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Activity of etravirine on different HIV-1 subtypes: Week 48 data of the pooled DUET trials and in-vitro susceptibility in treatment-naïve patients
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Reported by Jules Levin
9th International Congress on Drug Therapy in HIV Infection, Glasgow, UK, 9-13
November 2008
Johan Vingerhoets,1 Hilde Azijn,1 Lotke Tambuyzer,1 Inge Dierynck,1 Sandra De Meyer,1 Laurence Rimsky,1 Monika Peeters,1
Goedele De Smedt,1 Marie-Pierre de Béthune,1 Gaston Picchio2
1Tibotec BVBA, Mechelen, Belgium; 2Tibotec Inc., Yardley, PA, USA
AUTHOR CONCLUSION
In DUET, baseline disease characteristics (viral load, CD4, ETR FC, DRV FC) were similar between patients infected with different subtypes, except for a higher number of sensitive NRTIs used in those with HIV-1 subtype non-B
ETR was equally effective in suppressing viral replication in patients infected with HIV-1 subtype B or various HIV-1 non-B subtypes
-- the additional effect of ETR on virological response as compared to placebo was similar in patients infected with HIV-1 subtype B or various HIV-1 non-B subtypes
Further investigations were performed using HIV-1 recombinant clinical isolates from treatment-naïve patients infected with various HIV-1 subtypes
-- comparable median ETR FC values were observed irrespective of HIV-1 subtype
These data confirm the activity of ETR against a broad range of HIV-1 subtypes
Abstract
Etravirine (ETR; TMC125) has shown good in-vitro activity against primary HIV-1 group M isolates from different subtypes and has demonstrated durable efficacy in treatmentexperienced, HIV-1-infected patients in the Phase III DUET trials. In-vivo efficacy and in-vitro activity of ETR against different HIV-1 subtypes was further investigated.
DUET patients were randomised 1:1 to ETR (200mg bid) or placebo, both with a background regimen (BR) of NRTIs, darunavir (DRV) with low-dose ritonavir (DRV/r) and optional enfuvirtide (ENF). Subgroup analyses of the effect of HIV-1 subtype on the proportion of patients with viral load <50 HIV-1 RNA copies/mL (time-to-loss of virological response [TLOVR] imputation algorithm) were conducted on pooled Week 48 data. Genotype/subtype and phenotype determinations were performed using the vircoTYPE HIV-1 and AntivirogramTM assays, respectively. The effect of HIV-1 subtype on ETR fold-change in EC50 (FC) value was analysed in HIV-1 recombinant clinical isolates from treatment-naïve patients enrolled in other Tibotec trials (n=872) that included 49% of HIV-1 subtype non-B (18% CRF01_AE; 16% C; 5% A1; 3% CRF12_BF; 2% CRF02_AG; 1% F1; 3% other).
In DUET, HIV-1 subtype was available for 594 and 595 patients in the ETR and placebo arms, respectively. The majority of these (93.8%) harboured HIV-1 subtype B. Among the non-B subtypes, CRF12_BF (2.1%), F1 (1.2%), and CRF02_AG (0.8%) were most prevalent. Baseline disease characteristics (viral load, CD4, ETR FC, DRV FC, phenotypic sensitivity score [PSS]) were similar between patients with different subtypes, except for a higher number of
sensitive NRTIs used in those with HIV-1 subtype non-B. In the ETR arm, virological responses at Week 48 were 59.9% (336/561) for HIV-1 subtype B vs 72.7% (24/33) for all other HIV-1 subtype non-B, as compared to an overall response of 60.6%.
These data were further supported by in-vitro results that indicated a comparable median (interquartile range) ETR FC in virus isolates from treatment-naïve patients infected with subtype B or non-B (1.1, 0.8-1.6 or 1.2, 0.8-1.7), respectively.
In the DUET studies, ETR was equally effective in suppressing viral replication in patients infected with HIV-1 subtype B or non-B. Furthermore, both subtype B and non-B HIV-1 recombinant clinical isolates from treatment-naïve patients exhibited comparable levels of in-vitro phenotypic susceptibility to ETR. These results confirmed the broad activity of ETR against HIV-1.
Data have been updated since abstract submission.
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