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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KeywordsViral Load Virological Response Etravirine Enfuvirtide Phenotypic Susceptibility
Purpose of the study
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 treatment-experienced, HIV-1 infected patients in the Phase III DUET trials. In vivo efficacy and in vitro activity of ETR against different HIV-1 subtypes were further investigated.
DUET patients were randomized 1:1 to ETR (200 mg BID) or placebo, both with a background regimen of NRTIs, darunavir/ritonavir and optional enfuvirtide. Subgroup analyses of the effect of HIV-1 subtype on the proportion of patients with viral load (VL) <50 HIV-1 RNA copies/mL (TLOVR imputation algorithm) were conducted on pooled week 48 data. Genotype/subtype and phenotype determinations were performed using the Virco® TYPE HIV-1 and Antivirogram™ assays, respectively. The effect of HIV-1 subtype on ETR fold change in EC50 value (FC) was analyzed 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).
Summary of results
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 (VL, CD4, ETR FC, DRV FC, 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 (IQR) 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.
This article is published under license to BioMed Central Ltd.