Optimisation of baseline genotypic testing for safe and efficient maraviroc administration

Abstract

Different diagnostic parameters may affect the tropism prediction reliability. The impact of usage of FPR cut‐offs<20%, use of viral RNA versus proviral DNA samples, single versus triple amplification, and presence of MVC resistance mutations on tropism prediction at baseline were analysed on 101 patients receiving maraviroc (MVC) and correlated with their clinical outcome. This was a non‐interventional, retrospective study. 82 RNA and 54 DNA samples from the 101 patients receiving MVC were obtained. The V3 region was sequenced and the tropism predicted using the geno2pheno[coreceptor] and T‐CUP tools with FPR cut‐offs of 5%, 7.5%, 10%, 15% and 20%. Additionally, 27/82 RNA and 28/54 DNA samples were analysed in triplicate and 34/82 samples with the ESTA assay. The influence of 16 MVC resistance mutations on clinical outcome was studied. The genotypic susceptibility score (GSS) of the concomitant drugs was mapped to numerical values: susceptible to 1 (or 0.5 for NRTIs), intermediate to 0.5 (0.25 for NRTIs) and resistant to 0. Detection of baseline R5 viruses in RNA (by geno2pheno[coreceptor] and T‐CUP) or DNA (by T‐CUP) samples correlated with MVC‐treatment success. Both tools performed very similarly, with PPVs close to 90%, even with FPR cut‐offs as low as 5%. The use of triple amplification did not improve the prediction value but reduced the number of patients elegible for MVC treatment. No influence of the GSS or MVC resistance mutations on the clinical outcome was detected. Genotypic tropism testing from viral RNA and proviral DNA using the geno2pheno[coreceptor] and T‐CUP systems is valid to select candidates for MVC treatment. Our data suggest that the use of FPR cut‐offs of 5–7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this potent antiretroviral drug.