In
an effort to simplify therapy and avoid long-term toxicities associated with nucleoside/nucleotide
reverse transcriptase inhibitors (NRTIs), researchers have explored various less
intensive regimens, including monotherapy using a single boosted protease inhibitor
(PI).
Two research
teams reported on monotherapy using lopinavir/ritonavir (Kaletra) at the 8th Annual
International Congress on Drug Therapy in HIV Infection (HIV8), held last week
in Glasgow.
IMANI
Trials
Joseph
Gathe, MD, from Therapeutic Concepts in Houston, TX -- one of the first to explore
the PI monotherapy strategy -- presented long-term follow-up data gathered for
up to 4 years.
The
IMANI I trial included 30 antiretroviral-naive patients who started single-agent
therapy with lopinavir/ritonavir. As previously reported at the 2004 International
AIDS Conference in Bangkok, 10 subjects discontinued therapy by Week 48, mostly
for reasons unrelated to treatment. The 20 patients who remained on therapy all
had viral loads below 400 copies/mL by Week 48, and 90% had viral loads below
50 copies/mL. Including all subjects who started monotherapy, the intent-to-treat
response rates were 67% and 60%, respectively.
Results
•
Of the 20 patients on monotherapy at Week 48, 18 remained on single-agent therapy,
while 2 intensified therapy by adding tenofovir/3TC [Viread/Epivir].
•
The 2 intensified patients
had viral loads below 50 copies/mL at the most recent follow-up (168 and 194 weeks).
•
15 of the 18 patients
continuing monotherapy are in active follow-up (range 152-216 weeks).
•
14 of these 15 had
viral loads below 50 copies/mL at the last measurement.
•
Episodic "blips"
(transient viral load increases) were observed in 7 patients, but were not sustained
and not associated with resistance.
•
3 patients who were
lost to follow-up (at 56, 104, and 104 weeks) had undetectable viral load at their
last measurement.
•
One patient with a
viral load of 23,460 copies/mL was described as "0% adherent" at the
last time point due to lack of access to lopinavir/ritonavir.
•
Continued CD4 cell
count improvement was seen in all patients.
•
No significant toxicity
or resistance was observed.
•
Fasting cholesterol
values were not routinely available, but no subjects were taking lipid-lowering
medications.
•
Virological success
was not compromised by switching to the new formulation lopinavir/ritonavir tablets.
Conclusion
The
researchers concluded that this follow-up data from the longest-followed cohort
of antiretroviral-naive patients on single-agent therapy revealed that 17 of 18
subjects on lopinavir/ritonavir monotherapy had undetectable viral load at the
last evaluable time point, with no evidence of genotypic or phenotypic resistance;
further, the single virological failure was due to lack of adherence
"These
promising long-term results strongly support larger stud[ies] of lopinavir/ritonavir
as an option to triple therapy HAART in antiretroviral-naive patients," they
wrote.
Dr. Gathe
and colleagues also presented data from IMANI II, an ongoing single-arm, open-label
study of lopinavir/ritonavir monotherapy in 40 antiretroviral-naive patients,
30 of whom were enrolled in a tolerability sub-study. After an average of 24 weeks
on therapy, patients switched to the new tablet formulation of lopinavir/ritonavir,
which replaced the old soft-gel capsule that included an ingredient (oleic acid)
associated with diarrhea.
A
Week 24 intent-to-treat analysis showed that 93% patients had viral loads below
400 copies/mL, and there were no cases of virological rebound following the switch.
Questionnaires completed before and 4 weeks after the switch revealed that patients
found it easier to take the new tablet. About half (14 of 30; 46.7%) reported
increased tolerability, and most (24 of 30; 80%) said they preferred the tablets.
While one-third reported moderate diarrhea with the old capsule, none did so after
switching to the tablet.
MONARK
Trial
MONARK
is an ongoing 96-week prospective, open label, pilot trial in Europe, in which
antiretroviral-naive patients were randomly assigned to receive either lopinavir/ritonavir
monotherapy (n = 83) or standard triple therapy using lopinavir/ritonavir plus
ATZ/3TC (Combivir) (n = 53).
As
previously reported, after 48 weeks of treatment, virological efficacy was similar
in both groups, although those in the monotherapy arm had more episodes of low-level
viremia.
In
Glasgow, researchers presented data on reported side effects and overall health
perception after 48 weeks of lopinavir/ritonavir monotherapy. The trial included
assessments of patient-reported side effects using a list of 22 symptoms known
to occur during HAART, as well as evaluation of patients' global health perception
(one question derived from the WHOQOL-HIV BREF scale). Questionnaires were completed
at baseline and at Weeks 4, 12, 24, and 48.
Results
•
At Week 48, the mean
total reported number of symptoms and number of symptoms causing discomfort were
significantly higher in the triple therapy arm compared with the monotherapy arm
(relative risk 1.3 and 1.4, respectively; P = 0.001 and 0.0003).
•
The proportion of
patients with a positive perception of their global health status increased in
the monotherapy arm from 32% at baseline to 68% at Week 48 (P < 0.0001), and
in the triple therapy arm from 46% to 59% (P = 0.38).
Intent-to-Treat
Comparison of Reported Symptoms
BL
= baseline, LPV/r = lopinavir/ritonavir; * P < 0.05; ** P < 0.01
Conclusion
In
conclusion, the researchers wrote, "Patients' quality of life, estimated
by the number of self-reported side effects and perception of global health, was
better with lopinavir/ritonavir monotherapy when compared with a triple regimen
of lopinavir/ritonavir plus AZT/3TC. Further exploration of lopinavir/ritonavir
monotherapy is warranted."
11/21/06
References
J
C Gathe, C Mayberry, B Miguel, and others. Long-term follow-up of IMANI I: pilot
study of the safety and efficacy of lopinavir/ritonavir (LPV/r) as single agent
therapy (SAT) in HIV-1 antiretroviral (ARV)-naive patients. 8th Annual International
Congress on Drug Therapy in HIV Infection (HIV8). Glasgow, UK. November 12-16,
2006. Abstract P5.
J
C Gathe, B Lipman, B Miguel, and others. Tolerability and preference of lopinavir/ritonavir
(Kaletra) capsules versus tablets as single agent therapy (IMANI-2). HIV8. Abstract
P62.
B Spire, F Marcellin, I Cohen Codar, and others. Impact of a lopinavir/ritonavir
(LPV/r) monotherapy on self-reported side effects and global health perception
among antiretroviral-naive patients: 48-week analysis of the MONARK Trial. HIV8.
Abstract PL13.3.
