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Dual Combo of Darunavir/Ritonavir and Etravirine Assessed in London Clinic
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Tenth International Congress on Drug Therapy in HIV Infection, November 7-11, 2010, Glasgow
Mark Mascolini
Twenty-one people who switched from other regimens to once-daily darunavir/ritonavir plus etravirine enjoyed good CD4 gains over almost 1 year of follow-up and sustained viral suppression, according to a retrospective analysis from London's Royal Free Hospital [1]. The Royal Free clinicians proposed that this nucleoside-sparing duo deserves consideration because of its combined high genetic barrier to resistance and good pharmacokinetic profile.
The study involved 21 people who changed their antiretrovirals to once-a-day darunavir/ritonavir (800/100 mg) plus etravirine (400 mg): 13 wanted to simplify a dual-protease inhibitor (PI) regimen (plus one or more nucleosides or a nonnucleoside), 7 wanted to stop nucleosides because of toxicities, and 1 had to change from a failing combination of zidovudine/lamivudine plus nevirapine. Five people had prior mutations only to nucleosides, 1 had only the K103N nonnucleoside mutation (which by itself does not confer resistance to etravirine), 1 had both nucleoside mutations (K65R and M184V) and a nonnucleoside mutation (Y181C, which is an etravirine-related mutation), and 1 had two PI mutations (I54V and I84V) plus thymidine nucleoside analog mutations and M184V.
During follow-up, 4 people (19%) stopped the new combination, 1 who had gastrointestinal side effects, 2 who further simplified to darunavir/ritonavir monotherapy, and 1 with poor adherence in whom the Y181C mutation developed and who traded etravirine for abacavir/lamivudine plus darunavir/ritonavir.
Before the switch to darunavir/ritonavir plus etravirine, 19 people (90%) had a viral load below 50 copies and the remaining 2 had a sub-1000 load. Among 18 people who took the dual-drug regimen for at least 24 weeks, 17 maintained a viral load below 50 copies and 1 changed to darunavir/ritonavir monotherapy and stayed under the 50-copy mark. All 9 people who had more than 48 weeks of follow-up on darunavir/ritonavir plus etravirine maintained a sub-50 viral load.
CD4 counts averaged 623 (range 269 to 1005) upon switching to the double regimen. Among 16 people with at least 24 weeks of follow-up and a CD4 count after that, the average CD4 gain was 59. Nine people who had more than 48 weeks of follow-up added an average 153 CD4 cells on the new combination. Lipid measurements 24 weeks after the switch showed no meaningful shift in total cholesterol, high-density lipoprotein cholesterol, or triglycerides.
Simplifying to the double-drug combination saved an average 202 British pounds per patient monthly, mainly because of the switch from a double-PI regimen. The Royal Free team calculated a total savings of 45,400 pounds over 226 patient-months, again mainly because so many people dropped a double-PI regimen.
The investigators plan longer follow-up that will include more people who switch to this combination to confirm its virologic and immunologic efficacy.
Reference
1. Tyrer M, Swaden L, Marshall NJ, Johnson M. Switching to dual therapy with darunavir/ritonavir and etravirine: a simplification strategy. Tenth International Congress on Drug Therapy in HIV Infection. November 7-11, 2010. Glasgow. Abstract P051.
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