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and Hepatitis.com Coverage of the
XVIII International AIDS Conference (AIDS 2010) July 18 - 23, 2010, Vienna, Austria
Boosted Darunavir (Prezista) Monotherapy Provides Durable Viral Suppression for Most HIV Patients
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.
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%.
"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.