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  9th International Congress on Drug Therapy in HIV Infection
Glasgow
November 9-13, 2008
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Salvage With Raltegravir, Etravirine, and Darunavir Works Fast in Small Case Series
 
 
  9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow
 
Mark Mascolini
 
Thirty of 32 heavily pretreated people starting raltegravir, etravirine, and darunavir/ritonavir had a viral load under 50 copies after 24 weeks of treatment in a single-center study from Palma de Mallorca, Spain [1]. The combination also had a good 24-week safety record, though all three of these drugs can cause rash.
 
This case series involved people who put together a rescue regimen including 400 mg of raltegravir twice daily, 200 mg of etravirine twice daily, and 600/100 mg of darunavir/ritonavir twice daily. Eight people also added nucleosides and 5 added enfuvirtide at some point in these 24 weeks, but no one was taking a nucleoside or enfuvirtide at week 24. (A more rigorous report might have described how long these people used enfuvirtide, whether they had used enfuvirtide before, why they stopped, and whether their responses differed from people who did not add enfuvirtide. Randomized trials show that first use of enfuvirtide in a background regimen can be an asset.)
 
The group had a median age of 44 years, 21 (66%) were men, 9 (28%) had AIDS, 9 (28%) had HCV infection, and 2 (6%) had HBV infection. These people had HIV infection for a median of 16 years and had taken antiretrovirals for a median of 13 years. Median number of previous regimens was 9, everyone had taken drugs in the first three antiretroviral classes, 14 (44%) people had a tipranavir failure on their record, and enfuvirtide failed in 16 (50%). Median CD4 count stood at 261 (interquartile range 134 to 415) and median viral load at 4.2 log (about 15,000 copies, interquartile range 3.6 to 4.7 log). Median number of primary protease inhibitor (PI) mutations stood at 5, and median tipranavir mutations at 4. But median starting darunavir mutations numbered only 1.
 
Twenty people (63%) had a viral load below 50 copies at week 4, as did 26 (81%) at week 12 and 30 (94%) at week 24. Of the 2 people without a load under 50 copies at week 24, 1 withdrew from the study at week 4 and the other had poor adherence. Three people started salvage with etravirine-related mutations, all had a Virco etravirine mutation score of 4.5, and all reached a viral load below 50 copies.
 
Rash flared in only 1 person 8 days after starting the salvage medley. The rash responded to steroids with no change in salvage drugs. The same person had an earlier cutaneous hypersensitivity reaction to nevirapine, and clinicians attributed the new rash to etravirine. Darunavir/ritonavir and raltegravir may also cause rash and (rarely) potentially fatal Stevens-Johnson syndrome. In a recent darunavir-raltegravir interaction study in healthy volunteers, 8 of 18 people (44%) had rash, and one case was serious [2]. Six people dropped out of that study because of rash.
 
Lipids rose through the 24-week study, especially in people who took any PI except atazanavir in their previous regimen. Triglycerides jumped by a median of 43 mg/dL by week 4, but by week 24 the median triglyceride gain stood at 14 mg/dL.
 
References
 
1. Imaz A, Villar del Saz S, Rivas MA. Raltegravir, etravirine and darunavir-ritonavir: a safe and successful rescue regimen in highly treatment-experienced HIV-1-infected patients. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract P040.
 
2. Anderson MS, Sekar V, Tomaka F, et al. Pharmacokinetic evaluation of darunavir/ritonavir and raltegravir in healthy subjects. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC), October 25-28, 2008, Washington, DC. Abstract A-962 (http://www.natap.org/2008/ICAAC/ICAAC_41.htm).