MONET Study Finds Boosted Darunavir (Prezista) Monotherapy Maintains HIV Suppression as well as Standard Combination Antiretroviral Therapy

		SUMMARY: Patients with undetectable viral load who switched from standard antiretroviral therapy (ART) regimens to ritonavir-boosted darunavir (Prezista) monotherapy maintained HIV RNA suppression and stable CD4 cell counts, according to findings from the MONET study reported in the January 16, 2010 issue of AIDS. Investigators concluded that darunavir/ritonavir monotherapy is non-inferior to triple therapy in this carefully selected population.

By Liz Highleyman

While combination antiretroviral therapy has proven highly successful, researchers have explored simplified regimens that potentially could increase convenience and adherence while decreasing side effects and costs.

One such strategy is protease inhibitor (PI) monotherapy (the small boosting dose of ritonavir is not counted as a separate drug). Prior studies indicated that starting treatment with a single boosted PI (usually lopinavir/ritonavir [Kaletra]) is inferior to starting with a standard combination regimen such as a PI plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). But monotherapy may be adequate for maintaining viral suppression in people simplifying from a combination regimen.

The European MONET study included 256 HIV patients taking a standard 3-drug regimen who had achieved and maintained a viral load below 50 copies/mL for at least 6 months (57% on PI-base regimens, 43% on NNRTI-based regimens). Participants were randomly assigned to switch to 800/100 mg once-daily darunavir/ritonavir, either alone or in combination with 2 NRTIs.

Most participants were men (81%), 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 well-controlled HIV disease, with a median CD4 cell count of 574 cells/mm3. About twice as many patients in the monotherapy arm had hepatitis C virus (HCV) coinfection (17% vs 9%).

Treatment failure was defined as 2 consecutive HIV RNA measurements above 50 copies/mL by week 48 or switching from the assigned study regimen.

Results

	In a 48-week TLOVR (time to loss of virological response) analysis, 86.2% of participants in the darunavir/ritonavir monotherapy arm maintained a viral load below 50 copies/mL, compared with 87.8% in the combination therapy arm.
	In an intent-to-treat switch=failure analysis, analysis, 84.3% and 85.3%, respectively, maintained undetectable viral load.
	In an as-treated analysis including switches, the corresponding rates of viral suppression were 93.5% and 95.1%, respectively.
	All 3 comparisons showed that darunavir/ritonavir monotherapy was non-inferior to standard combination therapy.
	20 patients in the monotherapy arm and 19 in the combination arm experienced protocol-defined treatment failure.
	In a multivariate analysis, HCV coinfection -- which was more common in the monotherapy group -- was a significant predictor of HIV viral load blips.
	Viral load was re-suppressed when NRTIs were reintroduced
	CD4 cell counts remained stable during the trial in both arms.
	1 patient in each arm had at least 1 PI resistance mutation, and 1 person in the combination arm had a NRTI resistance mutation.
	9 patients in each arm discontinued their assigned treatment, either due to adverse events or for other reasons.
	No new or unexpected safety signals were detected.

Based on these findings, the MONET investigators ocncluded, "In this study for patients with HIV RNA less than 50 copies/mL on other antiretrovirals at baseline, switching to darunavir/ritonavir monotherapy showed non-inferior efficacy versus triple antiretroviral therapy."

"[A]lthough this strategy warrants further evaluation," they added in their discussion, "these data suggest that a switch to darunavir/ritonavir monotherapy can be considered in treatment-experienced patients who have a history of HIV RNA levels below 50 copies/mL on other treatments, but who are wishing to avoid toxicities related to nucleoside analogues, non-nucleosides or other antiretrovirals."

When researchers presented findings from MONET and the similar MONOI study at the 2009 International AIDS Society meeting in Cape Town, some participants raised concerns about a small number of MONOI participants who experienced brain-related adverse events.

"There is a concern that the penetration of protease inhibitors into the CNS may not be sufficient to prevent replication of HIV in this compartment," the MONET authors wrote. "However, clinical data to support this concern are lacking, and darunavir does show levels in the CNS above the EC50. In the MONET trial, the incidence of neurologic or psychiatric adverse events was the same in the monotherapy and triple therapy arms, but longer-term follow-up is needed to confirm these results."

Hospital la Paz, Madrid, Spain; Warsaw Hospital, Warsaw, Poland; Rigshospitalet, Copenhagen, Denmark; Universitat Köln, Germany; Chelsea and Westminster Hospital, London, UK; CHU Saint-Pierre/Maladies Infectieuses, Brussels, Belgium; Hopital 12 de Octubre, Madrid, Spain; Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK; Janssen-Cilag EMEA, Tilburg, Netherlands; Janssen-Cilag EMEA, Neuss, Germany.

1/19/10

Reference
JR Arribas, A Horban, J Gerstoft, and others. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS 24(2): 223-230 (Abstract). January 16, 2010.