Short-term maraviroc exposure, a clinical approach to decide on maraviroc prescription in HIV-1-infected treatment-naïve patients

Abstract

Dear editor Woollard and Kanmogne1 have generated an exhaustive review on maraviroc and its use in human immunodeficiency virus (HIV) infection. Within their interesting dissertation, they discuss about the maraviroc clinical test (MCT), a clinical approach developed in our group in order to decide candidate patients to receive maraviroc as part of a further combined antiretroviral therapy, as an alternative to genotypic and phenotypic tropism assays.2 Based on our results, they state that MCT could help to determine/confirm the genotypic/phenotypic HIV-1 tropism, particularly in patients with nonreportable results by Trofile®. Subsequently, they note that “no concordance” between standard V3-based genotypic tropism assays and virological response to maraviroc monotherapy was found, according to previous results generated by our group.3 Finally, based on the results of Hernández-Novoa et al,4 they conclude that short-term maraviroc exposure cannot predict viral tropism in treatment-naïve patients. In our opinion, MCT is an alternative tool to be used in clinical practice to decide CCR5-antagonist prescription in HIV-infected subjects, both in treatment-experienced and -naïve patients. Discordances between phenotypic and genotypic methods have been found.5 Moreover, our group developed MCT, a drug sensitivity test but not a tropism assay, and again discordances between MCT and different tropism methods including deep-sequencing were found.5,6 Hence, it has not been established as a “gold standard” to be used in clinical practice before prescribing maraviroc. We consider that the virological response to the drug should be the most important criteria in order to decide maraviroc prescription, and not a categorical tropism result. Therefore, we use MCT not just to confirm a genotypic/phenotypic tropism result and not particularly in patients with a nonreportable result by Trofile® but in all patients. Regarding the naïve scenario, our group has explored this issue in a recently published work,7 confirming that MCT is a reliable tool to decide maraviroc prescription in naïve HIV-infected subjects. In this work, most patients showed a significant viral load reduction during MCT and an excellent immunovirological evolution was shown once the subsequent cART was started after MCT; again, discordance rates were found between MCT and different tropism methods, similar to those found in treatment-experienced patients.2,5,6 Unfortunately, the review by Woollard and Kanmogne1 was accepted for publication just before the publication of this work, so they probably did not have time to include our data in their study. Additionally, Woollard and Kanmogne consider that MCT cannot be used in naïve HIV-infected subjects based on data from Hernández-Novoa et al,4 because these authors concluded that this clinical test cannot be used as a surrogate marker of viral tropism in naïve patients. We agree with the conclusion of Hernández-Novoa et al, since MCT is not a surrogate marker of viral tropism but a clinical test based on the virological response to a short-term exposure to the drug, and provides discordant results with different tropism assays as previously reported.2,5,6 Hernández-Novoa et al show that patients with R5 or dual/mixed viral tropism according to Trofile® have similar virological responses to maraviroc monotherapy, reflecting the previously described discordance between the clinical approach and the phenotypic tropism method, as expected. Analyzing their data, we can see that 32/37 (85%) of their patients had virological response according to MCT (viral load reduction >1 log RNA copies/mL) while 5/37 (15%) did not, exactly the R5 and non-R5 expected percentages in HIV-1 treatment-naïve patients.8 In addition, given the MCT criteria, 9/37 (24%) of the patients had discordant results with Trofile® in their study, similar to previous studies.2,5–7 Besides, unlike Hernández-Novoa et al, in these mentioned studies we performed a follow-up of the patients proving the safety of the test according to the excellent immunovirological evolution after long-term cART started after MCT. Therefore, we consider that a misclassification by Trofile® and genotypic methods would be the more plausible explanation for the discordances observed with the virological response during maraviroc monotherapy exposure, probably due to the presence of low-level X4 variants with no clinical relevance. Taken altogether, we think that MCT remains a very promising strategy to decide maraviroc prescription in HIV-infected patients, both treatment-experienced and -naïve subjects, independent of the viral tropism result once the presence of low-level X4 variants seem to be clinically irrelevant.