Maraviroc matches boosted protease inhibitor treatment over 96 weeks

Treatment with maraviroc (Celsentri/Selzentry) is associated with durable HIV suppression and a favourable lipid profile, investigators report in HIV Medicine. The 96-week randomised study compared the safety and efficacy of antiretroviral regimens based on maraviroc to those containing a ritonavir-boosted protease inhibitor. Two years after randomisation, 90% of people in both treatment arms had an undetectable viral load and increases in CD4 cell count were also comparable. People treated with maraviroc had significant reductions in total cholesterol and triglycerides.

“Suppression of plasma viraemia to below the level of quantification, i.e. < 50 copies/ml, the current threshold for most guidelines in high-income settings, was similar between the arms, demonstrating the durability of the virological response to MVC [maraviroc] over 96 weeks,” write the authors. “Importantly, switching to MVC was associated with significant lipid benefits that might be important in the long term reduction in cardiovascular risk.”

Maraviroc belongs to a class of antiretrovirals known as CCR5 inhibitors. It only works for people with R5-tropic virus and individuals must be tested for its presence before initiating therapy with the drug. Forty-eight week data from the international MARCH study demonstrated that maraviroc was a safe and effective replacement for a ritonavir-boosted protease inhibitor when used in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs) in people with R5-tropic virus.

In the present study, investigators extended their analysis to 96 weeks.

The primary end-point was the proportion of people with a viral load below 50 copies/ml. Non-inferiority of maraviroc was defined as a difference of 1-2% to the boosted protease inhibitor. Secondary outcomes were changes in CD4 cell count, kidney function, lipid profile and also quality of life, adherence and adverse events.

To be eligible for recruitment, individuals were required to be taking a stable boosted protease inhibitor-based regimen and to have been virally suppressed for a least 24 weeks. Recruitment to the study took place between January 2012 and February 2014. The last person completed 96-weeks of follow-up in January 2016.

The study population consisted of 238 individuals – 82 randomised to the boosted protease inhibitor group and 156 to the maraviroc treatment arm.

The intent-to-treat analysis, including all randomised individuals, showed that 89% of the boosted protease inhibitor group and 90.4% of the maraviroc group had a viral load below 50 copies/ml at week 96, showing the non-inferiority of maraviroc.

Similar proportions of people – 13% and 17% in the boosted protease inhibitor and maraviroc groups, respectively – changed therapy during follow-up.

Adherence was measured by seven-day patient recall and was equally high in both treatment groups at week 96, with 91% of people in the boosted protease inhibitor group and 93% of people in the maraviroc arm reporting taking all their doses.

“While there has been a drive for once-daily dosing of antiretroviral therapy, the twice-daily dosing of MVC did not appear to be associated with an adherence cost,” observe the investigators.

Increases in CD4 cell count were comparable for the two groups, with an average gain at week 96 of 40 cells/mm³.

Kidney function – measured by glomerular filtration rate – declined by 4.31 ml/min and 6.53 m/min in the boosted protease inhibitor and maraviroc groups, respectively, a non-significant difference.

There was no difference in quality of life between the regimens.

Therapy with maraviroc was associated with a significantly better lipid profile over 96 weeks compared to a boosted protease inhibitor in terms of total cholesterol (p = 0.0229) and triglycerides (p < 0.001).

At least one adverse event was reported by 87% of people taking maraviroc and 79% of people taking a boosted protease inhibitor. The majority of these were mild and approximately 90% for each treatment group were not related to the study drug.

Resistant virus was detected in five people at the end of follow-up, three of whom were taking maraviroc.

The investigators conclude that the results show that switching from a boosted protease inhibitor to maraviroc is associated with “durable virological suppression, favourable metabolic changes and good tolerability over 96 weeks.”