In the POWER 1 (TMC114-C213) and 2 (TMC114-C202) 24-week primary analysis, darunavir (Prezista) combined with low-dose ritonavir (darunavir/r) demonstrated better antiviral activity than control PIs (CPIs) in treatment-experienced patients.

In an oral presentation, Sharon Walmsley of Toronto General Hospital reported data from patients who had reached 48 weeks of treatment in an ad hoc (unplanned) pooled analysis from the POWER 1 and POWER 2 studies.

The highest dose (600/100mg bid) provided the greatest virologic response. The combined 48-week analysis of these trials assesses long-term efficacy and safety of darunavir/r 600/100mg bid versus CPIs.

In both trials, PI-, NRTI- and NNRTI-experienced patients with one baseline primary PI mutation were randomized to receive an optimized background regimen plus one of four darunavir/r doses or boosted CPI.

Virologic response and adverse events (AEs) in patients initially randomized to darunavir/r 600/100mg bid and CPIs were compared at Week 48 (ITT-TLOVR).

The primary efficacy parameter was the proportion of patients with 1 log10 viral load reduction.

Results

At the recommended dose for treatment-experienced patients, TMC114/r achieved significantly higher virologic response rates than CPIs at Week 48, similar to those observed at Week 24 (table).

24-week Primary Analysis Findings

• 69.5 percent vs. 21 percent achieved a virologic response defined as equal to or greater than 1.0 log10 reduction (90 percent reduction) in viral load from baseline
• 45 percent vs. 12.1 percent achieved undetectable viral load (less than 50 copies/mL)
• CD4+ cell mean increase of 92 cells/mm3 vs.17 cells/mm3 from baseline

Analysis of Patients Reaching 48 Weeks of Treatment

Among 110 patients who had reached 48 weeks of treatment in the darunavir/r arm (total n=131) vs. 120 patients who had reached 48 weeks of treatment in the control arm (total n=124), intent-to-treat data will be presented:

• 61 percent vs. 15 percent had a virologic response defined as equal to or greater than 1.0 log10 reduction (90 percent reduction) in viral load from baseline
• 46 percent vs. 10 percent reached undetectable viral load (less than 50 copies/mL)
• CD4+ cell mean increase of 102 cells/mm3 vs.19 cells/mm3 from baseline

Among patients reaching 48 weeks, the most commonly reported adverse events among patients in the darunavir/r arm vs. control arm were diarrhea (20 percent vs. 28 percent), nausea (18 percent vs. 13 percent), headache (15 percent vs. 20 percent), nasopharyngitis (14 percent vs. 11 percent) and fatigue (12 percent vs. 17 percent).  Discontinuations because of adverse events were seven percent in the darunavir/r arm vs. five percent in the control arm. 

Longer-term data are required to further evaluate the safety and efficacy of darunavir/r.

In conclusion, the authors state, “Darunavir/r TMC114/r has demonstrated sustained efficacy in this treatment-experienced population. Its tolerability profile is similar to that of CPIs, with a lower incidence of diarrhea.

Clinic of Infectious Diseases, Milano, Italy, Universidade Federal de Paraná, Parana, Brazil, University of Pennsylvania, Philadelphia, United States, University Hospital, Bonn, Germany, University Health Network, Toronto General Hospital, Toronto, Canada, Tibotec BVBA, Mechelen, Belgium, Tibotec Inc., Yardley, USA.

FDA Indication for Darunavir

Darunavir, co-administered with 100 mg ritonavir (darunavir/r) and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.

This indication is based on Week 24 analyses of plasma HIV RNA levels and CD4+ cell counts from two controlled trials of darunavir/r in combination with other antiretroviral drugs. Both studies were conducted in clinically advanced, treatment-experienced (NRTIs, NNRTIs, and PIs) adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with darunavir/r:

• Treatment history and, when available, genotypic or phenotypic testing should guide the use of darunavir/r.
• The use of other active agents with darunavir/r is associated with a greater likelihood of treatment response.
• The risks and benefits of darunavir/r have not been established in treatment-naïve adult patients or pediatric patients.