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Maintenance With Lower-Dose Darunavir in Virologically Suppressed
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15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, 19- 21 May 2014, Washington, DC
Mark Mascolini
Among people with a viral load below 50 copies, switching from 800 to 600 mg of ritonavir-boosted darunavir once daily yielded a noninferior 48-week virologic response rate compared with staying with 800 mg, according to results of a 100-person randomized trial in Barcelona [1]. Adverse event rates did not differ between study arms.
Licensed doses of certain antiretrovirals sometimes exceed doses that appeared to be effective in clinical trials. Lower doses may decrease side effect risks and save money. To see if a lower daily dose of the protease inhibitor darunavir would maintain viral suppression achieved with the standard dose, researchers in Barcelona randomized 100 people to continue taking 800/100 mg of darunavir/ritonavir daily or to switch to 600/100 mg daily.
All study participants had attained a viral load below 50 copies with standard-dose darunavir/ritonavir plus two nucleosides for at least 3 months. Everyone continued the same two nucleosides after randomization. No one had detectable darunavir-related resistance mutations or had taken a failing antiretroviral regimen.
The researchers defined failure as two consecutive viral loads above 50 copies or stopping treatment within 48 weeks of randomization. The trial had 80% power to show noninferiority of 600-mg darunavir if the lower bound of the 95% confidence interval (CI) for the difference in virologic response lay below -15% in the intention-to-treat noncompleter-equals-failure population.
Most study participants (81%) were men, and 20% had HCV coinfection. CD4 count at randomization averaged 562 (+/-303), with little difference between study arms. Age averaged 45.6 years in the 600-mg arm and 44.8 years in the 800-mg arm. Two thirds in each arm took tenofovir/emtricitabine, with the rest taking abacavir/lamivudine.
Three people randomized to 600 mg of darunavir and 2 randomized to 800 mg had confirmed virologic failure by week 48. One person in each arm did not reach week 48 because of loss to follow-up, and 1 person in the 600-mg arm died from cirrhosis and septic shock.
The Barcelona team figured that 90% in the 600-mg arm and 94% in the 800-mg arm had a week-48 viral load below 50 copies in the noncompleter-equals-failure analysis (difference -4%, 95% CI -12.9 to 4.9, P = 0.46). Thus the lower dose of darunavir was not inferior to the standard dose for maintenance therapy by this study's criteria. In an observed analysis, 94% randomized to 600 mg and 96% randomized to 800 mg had virologic suppression (difference -2.2%, 95% CI -9.6 to 5.2).
Darunavir trough concentrations were comparable with the two doses, and CD4 counts remained stable throughout the trial in both study arms. Adverse event rates were also similar in the two study arms. The researchers calculated that the lower dose would save about 1000 Euros ($1370) per patient-year.
Principal investigator Jose Molto (Hospital Universitari Germans Trias i Pujul) noted that he would use this low-dose maintenance strategy only for patients who had already demonstrated good antiretroviral adherence.
Reference
1. Molto J, Valle M, Ferrer E, et al. Reduced darunavir dose is as effective in maintaining HIV suppression as the standard dose in virologically suppressed HIV-infected patients. 15th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy. 19- 21 May 2014. Washington, DC. Abstract O_02.
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