NRTI-sparing
Regimen of Lopinavir/ritonavir plus Raltegravir Works as Well as Traditional
3-drug HAART
 |
 |
 |
 |
 |
 |
 |
| SUMMARY:
An antiretroviral therapy (ART) regimen consisting of the
protease inhibitor lopinavir/ritonavir
(Kaletra) plus the integrase inhibitor raltegravir
(Isentress) suppressed HIV viral load as well as a traditional
3-drug highly active ART (HAART) combination, while avoiding
potential adverse side effects of nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs), according to study findings
reported this week at the XVIII International AIDS Conference
(AIDS 2010) in Vienna. |
|
 |
 |
 |
 |
 |
 |
 |
By
Liz Highleyman
HAART
regimens to date have typically included a protease
inhibitor or non-nucleoside
reverse transcriptase inhibitor (NNRTI) plus a "backbone"
of 2 NRTIs. Development
of new drug classes -- including integrase
inhibitors that prevent HIV from inserting its genetic material
into host cells -- offers new options for constructing potent combination
regimens.
Jacques
Reynes and fellow investigators with the PROGRESS (PROtease/InteGRasE
Simplification Study [aka M10-336]) team designed this open-label Phase
3 trial to compare a traditional 3-drug HAART regimen and a 2-drug NRTI-sparing
combination.
A total
of 206 treatment-naive participants were randomly assigned (1:1) to
receive 400/100 mg twice-daily lopinavir/ritonavir
combined with either 400 mg twice-daily raltegravir
-- but no NRTIs -- or else once-daily tenofovir/emtricitabine
(Truvada).
Most participants
(about 85%) were men, 75% were white, 21% were black, and the average
age was 49 years. All had plasma viral load > 1000 copies/mL -- with
a mean of about 20,000 -- and the average CD4 count was nearly 300 cells/mm3.
The primary
endpoint of undetectable viral load (< 40 copies/mL) at 48 weeks
was reported at AIDS 2010, but follow-up is continuing through 96 weeks.
Results
 |
In
a 48-week intent-to-treat TLOVR analysis, 83.2% of participants
in the raltegravir group and 84.8% in the tenofovir/emtricitabine
group achieved undetectable viral load. |
|
This
difference of -1.6% easily fell within the predefined non-inferiority
thresholds of 20% and 12%, allowing investigators to conclude that
the NRTI-sparing combination was non-inferior to the traditional
HAART regimen. |
|
Raltegravir
suppressed viral load in more patients during the early treatment
period -- with significant differences at weeks 2, 4, 8, and 16
-- but tenofovir/emtricitabine caught up by week 24. |
|
CD4
cell counts rose by statistically similar amounts at all time points,
ending with gains of 215 cells/mm3 in the raltegravir group and
245 cells/mm3 in the tenofovir/emtricitabine group. |
|
Both
study regimens were generally well-tolerated. |
|
8%
of participants in the raltegravir arm and 11% in the tenofovir/emtricitabine
arm discontinued the study for any reason, not a significant difference. |
|
2
patients in both groups quit due to adverse events; 1 in the raltegravir
group and 2 in the tenofovir/emtricitabine group did so due to virological
failure. |
|
The
most common side effects, occurring at similar rates in the raltegravir
and tenofovir/emtricitabine arms, were diarrhea (8% vs 13%, respectively)
and elevated cholesterol (8% vs 5%, respectively). |
|
Total
cholesterol, HDL "good" cholesterol, and triglyceride
levels increased by a larger average amount, and in more patients,
in the raltegravir arm. |
|
1
person in each arm had evidence of drug resistance mutations, but
there were no new protease resistance mutations. |
Based
on these findings, the PROGRESS investigators concluded that lopinavir/ritonavir
plus raltegravir "resulted in non-inferior efficacy and similar
tolerability as a traditional 3-drug antiviral regimen."
"The
48-week PROGRESS study results, while not definitive, suggest that the
nucleoside-sparing HIV regimen of Kaletra and Isentress may be an alternative
treatment option for patients new to HIV therapy, when compared to a
standard HIV regimen." Reynes said in a press release issue by
Abbott, the maker of lopinavir/ritonavir.
Investigator
affiliations: Hôpital Gui de Chauliac, Montpellier, France; Abbott,
Abbott Park, IL; Hospital 12 de Octubre, Universidad Complutense de
Madrid, Madrid, Spain; Innovative Care PSC, Bayamon, Puerto Rico; Therapeutic
Concepts, Houston, TX.
7/23/10
Reference
J
Reynes, A Lawal, F Pulido, and others. Lopinavir/ritonavir combined
with raltegravir demonstrated similar antiviral efficacy and safety
as lopinavir/ritonavir combined with tenofovir disoproxil fumarate/emtricitabine
in treatment-naive HIV-1 infected subjects: PROGRESS 48 week results.
XVIII International AIDS Conference. Vienna, July 18-23, 2010. Abstract
MOAB0101.
Other
Source
Abbott.
Abbott's PROGRESS Study of Kaletra and Isentress Compared with a Standard
HIV Regimen Meets the Pre-Specified Primary Efficacy Endpoint. Press
release. July 19, 2010.
