Boosted Darunavir (Prezista) Monotherapy Provides Durable Viral Suppression for Most HIV Patients

		SUMMARY: More than 90% of patients who switched from a suppressive combination antiretroviral therapy (ART) regimen to ritonavir-boosted darunavir (Prezista) without nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) had undetectable viral load at 96 weeks, according to long-term data from the MONET study presented at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. Taking into account participants who experienced 2 viral "blips" or made a change from their randomized regimen, however, darunavir/ritonavir monotherapy was not quite as effective as 3-drug combination therapy.

By Liz Highleyman

Prezista (darunavir) • News Articles • Full US Prescribing Information

Standard highly active antiretroviral therapy, or HAART, consists of a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a "backbone" of 2 NRTIs. Newer protease inhibitors are highly potent, leading researchers to test whether using them alone, boosted with ritonavir, might be an equally effective but more convenient treatment option without NRTI-related drug toxicities.

The MONET study enrolled 256 patients in Europe who were taking a standard 3-drug regimen and had maintained viral suppression < 50 copies/mL for at least 6 months. Participants were randomly assigned (1:1) to switch to 800/100 mg once-daily darunavir/ritonavir, either alone or in combination with 2 NRTIs.

Most participants (about 80%) were men, about 90% were white, and the median age was 44 years. Patients had been on ART for an average of 6-7 years and had a median CD4 cell count of 575 cells/mm3; 57% switched from PI-based combination regimens while 43% switched from NNRTI-based regimens. About twice as many people in the monotherapy arm had hepatitis C virus (HCV) coinfection (9% vs 16%).

Data from a 48-week analysis were published in the January 16, 2010 issue of AIDS. Briefly, in a time to loss of virological response (TLOVR) analysis -- with treatment failure defined as 2 consecutive HIV RNA measurements > 50 copies/mL or discontinuation of assigned regimen -- 86.2% of participants in the darunavir/ritonavir monotherapy arm and 87.8% in the combination therapy arm maintained viral load < 50 copies/mL. In an as-treated analysis including people who changed their assigned regimen, the corresponding viral suppression rates were 93.5% and 95.1%, respectively. Both comparisons showed darunavir/ritonavir monotherapy to be non-inferior to standard combination therapy.

Armin Rieger from the University of Vienna presented 96-week MONET results at AIDS 2010. Again, the primary efficacy analysis was a TLOVR analysis with treatment failure defined as 2 viral loads > 50 copies/mL or changing from the randomly assigned regimen (e.g., by re-adding NRTIs in the monotherapy arm). The secondary analysis included patients who had HIV RNA < 50 copies/mL at 96 weeks, even if they had transient detectable viral load -- or "blips" -- in the interim, and treatment changes were permitted. The margin for declaring non-inferiority was set at -12%.

Results

	In the primary TLOVR switch=failure analysis, 74.8% of patients in the darunavir/ritonavir monotherapy arm had viral load < 50 copies/mL at 96 weeks, compared with 80.6% in the 3-drug arm.
	The difference was 5.8% in favor of the 3-drug arm, but the upper end of the confidence interval (-16 to +4.4) did not fall within the 12% margin, so monotherapy could not be considered non-inferior.
	In the secondary analysis including people who changed their randomized regimen, 92.1% vs 90.7%, respectively, maintained viral suppression at 96 weeks.
	In this analysis, the difference was 1.4 in favor of monotherapy and the upper bound of the confidence interval (-5.5 to +8.3) fell within the 12% margin, allowing the researchers to conclude that monotherapy was non-inferior.
	In a univariate analysis, hepatitis C coinfection and history of injection drug use were significant predictors of treatment failure in the TLOVR analysis, though only hepatitis C remained significant in a multivariate analysis adjusting for other factors.
	1 patient in each arm showed genotypic evidence of a major protease inhibitor resistance mutation, but both had HIV RNA < 50 copies/mL at week 96.
	All but 1 patient (88%) in the monotherapy arm who re-intensified therapy by adding back NRTIs achieved re-suppression to < 50 copies/mL.
	The rate of serious adverse events was the same in both arms (10%).

"In the primary efficacy analysis at Week 96, rates of double HIV RNA blips and discontinuations were slightly higher in the darunavir/ritonavir monotherapy arm, compared with the darunavir/ritonavir + 2NRTI arm," the MONET investigators concluded. "Non-inferiority was shown in the 'Switch Included' analysis."

"Most elevations in HIV RNA were low level (50-200 copies/mL), and patients were re-suppressed < 50 copies/mL at Week 96, either on the original randomized treatment or with intensified treatment," they added.

Investigator affiliations: General Hospital, University of Vienna, Vienna, Austria; Belgyogyaszati Osztaly, Budapest, Hungary; Medizinisches Versorgungszentrum, Berlin, Germany; Liverpool University, Pharmacology, London, United Kingdom; Hospital la Paz, Madrid, Spain; Janssen-Cilag, Medical, Tilburg, Netherlands; Janssen-Cilag, Neuss, Germany.

8/17/10

Reference
A Rieger, D Banhegyi, W Schmidt, and others. The MONET trial 96 week analysis: darunavir/ritonavir monotherapy versus DRV/r + 2NRTIs, for patients with HIV RNA < 50 copies/mL at baseline. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract THLBB209.

Launch Talking Slides™