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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

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.

Methods

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.

Conclusion

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.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Vingerhoets, J., Azijn, H., Tambuyzer, L. et al. Activity of etravirine on different HIV-1 subtypes: week 48 data of the pooled DUET trials and in vitro susceptibility in treatment-naïve patients. JIAS 11 (Suppl 1), P189 (2008). https://doi.org/10.1186/1758-2652-11-S1-P189

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  • DOI: https://doi.org/10.1186/1758-2652-11-S1-P189

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