses from the MOTIVATE studies. Methods: Individual weighted optimized background therapy (OBT) susceptibility scores were calculated by combining genotypic or phenotypic resistance testing with prior drug use information. Virological response (HIV-1 RNA<50 copies/ml at week 48) using each of these methods was compared with a commonly used method of counting active drugs. Baseline predictors of virological response, including weighted or unweighted scoring, maraviroc use, baseline CD4+T-cell count, HIV-1 plasma viral load and tropism, were assessed by logistic regression modelling. Results: Genotypic or phenotypic weighted methods were similarly predictive of virological response and better than counting active drugs. Weighted scoring and baseline CD4+T-cell count were the strongest predictors of virological response (P<0.0001): ≈70% of maraviroc patients with a weighted score ≥2 had a virological response, rising to ≈80% when the baseline CD4+T-cell count was ≥50 cells/mm3. Conclusions: Approximately 80% of patients with a CD4+T-cell count ≥50 cells/mm3receiving maraviroc with the equivalent of at least two fully active agents achieved HIV-1 RNA<50 copies/ml at week 48 in the MOTIVATE studies. Genotypic and phenotypic weighted scores were similarly predictive of virological response.

doi.org/10.3851/IMP1759, hdl.handle.net/1765/26599
Antiviral Therapy
Erasmus MC: University Medical Center Rotterdam

Schapiro, J., Boucher, C., Kuritzkes, D., van de Vijver, D., Llibre, J. M., Lewis, C., … Westby, M. (2011). Baseline CD4+ T-cell counts and weighted background susceptibility scores strongly predict response to maraviroc regimens in treatment-experienced patients. Antiviral Therapy, 16(3), 395–404. doi:10.3851/IMP1759