Durable efficacy and long-term safety of antiretroviral therapy are important goals in the management of treatment-experienced patients. The 96-week efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine were evaluated in the Phase III DUET trials.
Methods
HIV type-1-infected treatment-experienced adults with viral loads >5,000 copies/ml and NNRTI and protease inhibitor resistance were randomized to receive etravirine 200 mg or placebo, each twice daily and in combination with a background regimen of darunavir/ritonavir twice daily, nucleoside/nucleotide reverse transcriptase inhibitors and optional enfuvirtide. The primary end point was the proportion of patients with viral load <50 copies/ml (intent-to-treat analysis, time-to-loss of virological response algorithm) at week 24. Results from both trials were combined in the pre-specified pooled 96-week analysis.
Results
In total, 599 patients received etravirine and 604 received placebo. At week 96, 57% of patients in the etravirine group versus 36% in the placebo group had a viral load <50 copies/ml (P<0.0001); 91% and 88% of patients, respectively, had maintained this response from week 48. Mean increases in CD4+ T-cell count from baseline at week 96 were 128 cells/mm3 with etravirine versus 86 cells/mm3 with placebo (P<0.0001). With the exception of rash, which was reported more frequently with etravirine than placebo (21% versus 12%, respectively; P<0.0001), the safety and tolerability profile of etravirine was similar to placebo over the treatment period.
Conclusions
Etravirine, in combination with an antiretroviral background regimen, provided durable virological and immunological responses with no new safety concerns in treatment-experienced patients over 96 weeks in the DUET trials.
References
1.
MadrugaJ.V., CahnP., GrinsztejnB.Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial.Lancet2007; 370: 29–38.
2.
LazzarinA., CampbellT., ClotetB.Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial.Lancet2007; 370: 39–48.
3.
KatlamaC., HaubrichR., LalezariJ.Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled week 48 analysis of two randomized, controlled trials.AIDS2009; 23: 2289–2300.
4.
JohnsonV.A., Brun-VezinetF., ClotetB.Drug resistance mutations in HIV-1: fall 2005.Top HIV Med2005; 13: 125–131.
5.
TambuyzerL., VingerhoetsJ., AzijnH.Development of a list of mutations associated with NNRTI resistance for use in clinical research.5th European HIV Drug Resistance Workshop. 28–30 March 2007, Cascais, Portugal. Abstract 67.
6.
VingerhoetsJ., TambuyzerL., AzijnH.Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the DUET studies.AIDS2010; 24: 503–514.
7.
TambuyzerL., VingerhoetsJ., AzijnH.Characterization of genotypic and phenotypic changes in HIV-1-infected patients with virologic failure on an etravirine-containing regimen in the DUET-1 and DUET-2 clinical studies.AIDS Res Hum Retroviruses2010; in press.
Yazdanpanah Y, Fagard C, Descamps D, et al.High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial.Clin Infect Dis2009; 49: 1441–1449.
11.
NozzaS., ViscoF., SoriaA.Excellent short-term CD4 recovery with a PI- and NRTI-sparing regimen in triple-class failure HIV-infected patients: raltegravir, maraviroc, etravirine.9th International Congress on Drug Therapy in HIV Infection. 9–13 November 2008, Glasgow, UK. Abstract P45.
12.
TownerW., LalezariJ., SensionM.G.Efficacy, safety, and tolerability of etravirine with and without darunavir/ ritonavir or raltegravir in treatment-experienced patients: analysis of the etravirine early access program in the United States.JAIDS2010; 53: 614–618.
13.
ThompsonM.A., AbergJ.A., CahnP.Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society–USA panel.JAMA2010; 304: 321–333.
14.
Panel on Antiretroviral Guidelines for Adult and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. (Updated 1 December 2009. Accessed 10 January 2010.) Available from http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
