Nucleoside
reverse transcriptase inhibitors (NRTIs) can cause long-term side effects such
as lipoatrophy and mitochondrial toxicity, and researchers have therefore explored
NRTI-sparing regimens that omit the standard HAART "backbone" of 2 drugs
from this class.
Data
from 2 trials assessing this strategy were presented at the 8th Annual International
Congress on Drug Therapy in HIV Infection (HIV8), held last week in Glasgow.
In
the first study, researchers assessed the efficacy and tolerability of a regimen
containing 2 protease inhibitors -- lopinavir/ritonavir (Kaletra) and atazanavir
(Reyataz) -- without a nucleoside backbone.
Subjects
with viral loads below 50 copies/mL were eligible for this 48-week prospective
pilot sub-study upon completion of the main pharmacokinetic (PK) study looking
at co-administration of the 2 drugs. During the PK study, subjects took lopinavir/ritonavir
400/100 mg twice daily plus atazanavir 300 mg once daily plus NRTIs.
Four
subjects then decided to enter the sub-study and discontinued their NRTIs. Efficacy
and safety were assessed at 7 visits over 48 weeks.
Results
•
All 4 subjects in the
sub-study completed 48 weeks on lopinavir/ritonavir plus atazanavir.
•
At Week 48, all 4 maintained
virological suppression (HIV RNA < 50 copies/mL).
•
Mean CD4 cell count
rose from 569 cells/mm3 (range 344-929) at baseline to 663 cells/mm3 (range 390-911)
at Week 48.
•
One subject experienced
a Grade 1 increase in plasma bilirubin concentration.
•
No other adverse events
were observed, and no subjects experienced Grade 3/4 events.
Lopinavir/ritonavir
plus atazanavir "was shown to be efficacious and well tolerated," the
researchers concluded. "There were no virologic failures and the mean CD4
T-cells increased."
"Although
the study population was small, these results suggest that this dual PI combination
is a safe and effective nucleoside sparing regimen," they added, and "further
studies are warranted."
NEVATA
Study
The
second study looked at a NRTI-sparing regimen consisting of boosted atazanavir
plus nevirapine (Viramune). The NEVATA pilot study included 59 treatment-experienced
patients with durable viral suppression who were randomly assigned to either receive
atazanavir/ritonavir 300/100 mg plus nevirapine 200 mg twice daily (n = 30) or
to continue triple therapy consisting of lopinavir/ritonavir 400/100 mg twice
daily plus 2 NRTIs (n = 29). Baseline characteristics were similar in the 2 arms.
Results
•
Week 24 data from 28
patients in each group were presented.
•
Similar proportions
of patients in both arms had undetectable viral load (89% in the atazanavir/ritonavir
+ nevirapine arm and 82% in the triple-therapy arm with HIV RNA < 400 copies/mL;
11% in each arm < 40 copies/mL).
•
There were no significant
differences in median CD4 cell count (450 vs 510 cells/mm3).
•
The atazanavir/ritonavir
+ nevirapine arm experienced an increase in total cholesterol (522 to 578 mmol/L),
but the difference was non-significant compared with the triple therapy group.
•
Median HDL ("good")
cholesterol was higher the atazanavir/ritonavir + nevirapine arm (155 vs 117 mmol/L;
P < 0.0001).
•
Triglyceride levels
decreased in the atazanavir/ritonavir + nevirapine arm (224 vs 156 mmol/L; P <
0.0001).
Dual
therapy with atazanavir/ritonavir plus nevirapine is [as] potent and safe as standard-of-care
HAART at Week 24 of follow-up," the researchers concluded. "These preliminary
data suggest a significant improvement in triglyceride profile and in HDL-cholesterol
level in the nucleoside-sparing regimen."
11/21/06
References
D
A Parks, H C Jennings, C W Taylor, and others. Efficacy and safety of lopinavir/r
and atazanavir without a nucleoside backbone in antiretroviral therapy experienced
HIV-infected subjects. 8th Annual International Congress on Drug Therapy in HIV
Infection (HIV8). Glasgow, UK. November 12-16, 2006. Abstract P42.
A M
Cattelan, M Trevenzoli, S Cavinato, and others. Atazanavir/ritonavir in combination
with nevirapine as a nucleoside-sparing strategy in HIV-infected antiretroviral-experienced
subjects (NEVATA study). HIV8. Abstract 38.
