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  51th ICAAC
Chicago, IL
September 17-20, 2011
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Randomized Switch From Suppressive PI to Etravirine Safe and Effective
  51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago

Mark Mascolini

Switching to the nonnucleoside etravirine from a protease inhibitor (PI) regimen that controlled HIV for at least 6 months maintained virologic suppression through 24 weeks in a small randomized trial in Barcelona [1]. Triglycerides and total cholesterol improved after the switch to etravirine.

Etravirine, the newest nonnucleoside, is licensed for antiretroviral-experienced adults with a detectable viral load and resistance to other nonnucleosides. The licensed dose is one 200-mg tablet or two 100-mg tablets twice daily, followed by a meal. Spanish researchers planned this pilot study to assess switching to etravirine from a suppressive PI regimen. All study participants had taken a triple-drug PI regimen for more than 12 months and had a viral load below 50 copies for more than 6 months.

Study participants in this ongoing 48-week trial could not have evidence of resistance to nucleoside or nonnucleoside reverse transcriptase inhibitors. All enrollees had at least one of the following three conditions: abnormal lipids (low-density lipoprotein [LDL] cholesterol above 130 mg/dL or triglycerides above 350 mg/dL), antiretroviral-related gastrointestinal problems, or low satisfaction with the current regimen.

The investigators randomized 24 people to switch the PI to etravirine (taken as 400 mg of tablet dissolved in water once daily) and 22 people to maintain their PI regimen. (US prescribing information says people who cannot swallow etravirine may dissolve tablets in a glass of water. The water should to stirred and swallowed immediately, then the glass should be rinsed several times with water and all the rinse water should be swallowed.)

Age averaged 47 years in both study arms, and about two thirds were men. The etravirine group had taken antiretrovirals for an average 8 years and the control group for an average 9.2 years. (These must have been highly adherent patients to take antiretrovirals so long without emergence of virus resistant to reverse transcriptase inhibitors.) CD4 counts when the trial began averaged about 700 in both study arms. About half of study participants wanted to quit their PI regimen to stop twice-daily dosing or to stop ritonavir.

All study participants maintained a viral load below 50 copies through 24 weeks of follow-up. Average CD4 count rose nonsignificantly in both treatment groups through 24 weeks, from 702 to 795 in the etravirine group (P = 0.177) and from 704 to 743 in the PI group (P = 0.107). CD4 percent rose significantly from 32% to 34% (P = 0.025) among people taking etravirine, though this gain may not be clinically meaningful.

Total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, and triglycerides did not change significantly in the PI group. Among people who switched to etravirine, average total cholesterol fell from 206 to 186 mg/dL (P = 0.037), average "good" HDL cholesterol fell from 52 to 48 mg/dL (P = 0.004), average "bad" LDL cholesterol rose nonsignificantly from 110 to 121 mg/dL (P = 0.759), and average triglycerides dropped from 168 to 107 mg/dL (P = 0.004). The investigators did not calculate total/HDL cholesterol ratio.

Median etravirine trough concentration stood at 577 ng/mL, and the trough did not fall below 4 ng/mL in anyone taking the nonnucleoside. (Etravirine trough concentration averaged 297 +/- 391 ng/mL in people taking etravirine with 600/100 mg of darunavir/ritonavir in phase 3 trials, according to full prescribing information.)

Two people stopped treatment because of side effects. One in the etravirine group quit because of gastrointestinal problems, and one in the control group quit because of high cholesterol.

A double-blind, placebo-controlled trial compared an immediate switch from efavirenz to etravirine with a delayed switch in 38 men with virologic control but with central nervous system side effects while taking efavirenz [2]. As in the Spanish study, everyone in both study arms maintained an undetectable viral load through 24 weeks. Rates of grade 2 to 4 adverse events, including insomnia, abnormal dreams, and nervousness, dropped significantly after the change to etravirine.


1. Echeverrķa P, Bonjoch A, Puig J, et al. Pilot study to assess the efficacy and safety of switching protease inhibitor to once-daily etravirine in HIV-1-infected subjects with viral suppression: ETRA-switch study. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H2-785.

2. Waters L, Fisher M, Winston A, et al. A phase IV, double-blind, multicentre, randomized, placebo-controlled, pilot study to assess the feasibility of switching individuals receiving efavirenz with continuing central nervous system adverse events to etravirine. AIDS. 2011;25:65-71.