Raltegravir
(Isentress), Etravirine (Intelence), and Boosted Darunavir
(Prezista) Is Effective for Heavily Treatment-experienced
Patients
Adding
new drugs one by one to a failing antiretroviral
therapy (ART) regimen can promote development of
drug resistance. But the approval of a number of new
agents over the past few years -- including some novel
drug classes -- has enabled construction of active regimens
for highly treatment-experienced patients. The introduction
of 2 or 3 fully active new drugs in people on failing
ART is a key factor in subsequent treatment efficacy.
French
Study
In
the first study, described in the November
1, 2009 issue of Clinical Infectious Diseases,
researchers with the ANRS 139 TRIO study team assessed
the safety and efficacy of a regimen containing the
integrase inhibitor raltegravir, the next-generation
non-nucleoside reverse transcriptase inhibitor (NNRTI)
etravirine, and the protease inhibitor (PI) darunavir/ritonavir
in heavily pre-treated patients.
This
Phase 2, non-comparative trial included 103 patients
at multiple centers in France who had extensive prior
antiretroviral drug use, but were naive to the 3 study
drugs. At baseline, they had plasma HIV RNA levels >1000
copies/mL, a history of virological failure while receiving
NNRTIs, at least 3 primary PI and nucleoside reverse
transcriptase inhibitor (NRTI) resistance mutations,
and 3 or fewer darunavir and NNRTI resistance mutations.
Baseline genotypic resistance profiles showed a median
of 4 primary PI mutations, 1 NNRTI mutation, and 6 NRTI
mutations.
In
addition to raltegravir, etravirine, and darunavir/ritonavir,
most (87%) also received optimized background therapy
that included NRTIs (86 patients) and/or enfuvirtide
(T-20; Fuzeon) (12 patients).
Results
 |
At
week 4, 55% of the treated patients had undetectable
viral load. |
|
By
week 12, this proportion had increased to 88%. |
|
At
week 24, 90% of patients had HIV RNA < 50 copies/mL.
|
|
At
week 48, 86% reached this viral load level. |
|
The
median CD4 cell count increase was 108 cells/mm3.
|
|
15%
of patients reported grade 3 or 4 clinical adverse
events. |
|
19%
experienced moderate-to-severe laboratory abnormalities. |
|
Only
1 patient, however, discontinued the investigational
regimen due to an adverse event. |
Based
on these findings, the researchers concluded, "In
patients infected with multidrug-resistant virus who
have few remaining treatment options, the combination
of raltegravir, etravirine, and darunavir/ritonavir
is well tolerated and is associated with a rate of virologic
suppression similar to that expected in treatment-naive
patients."
Hôpital
Tourcoing, Lille School of Medicine, Lille; INSERM U897,
Bordeaux; Hôpital Bichat?Claude Bernard, Paris;
Hôpital Bicetre, Le Kremlin Bicetre, Paris; Hôpital
Pitie?Salpetriere, Paris; Hôpital Tenon, Paris;
Hôpital Georges Pompidou, Paris; Hôpital
Saint Antoine, Paris; Hôpital Saint Louis, Paris;
Université de Paris Diderot, Paris; Hôpital
Clermont?Ferrand, Clermont?Ferrand, France.
Spanish
Study
In
the second study, reported in the November
2009 Journal of Acquired Immune Deficiency Syndromes,
Spanish researchers evaluated 32 consecutive heavily
treated-experienced patients with multidrug-resistant
HIV who started a new salvage regimen containing raltegravir
(400 mg twice-daily), etravirine (200 mg twice-daily),
and darunavir/ritonavir (600/100 mg twice-daily.
Participants
had been on ART for a median of 13 years. The median
baseline CD4 count was 261 CD4 cells/mm3. Within this
group, 16 patients (50%) had taken enfuvirtide and 14
(44%) had taken tipranavir (Aptivus). All had HIV with
resistance to 3 drug classes, and 3 (9%) had virus with
3 etravirine resistance mutations. All were darunavir-naive,
with a median of 1 darunavir resistance mutation.
Results
|
At
Week 4, 63% of participants had HIV RNA < 50
copies/mL. |
|
At
Week 12, this figure reached 81%. |
|
By
Week 24, 94% had undetectable viral load. |
|
Median
CD4 cell count increased by 30, 73, and 103 cells/mm3
at Weeks 4, 12, and 24, respectively. |
|
No
patients experienced adverse events leading to discontinuation
of the study regimen. |
As
with the French team, the Spanish researchers concluded
that, "The combination of raltegravir, etravirine,
and darunavir/ritonavir was a highly effective and well-tolerated
antiretroviral salvage regimen in patients infected
with multidrug-resistant HIV-1."
Infectious
Diseases Department, Hospital Universitari Vall d'Hebron
and Departament de Medicina, Universidad Autónoma
de Barcelona, Barcelona, Spain; Infectious Disease Unit,
Hospital Universitari Son Dureta, Palma de Mallorca,
Spain; Microbiology Department, Hospital Universitari
Vall d'Hebron, Universidad Autónoma de Barcelona,
Barcelona, Spain; Microbiology Department, Hospital
Universitari Son Dureta, Palma de Mallorca, Spain.
10/30/09
References
Y
Yazdanpanah, C Fagard, D Descamps, and others.
High rate of virologic suppression with raltegravir
plus etravirine and darunavir/ritonavir among treatment-experienced
patients infected with multidrug-resistant HIV: results
of the ANRS 139 TRIO trial. Clinical Infectious Diseases
49(9):1441-1449. November 1, 2009. (Abstract).
A
Imaz, SV del Saz, MA Ribas, and others. Raltegravir,
Etravirine, and Ritonavir-Boosted Darunavir: A Safe
and Successful Rescue Regimen for Multidrug-Resistant
HIV-1 Infection. Journal of Acquired Immune Deficiency
Syndromes 52(3): 382-386. November 2009. (Abstract).
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