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

Abstract

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 (-0.56 ± 0.95 mmol/L; P = 0.001), low-density lipoprotein cholesterol (-0.31 ± 0.81 mmol/L; P = 0.039) and triglycerides (-0.59 ± 1.12 mmol/L; P = 0.001) and an increase in total hip bone mineral density (+0.9 ± 1.5%; P = 0.013) CONCLUSIONS: In long-term-experienced patients, maraviroc/raltegravir therapy lacks virological robustness despite a benefit in lipid profile and bone density.

Pharmacokinetic and pharmacodynamic evaluation of raltegravir and experience from clinical trials in HIV-positive patients

“…Beside these studies using three-drug regimens, several small observational or interventional studies described the effects of substituting NRTIs backbone with raltegravir (dual PI-based HAARTs) or of switching triple regimens to dual therapies: the latter include the combination of raltegravir with atazanavir, atazanavir/ritonavir, etravirine, nevirapine and maraviroc [56][57][58][59][60][61][62]. The results are somehow heterogeneous but they globally indicate a good tolerability of such regimens and a limited barrier to resistance with resistance-associated mutation often selected at failure.…”

“…The results are somehow heterogeneous but they globally indicate a good tolerability of such regimens and a limited barrier to resistance with resistance-associated mutation often selected at failure. Specifically, two studies highlighted that raltegravir plus maraviroc in patients with controlled plasma viremia was insufficient to maintain short-term viral suppression [61,62].…”

State of the Art of Dual Therapy in 2015

“…It is important to highlight that patients received NRTI-sparing regimens without ritonavir in these two studies 47 . In the KITE study, the switch to RAL plus LPV/r was associated with increases in fasting plasma total chol esterol, triglycerides, and LDL-cholesterol levels at 24 weeks, but only the increase in triglyceride levels was statistically significant 18 .…”

“…The ROCnRAL trial 18 is a single-arm study that switched 44 patients from a suppressive HAART to MVC 300 mg twice daily plus RAL 400 mg twice daily with R5 tropic virus and undetectable viral load from 5.2 years (IQR: 4.4-7.9), nadir CD4 210 cells/mm 3 (IQR: 150-276), HAART duration 15 years (IQR: 15-19); seven (16%) patients failed MVC/RAL therapy: five with virological failure and two discontinued treatment due to adverse events. The high rate of virologic failure of this dual combination was confirmed by an Italian study: 9/26 (35%) multi-experienced patients failed simplification therapy with MVC plus RAL at week 24 19 .…”

“…In two different studies of switching to dual therapy based on RAL plus entecavir (ETV), the authors registered a decrease in median cholesterol, triglyceride levels, and glucose levels 21,22 . The French study ROCnRAL was based on the switch to dual therapy with RAL plus MVC in patients with lipo dystrophy: lipid profiles improved with a decrease from baseline values in total cholesterol, but two patients discontinued treatment due to severe adverse events (HBV rebound in a patient HBcAb + and HBsAg -, one hypersensitivity syndrome) 18 . Due to the limited number of patients and the observational and nonrandomized nature of the study, all these data should be carefully considered.…”