Once-daily darunavir/r monotherapy is suboptimal as initial regimen in treatment-naive people
Simon Collins, HIV i-Base
A tiny pilot for a Phase 2 study in treatment naive patients was stopped prematurely, concluding that once-daily darunavir/r was not sufficiently potent
as initial treatment in treatment naive patients for the study to continue.
Seven patients (with baseline viral load <100,000 copies/mL and CD4 counts >100 cells/mm3 and no evidence of drug resistance) were started on
open-label darunavir/r monotherapy. At week 4, all patients had >1 log drop in viral load and by week 8, viral load was <400 copies/mL in 4/7.
However, the trial was stopped as 5/7 patients had inadequate viral responses (together with the high level of screening failures – 38/45 screened – which
would limit enrollment for the larger planned study).
All seven patients achieved viral loads <50 copies/mL following intensification with nucleosides. CD4 responses at week 12 were +167 cells/mm3. No
grade 3-4 clinical or laboratory events were reported. No darunavir-associated mutations were seen in the two patients with genotype results.
Although these results were disappointing as initial therapy, an analysis of the MONET study that randomised people with undetectable viral load
(<50 copies/mL) on any HAART regimen to either darunavir/r as monotherapy or plus dual RTIs, reported non-inferiority (difference = 1.6; 95%CI 10.1 to
+6.8%) in terms of the percentage of people in each group with <50 copies/mL at week 48 (86.2% vs 87.8% respectively). 
These results were supported by other analyses, which is important for the continued use of darunavir/r in the currently enrolling MRC PIVOT study
of PI-monotherapy maintenance therapy. 
- Patterson P et al. A Phase II, open-label trial in treatment-naive. HIV-1-infected subjects who received DRV/RTV as induction monotherapy. 12th EACS, 11-14 November 2009, Cologne. Abstract PS4/4.
- Ripamonti D et al. Non-inferior efficacy shown across different efficacy endpoints in the MONET trial of darunavr/ritonaivr (DRV/r) monotherapy. 12th EACS, 11-14 November 2009, Cologne. Abstract PS 4/1.
- PIVOT: Protease Inhibitor monotherapy Versus Ongoing Triple-therapy in the long-term management of HIV infection.