Study Finds Boosted Darunavir (Prezista) Monotherapy Maintains
HIV Suppression as well as Standard Combination Antiretroviral
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.
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
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.
an intent-to-treat switch=failure analysis, analysis, 84.3%
and 85.3%, respectively, maintained undetectable viral load.
an as-treated analysis including switches, the corresponding
rates of viral suppression were 93.5% and 95.1%, respectively.
3 comparisons showed that darunavir/ritonavir monotherapy
was non-inferior to standard combination therapy.
patients in the monotherapy arm and 19 in the combination
arm experienced protocol-defined treatment failure.
a multivariate analysis, HCV coinfection -- which was more
common in the monotherapy group -- was a significant predictor
of HIV viral load blips.
load was re-suppressed when NRTIs were reintroduced
cell counts remained stable during the trial in both arms.
patient in each arm had at least 1 PI resistance mutation,
and 1 person in the combination arm had a NRTI resistance
patients in each arm discontinued their assigned treatment,
either due to adverse events or for other reasons.
new or unexpected safety signals were detected.
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
"[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."
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.
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."
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.
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):
January 16, 2010.