Etravirine (TMC-125) associated with -1 log viral load reduction at 48-weeks results in treatment experienced patients

HIV Treat Bull - Vol. 7, No. 7/8, September 2006

Cal Cohen from Community Research Initiative of New England, Boston reported 48-week results from the Tibotec randomised, controlled, Phase II study of etravirine (TMC-125) in 199 treatment experienced patients with documented NNRTI resistance and 3 or more primary PI mutations.

Patients were randomised to TMC125 (400 mg or 800 mg bid) with an investigator selected background, or standard-of-care control regimen. Median baseline CD4 and viral load were 100 cells/mm³ and 4.7 log copies/mL respectively.

Mean reductions viral load (ITT, NC=F) were -0.88, -1.01 and -0.14 logs for the 400mg, 800mg and control arms respectively (p<0.05 for both TMC doses compared to control). CD4 cell counts increased by +58, +61 and +13 cells/mm³, for the 400mg, 800mg and control arms respectively.

The study design allowed patients with virological failure in the control group to leave the study after 16 weeks and access etravirine on an open-label basis. This confounded the comparison of safety by the lower median duration of treatment in the control arm of 17.9 weeks, versus 47.7 weeks in both TMC125 groups. Grade 3/4 side effects (all causes) were reported in 43% of patients on TMC125 and 17% patients discontinued etravirine due to side effects.

The principle importance of etravirine is the response to NNRTI-experienced patients. At baseline, patients had a median of 2 NNRTI mutations and the phenotypic median fold-change to efavirenz, nevirapine and etravirine was 41, 61, and 1.7-fold, respectively. The virologic response by number of NNRTI mutations at baseline is shown for the 800mg group is shown in Table 2.

Table 1: Results of etravirine (TMC-125) at 48-weeks

Table 2: Response to 800mg BID etravirine by baseline NNRTI resistance

No single NNRTI mutation was associated with an arbitrary >10-fold mean change, although clinical cut-offs for etravirine still have to be established from larger trials. 12% patients had a combination of mutations that generated >10-fold reduced susceptibility to etravirine, always including one or more from K101P, V179E/F, Y181I/V G190S and M230L, and always with at least 4 other mutations.

The dose selected for Phase III studies is 800mg BID, which requires 2 x200mg pills, twice-daily.

Reference

1. Cohen C, Steinhart C, Ward D et al. Efficacy and safety results at 48 weeks with the novel NNRTI, TMC125, and impact of baseline resistance on the virologic response in study TMC125-C223. Abstract TUPE0061.

2006-09-10
IB060709-09

©2008. I-BASE HIV Treatment Bulletin. Permission to reproduce courtesy of HIV i-Base, Third Floor East, Thrale House, 44-46 Southwark Street, London SE1 1UN - T: +44 (0) 20 7407 8488 F: +44 (0) 20 7407 8489

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2008. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2008. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content.