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.
BACKGROUND
The introduction of 2 or 3 fully active drugs in human immunodeficiency virus (HIV)-infected patients receiving failing antiretroviral therapy is a key determinant of subsequent treatment efficacy. The aim of this study was to assess the safety and efficacy of a regimen containing raltegravir, etravirine, and darunavir/ritonavir for treatment-experienced patients infected with multidrug-resistant HIV.


METHODS
Patients enrolled in this phase II, noncomparative, multicenter trial were naive to the investigational drugs and had plasma HIV RNA levels >1000 copies/mL, a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors (NNRTI), > or =3 primary protease inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) mutations, and < or =3 darunavir and NNRTI mutations. The primary end point was the proportion of patients with plasma HIV RNA levels <50 copies/mL at 24 weeks.


RESULTS
A total of 103 patients enrolled in the study. At baseline, genotypic resistance profiles showed a median of 4 primary protease inhibitor mutations, 1 NNRTI mutation, and 6 NRTI mutations. In addition to the investigational drugs, 90 patients (87%) received optimized background therapy that included NRTIs (86 patients) or enfuvirtide (12 patients). At week 24, 90% of patients (95% confidence interval, 85%-96%) had an HIV RNA level <50 copies/mL. At week 48, 86% (95% confidence interval, 80%-93%) had an HIV RNA level <50 copies/mL. The median CD4 cell count increase was 108 cells/mm(3). Grade 3 or 4 clinical adverse events were reported in 15 patients (14.6%). Only 1 patient discontinued the investigational antiretroviral regimen, because of an adverse event.


CONCLUSIONS
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.
Yazdanpanah
Y
Y
Hôpital Tourcoing, Lille School of Medicine, Lille, France. yyazdan@yahoo.com
Fagard
C
C
Descamps
D
D
Taburet
A M
AM
Colin
C
C
Roquebert
B
B
Katlama
C
C
Pialoux
G
G
Jacomet
C
C
Piketty
C
C
Bollens
D
D
Molina
J M
JM
Chêne
G
G
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir