Once-daily Boosted Darunavir (Prezista) in Treatment-experienced Patients with No Baseline Darunavir Resistance-associated Mutations

The second-generation protease inhibitor (PI) darunavir (Prezista), boosted with 100 mg ritonavir (Norvir) and used in conjunction with other antiretroviral agents, is indicated for the treatment of HIV infection in treatment-experienced adults, including those with HIV the has developed resistance to more than 1 other PI.

This indication is based on 24-week analyses of plasma HIV RNA levels and CD4 cell counts from 2 controlled trials of darunavir in combination with other antiretroviral drugs. Participants in both studies had clinically advanced disease, prior exposure to multiple drug classes (NRTIs, NNRTIs, and PIs), and evidence of HIV replication despite ongoing antiretroviral therapy.

The objective of the current study, published September 2, 2008 in the online edition of the Journal of Acquired Immune Deficiency Syndromes, was to examine the potential of once-daily dosing with darunavir/ritonavir 800/100 mg in treatment-experienced patients with no baseline darunavir resistance-associated mutations (RAMs).

Participants in the POWER 1 and 2 trials were treatment-experienced, with at least 1 primary PI resistance mutation as defined by the International AIDS Society-USA. In this analysis, virological and immunological responses were compared in patients with no baseline darunavir RAMs receiving darunavir/ritonavir 800/100 mg once daily (n = 23), darunavir/ritonavir 600/100 mg twice daily (n = 29), or other currently available PIs (n = 28) plus an optimized background regimen.

Results

• The proportions of patients achieving HIV RNA < 50 copies/mL at week 24 were 67% for the once-daily 800/100 mg darunavir/ritonavir and 62% for the twice-daily 600/100 mg group (P = 0.774).

• The rate of response in both darunavir/ritonavir arms was superior to that of the comparator PIs (11%; P < 0.0001).

• Mean HIV RNA change from baseline was 22.39 and 22.35 log10 copies/mL, respectively, for the darunavir/ritonavir once-daily and twice-daily arms (P = 0.895).

• Mean CD4 increases were 88 and 111 cells/mm3, respectively (P = 0.526).

In conclusion, the study authors stated that treatment-experienced, HIV-infected patients with no baseline darunavir RAMs achieved similar high responses with darunavir/ritonavir 800/100 mg once daily and 600/100 mg twice daily.

"This suggests that once-daily darunavir/ritonavir 800/100 mg therapy, which has been shown effective in treatment-naive patients and is currently being studied in treatment-experienced patients, shows potential in patients with no darunavir RAMs," they wrote.

In addition, they stated, "Although the results of this study suggest that darunavir/ritonavir 800/100 mg once daily is suitable for early treatment-experienced patients, a prospective, randomized trial is currently ongoing to further evaluate efficacy and safety of this dose in treatment-experienced patients."

"The long-term efficacy and safety data for darunavir/ritonavir 800/100 mg once daily in treatment-naive patients will be provided by the ongoing ARTEMIS trials," they added. "Results from this trial at 48 weeks provide further rationale to evaluate darunavir/ritonavir as an effective and more convenient once-daily regimen in earlier lines of therapy."

Note: The following points should be considered when initiating therapy with darunavir, according to the drug's product label:

• Treatment history and, when available, genotypic or phenotypic testing, should guide the use of darunavir.

• The use of other active agents with darunavir is associated with a greater likelihood of treatment response.

• The risks and benefits of darunavir have not been established in treatment-naive adult patients or pediatric patients.

Tibotec BVBA, Mechelen, Belgium.

9/19/08

Reference

SM De Meyer, S Spinosa-Guzman, TJ Vangeneugden, and others. Efficacy of once-daily darunavir/ritonavir 800/100 mg in HIV-infected, treatment-experienced patients with no baseline resistance-associated mutations to darunavir. Journal of Acquired Immune Deficiency Syndromes. September 2, 2008 [Epub ahead of print]. (Abstract).

Related Articles

1. C Katlama, R Espositi, JM Gatell, and others (for the POWERR 1 Study Group). Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. AIDS 21(4): 395-402. Feb 19, 2007.

2. B Clotet, N Bellos, JM Molena, and others (for the POWER 1 and 2 Study groups). Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomised trials. Lancet 369(9568): 1169-1178. April 7, 2007; Erratum in: Lancet 371(9607): 116. January 12, 2008.

3. R Ortiz, E Dejusus, H Khanlou, and others. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS 22(12): 1389-1397. July, 31, 2008.