Viral rebound after switch to maraviroc/raltegravir dual therapy in highly experienced and virologically suppressed patients with HIV-1 infection

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

“…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 . The MVC plus RAL was effective in 10 naive patients treated for 24 weeks with an induction therapy (TDF/FTC plus RAL plus MVC) and then switched to dual therapy: after 48 weeks, undetectable viral load was maintained in all patients 20 .…”

“…In a similar way, even in dual PI-sparing, pharmacological compatibility could play a role. In 26 patients treated with MVC plus RAL and a third drug, switching to RAL plus MVC showed a high rate of failure at week 24, and 60% of patients had MVC C trough lower than minimum effective concentration for experienced patients (50 ng/ml) 19 . This is contrary to previous data on the MVC plus RAL plus ETV combination, where no excess rate of virologic failure was observed in a similar clinical setting and in the presence of comparable MVC plasma exposure 52 .…”

Complexity and Dynamics of HIV-1 Chemokine Receptor Usage in a Multidrug-Resistant Adolescent

“…However, it has to be mentioned that a rebound after a switch to RAL/MVC therapy is not surprising, as was also described in R5-infected and virologically suppressed patients. 35 The effect on patients carrying dual-tropic viruses, such as the adolescent described here, has not yet been investigated.…”