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 (δ=−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 (δ = −4.9%, 90% confidence interval, from −9.1 to −0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, δ = −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.
Conclusion: 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.
aINSERM UMR-S 943 and University Pierre and Marie Curie (UPMC) Paris VI, France
bDepartment of Infectious Diseases, Assistance Publique Hôpitaux de Paris (AP-HP) Pitié-Salpêtrière Hospital and UPMC Paris VI, France
cDepartment of Infectious Diseases, AP-HP, Necker Hospital, France
dDepartment of Virology, AP-HP, Pitié-Salpêtrière Hospital, France
eDepartment of Infectious Diseases, AP-HP, Saint Antoine Hospital, France
fDepartment of Infectious Diseases, AP-HP, Saint Louis Hospital, France
gDepartment of Infectious Diseases, Saint-Jacques Hospital, France
hLaboratory of Toxicology and Pharmacokinetic, AP-HP, Bichat-Claude Bernard Hospital, Paris, France.
Received 7 June, 2010
Revised 5 July, 2010
Accepted 5 July, 2010
Correspondence to Professor Christine Katlama, MD, Hôpital Pitié-Salpêtrière, Paris, France. Tel: +33 1 42 16 01 42; fax: +33 1 42 16 01 26; e-mail: email@example.com