Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study

Novel nucleoside reverse transcriptase inhibitor- and protease inhibitor-sparing strategies are needed in long-term-treated patients with lipohypertrophy. Given their potency and their excellent metabolic profile, maraviroc and raltegravir appear to be good candidates for such an approach. This single-arm study enrolled lipohypertrophic HIV-infected patients with suppressed viraemia and an R5 tropic virus in HIV DNA; they switched from suppressive antiretroviral treatment to maraviroc plus raltegravir. The primary endpoint was the proportion of patients with treatment success at week 24, defined as no virological failure or treatment discontinuation. To ensure a success rate of at least 80%, a maximum of 10 failures were allowed for 90 patients enrolled. ClinicalTrials.gov: NCT01420523. A total of 44 patients were enrolled; their median age was 55 years, median nadir CD4 cell count was 210 cells/mm(3), median time on antiretroviral treatment was 15 years and median duration of viral suppression was 5.2 years. Seven patients failed maraviroc/raltegravir therapy: five had virological failure and two discontinued treatment due to serious adverse events (one had hepatitis B virus reactivation and one had hypersensitivity syndrome). At failure, raltegravir resistance mutations were detected in 3/5 patients and CXCR4 tropic virus in 2/5. Upon DSMB recommendation, the study was prematurely discontinued on 3 September 2012. Lipid profile and bone mineral density improved with a decrease from baseline values in total cholesterol (-0.56aEuroS +/- aEuroS0.95 mmol/L; PaEuroS=aEuroS0.001), low-density lipoprotein cholesterol (-0.31aEuroS +/- aEuroS0.81 mmol/L; PaEuroS=aEuroS0.039) and triglycerides (-0.59aEuroS +/- aEuroS1.12aEuroSmmol/L; PaEuroS=aEuroS0.001) and an increase in total hip bone mineral density (+0.9aEuroS +/- aEuroS1.5%; PaEuroS=aEuroS0.013) In long-term-experienced patients, maraviroc/raltegravir therapy lacks virological robustness despite a benefit in lipid profile and bone density.