Researchers in France conducted an exploratory study with 44 HIV-positive participants. Their average age was 55 years and they had been taking ART for 15 years. For the five years prior to the study, their viral loads were less than 50 copies/ml.
All participants were experiencing fat gain in their bodies (lipohypertrophy). On entering the study, participants had their regimens changed to the following:
- raltegravir (sold as Isentress) 400 mg twice daily
- maraviroc (sold as Celsentri) 300 mg twice daily
The study called "Roc 'n Ral" was expected to last for 48 weeks. However, an independent panel of doctors charged with monitoring the safety of participants recommended that the study be halted prematurely. The researchers said this recommendation arose because of an "excessive rate of treatment failure."
In total, seven out of 44 enrolled participants (recruitment was supposed to have been 90 participants) experienced the following problems:
- virologic failure (viral load persisted above the 50-copy/ml log): five cases
- adverse events: one case of hepatitis B virus (HBV) reactivation. This occurred because neither raltegravir nor maraviroc have anti-HBV activity and the participant's previous regimen included the drug 3TC (lamivudine), which has activity against both HIV and HBV. There was also one case of rash and diarrhea.
A Closer Look
In two of the five cases of virologic failure, analysis of blood samples from these participants suggested that levels of raltegravir and maraviroc were very low. It is therefore likely that these two participants were not taking their medicines as directed. Furthermore, in these participants, HIV was not resistant to either drug, which is also highly suggestive that they were not taking these drugs.
In the remaining three participants, HIV became resistant to at least one of the study drugs.
All five participants with virologic failure left the study and resumed their pre-study regimen and their viral load once more fell below the 50-copy/ml mark.
There were 22 other participants whose viral loads were suppressed at the end of the study. They chose to continue taking raltegravir + maraviroc.
Assessments of blood samples found decreased levels of total cholesterol, LDL-cholesterol and triglycerides over the course of the study for most participants.
In a subset of 24 men for whom low-dose X-ray scans (called DEXA) were available both before and at the 24th week of the study, bone mineral density increased by about 1%. Had the study continued for a year, researchers suggested that this would have increased to 2%.
There were no significant changes to the distribution of body fat.
In this exploratory study, a combination of maraviroc and raltegravir was able to keep HIV suppressed in 79% of participants. Note that 100% of participants had a suppressed viral load on ART prior to entering this study.
The research team states that the combination of maraviroc and raltegravir as dual therapy "lacks virological robustness ... and therefore cannot be recommended for further evaluation in a larger scale."
Katlama C, Assoumou L, Valantin MA, et al. Maraviroc plus raltegravir failed to maintain virological suppression in HIV-infected patients with lipohypertrophy: results from the ROCnRAL ANRS 157 study. Journal of Antimicrobial Chemotherapy. 2014; in press.