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Twice-Daily Darunavir/Ritonavir to Replace Double-Boosted PIs
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12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
People who traded two ritonavir-boosted (double) protease inhibitors (PIs) for twice-daily ritonavir-boosted darunavir maintained virologic control for 24 weeks, preferred the simplification, and saved money, according to preliminary results of a pilot randomized trial [1].
Dual ritonavir-boosted PIs like lopinavir plus atazanavir gained support as a tactic to control viral replication in people with virus moderately resistant to PIs. But doubling up PIs can add side effects and certainly raises costs. US investigators planned a small pilot trial to see if people maintaining virologic control with dual boosted PIs could ease off to darunavir/ritonavir without sacrificing antiviral activity.
The study involved 24 people with a viral load below 400 copies for more than 12 weeks on any dual boosted PIs. Study participants had to be taking at least one antiretroviral from another class with their PIs. Calvin Cohen and coworkers randomized them to continue doubled-up PIs or to switch to 600/100 mg of darunavir/ritonavir twice daily for 48 weeks. At week 24, people who stayed with dual boosted PIs and maintained a viral load under 400 copies could change to darunavir/ritonavir. No one had detectable PI mutations when the study began, but the researchers did not check to see whether they might have relevant mutations on earlier genotypes.
The primary endpoint of the trial was a 24-week comparison of proportions in each treatment group with a viral load under 50 copies/mL. The investigators defined virologic failure as a confirmed load above 400 copies.
The treatment groups did not differ in demographics or disease stage when the trial began. Nineteen of 24 enrollees (79%) were men, and 16 (67%) were white. Median age stood at 50 years (range 31 to 64), and median CD4 count measured 553 (range 144 to 1207). Seven people were taking atazanavir/lopinavir, 7 saquinavir/lopinavir, 6 atazanavir/saquinavir, 3 fosamprenavir/lopinavir, and 1 nelfinavir/saquinavir (without ritonavir). Fourteen people (58%) were taking one nucleoside, 9 (38%) were taking two nucleosides, and 1 (4%) was taking raltegravir.
Everyone in both groups had a sub-50-copy viral load at week 24. By week 48, 1 person in the darunavir/ritonavir arm had two blips above 50 copies. That person's viral load became undetectable after the trial ended without a drug change. Three people in the control arm did not swap their two PIs for darunavir/ritonavir at week 24. Of the 9 who did cross over to darunavir/ritonavir, 1 person with HBV infection left the study with a sub-50 load at week 36 because of a grade 4 liver enzyme jump. Of the remaining 8 people, 1 had a confirmed load above 400 copies by week 48. CD4 counts did not change substantially in either arm.
The trial did not have the statistical power to discern lipid differences between the two treatment arms. However, triglycerides and "bad" low-density lipoprotein cholesterol waned marginally by week 24 in the darunavir/ritonavir arm while climbing slightly or staying flat in the control arm. No one in either group had grade 3 or 4 side effects by week 24.
On a -3 to +3 scale rating treatment preference, people who switched to darunavir/ritonavir gave their new regimen a median score of 3.0 (range 0 to 3) at week 24. The 9 control-arm participants who switched to darunavir/ritonavir gave their new regimen a median score of 2.5 (range 2 to 3) at week 48. Switching from two PIs plus ritonavir to darunavir/ritonavir saved an average $217 in wholesale cost per patient monthly.
Reference
1. Cohen C, Liporace R, de Jesus E, et al. Use of twice-daily darunavir as a substitution for dual-boosted PIs in virologically suppressed patients: primary endpoint results of a pilot randomized clinical trial. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract PS4/2.
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