MVC + DRV-r Maintains HIV Suppression in Retreated Patients

September 2, 2014

A once daily MVC plus DRV/r regimen had an effective role in antiretroviral drug-pretreated individuals with controlled HIV infection in this trial. In an aging HIV-infected population, with increasing comorbidities, this combination could be a safer option than standard triple therapy. More here.

HIV-infected patients previously exposed to antiretroviral drugs who take once-daily maraviroc (MVC) plus ritonavir-boosted darunavir (DRV-r) because of simplification or adverse effects can maintain HIV suppression in most instances in a real-life setting, according to a new study.

Nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens may be needed in patients with NRTI toxicity. MVC plus DRV-r or atazanavir is associated with slightly lower response rates than triple therapy in drug-naïve patients. But these combinations had not been tested in pretreated patients.

Researchers conducted a retrospective cohort study to assess the efficacy and safety of MVC 150 mg plus DRV/r 800/100 mg once-daily in 60 HIV-infected pretreated patients. Reasons for starting MVC plus DRV/r were adverse effects in 38 patients (63%), simplification in 15 patients (25%), and virologic failure in 7 patients (12%).

Results show that 47 patients (78%) achieved HIV RNA <50 copies/mL at 48 weeks. On-treatment analysis showed that 42 of 49 patients (86%) presented HIV RNA <50 copies/mL at 48 weeks. Median CD4 cell counts also increased at 48 weeks.

The combination was well-tolerated, and no unexpected side effects were recorded during the first 48 weeks in patients taking MVC plus DRV/r. Only 1 patient discontinued therapy because of adverse effects.

The results may contrast with those of recently reported clinical trials that recruited antiretroviral drug-naïve patients, which show lower response rates for the dual therapy arm. The researchers believe the virologic response to MVC plus DRV/r is similar to that of combinations including efavirenz.

“In the present study, there was no signal of low potency related to MVC plus DRV/r. Pretreated individuals who were selected to receive that combination, because of CCR5 tropism and lack of resistance mutations for DRV/r, did well and no significant changes in the proportion of patients with HIV suppression were observed,” they note.

Seven patients started MVC plus DRV/r because of virologic failure on a previous antiretroviral regimen. Two of these patients showed undetectable plasma HIV RNA and another 2 patients had low-level viremia at week 48. The dual combination of MVC plus DRV/r does not seem advisable as rescue therapy for failing regimens, the researchers noted.

Liver function tests and AST to platelet ratio index decreased during the first 48 weeks in patients taking MVC plus DRV/r. This effect was not attributable to switches because of liver toxicity. “The initiation of an NRTI-sparing regimen could reduce the grade of pre-existing hepatic steatosis or steatohepatitis,” the researchers state, noting that the use of either MVC or DRV/r has been shown to have a lower likelihood of hepatic steatosis. “Thus, a regimen including both might provide some additional benefit in terms of preventing fatty liver disease in these patients.”

The researchers conclude that the combination “seems to be a regimen that can be effectively used in antiretroviral drug-pretreated individuals with controlled HIV infection. The tolerability of this dual combination can prevent the accumulation of adverse events associated with NRTI-containing drug regimens. In an aging HIV-infected population, with increasing comorbidities, MVC plus DRV/r could be a safer option than standard triple therapy.”

The researchers published their results in the August 2014 issue of HIV Medicine.