Factors associated with virological success with raltegravir-containing regimens and prevalence of raltegravir-resistance-associated mutations at failure in the ARCA database

Raltegravir (RAL) is the only licensed HIV integrase inhibitor. The factors associated with virological response to RAL-containing regimens and the prevalence of integrase mutations associated to RAL failure deserve further investigation.From the ARCA database, we selected 3-class experienced subjects failing their current treatment with complete treatment history available. Selection criteria included HIV-RNA, CD4 count and HIV genotype within 3 months prior to RAL initiation. Factors associated with 24-week response were analyzed; genotypic sensitivity scores (GSS) and weighted-GSS were evaluated.Virological response was achieved in 74.3% of 105 subjects. Mutations associated to RAL failure were detected in 12/24 subjects with an IN genotype, with the prevalence of Q148H+G140S. Each extra unit of GSS (p=.05, OR 2.62 [95% CI 1.00-6.87]). was found to be a associated with response. Weighted-GSS had borderline statistical significance (p=.063, OR 2.04 [95% CI 0.96-4.33]) When stratifying for different cut-offs (<1 as reference, 1-1.49, ≥1.5), a borderline significant increase in the probability of response appeared for GSS ≥1.5 (p=.053, OR 4.00 [95% CI 0.98-16.25]). GSS≥1 showed the highest sensitivity, 82.6%. ROC curves depicted the widest AUC (0.663, p=.054) of GSS ≥1.Unresponsiveness to RAL-containing regimens among 3-class experienced subjects was low. The activity of the background regimen was strongly associated with response. Although few IN genotypes were available at failure, half of these were without IN resistance mutations. The substantial rate of RAL failure in the absence of known RAL-resistance mutations may be associated with adherence issues and this issue warrants further analysis in longer observations.