Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136.
BACKGROUND
Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs.


METHODS
MONOtherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the monotherapy arm (delta =-10%, 90% confidence interval).


RESULTS
A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events.


CONCLUSIONS
Darunavir/r monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
Katlama
Christine
C
INSERM UMR-S 943 and University Pierre and Marie Curie (UPMC) Paris VI, Paris, France. christine.katlama@psl.aphp.fr
Valantin
Marc A
MA
Algarte-Genin
Michele
M
Duvivier
Claudine
C
Lambert-Niclot
Sidonie
S
Girard
Pierre M
PM
Molina
Jean M
JM
Hoen
Bruno
B
Pakianather
Sophie
S
Peytavin
Gilles
G
Marcelin
Anne G
AG
Flandre
Philippe
P
D000328:Adult; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005602:France / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir