Darunavir/r monotherapy studies
5 October 2009. Related: Conference reports, Antiretrovirals, IAS 5th Cape Town 2009.
Simon Collins, HIV i-Base
Several studies presented results from using darunavir/r monotherapy.
Jos Arribas and colleagues from the Tibotec sponsored MONET study. This study randomised 256 patients, who had been suppressed on their current HAART (< 50 copies/mL) for at least six months, to switch to darunavir/r 800/100 mg once-daily, either as monotherapy (n=127) or with 2 nukes (n=129). 
The primary endpoint was virological suppression at week 48 by TLOVR analysis (time to loss of virologic response) and the study had 80% power to show non-inferiority for the monotherapy arm (lower limit -12%).
Participants generally had responded well to their initial treatments (median CD4 ~570 cells/mm3 with only 12-14% with CD4 counts below 350 cells/mm3. Mean (+SD) prior ARV use was 6.4 (4.0) and 7.4 (4.2) years in the triple and mono arms respectively, with 48% and 35% still on their first NRTI combination. About a quarter of each group were PI-naive at baseline. A lower percentage of patients in the triple therapy arm were coinfected with HCV (11% vs 19%).
At week 48, both the per protocol and ITT analyses by TLOVR <50 copies/mL showed non-inferiority for the monotherapy arm, with 87.8% vs 86.2% (-1.6%; lower limit 95%CI: -10.1%) and 85.3% vs 84.3% (-1%; lower limit 95%CI: -9.9%), in the triple vs mono arms respectively.
CD4 remained stable at baseline levels and tolerability was good and generally similar between the two groups.
As with monotherapy studies using lopinavir/r, patients using darunavir/r monotherapy experienced more blips (n=1 vs 7) but were similarly resuppressed when nukes were added, and PI mutations were rare (in only one patient). Two patients in each arm had viral load rebounding consistently to >400 copies/mL. Nine patients per arm discontinued randomised treatment for either adverse events or other reasons. No new or unexpected safety signals were detected.
A similar study design was used for the French MONOI study, presented by Cristine Katlama as a late-breaker. 
In this study, 242 patients on HAART who were suppressed to < 400 copies/mL for at least 18 months were, after an 8-week induction phase of darunavir/r (600/100 mg bid), randomised to either continuing the triple-drug regimen (2NRTI+DRV/r) or switching to DRV/r monotherapy. Virologic failure was defined as two consecutive viral load results above 400 copies/mL, or modification/discontinuation of study treatment by week 48. The trial had 80% power to show non-inferiority for the DRV/r arm (lower limit = -10%).
Virological responses at week 48 in the Per Protocol and ITT analysis were 99.0% vs 94.2% (difference -4.9% [- 9.0 to – 0.7%]; and 92.0% vs 87.5% (difference -4.5% [-11.2 to 2.1%], for the triple and monotherapy arms respectively.
Therefore, in this study, non-inferiority was only proven for darunavir/r monotherapy in the per protocol and not the ITT analysis (although the lower margin was -10% compared to the commonly used -12%).
Even with promising results using either lopinaivr/r or darunavir/r monotherapy, there is limited data on some aspects of this strategy, including the importance of penetration into the CNS and other compartments. For patients in the UK, many of these questions will be answered by the currently-enrolling MRC-sponsored PIVOT study. 
This MRC study randomises people stable on first-line HAART to continue on their current treatment or switch to ritonavir-boosted PI monotherapy. Choice of PI is not specified and follow-up continues for five years.
- Arribas J et al. The MONET trial: darunavir/ritonavir monotherapy shows non-inferior efficacy to standard HAART, for patients with HIV RNA < 50 copies/mL at baseline. Oral abstract late breaker TUAB106-LB.
- Katlama C et al. Efficacy of darunavir/ritonavir as single-drug maintenance therapy in patients with HIV-1 viral suppression: a randomized open-label non-inferiority trial, MONOI-ANRS 136. Oral abstract late breaker WELBB102.
- PIVOT: Protease Inhibitor monotherapy Versus Ongoing Triple-therapy in the long-term management of HIV infection. MRC website.