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A phase 4, single-arm, open-label, pilot study of maraviroc, raltegravir and darunavir/r in HIV-1 adults with triple class failure: TERCETO study

Poster Abstract – P283

A phase 4, single-arm, open-label, pilot study of maraviroc, raltegravir and darunavir/r in HIV-1 adults with triple class failure: TERCETO study

Patterson, P; Magneres, C; Sued, O; Fink, V; Figueroa, M; Cesar, C; Gun, A; Cahn, P and Krolewiecki, A

Fundación Huésped, Department of Clinical Research, Buenos Aires, Argentina.

Abstract

The purpose of this phase 4, single-arm, open-label study was to evaluate the safety, tolerability, efficacy, antiviral and immunological activity of maraviroc (MVC) in combination with raltegravir (RGV) and darunavir/r (DRV/r) in adult HIV-1 infected patients (pts) with limited treatment options. HIV-1 pts with documented virologic triple class failure or multi-drug class resistance defined as the presence of Q151 complex, 69 insertion complex and/or≥3 TAMs for NRTIs and K103N, G190S+Y181C or Y188L mutants for NNRTIs and≥3 RAMs (L10F/I/R/V; M46I/L; I54V/M/L; V82A/F/T/S; I84V; L90M) for protease inhibitors (PIs) were offered a triple drug regimen consisting of MVC 150 mg BID, RGV 400 mg BID and DRV/r 600/100 mg BID. Safety, lipid profile and virologic efficacy were evaluated at week 4, 12, 24, 36 and 48. Between January 2010 and March 2012, 27 pts were enrolled. Screening failure rate was 52% due to undetectable viral load (pVL) or non R5 tropism type (Trofile™). Despite being heavily pre-treated pts, only 26% had negative tropism test at SCR. Baseline characteristics of 13 included pts were: 77% male, median age 43 years (IQR: 40.1–48.6), 38% had a prior AIDS-defining condition. Median BSL pVL was 23,350 cps/mL (4.4 log10) (IQR: 11,236–55,785) and median CD4 was 222 cells/mm3 (IQR: 179–318). Median time on NRTIs, NNRTIs and PIs were 10.7 (8.6–13.7), 1.7 (1.3–7.6) and 5.4 (4.7–10) years respectively. Pts had received a median of 2 PIs (IQR: 2–3). 8/13 pts showed thymidine analogue-associated mutations (TAMs), and≥2 were present in 5/13. Detectable NNRTI resistance-associated mutations (RAMs) were present in 10/13 patients. 9/13 had≥4 primary PI RAMs. At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis)=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1) and the remaining pts (11/13) achieved undetectable pVL and increased CD4 in 133 cell/mm3 from BSL (IQR: 81–174.5). Median total cholesterol levels increased from 162 mg/dL (IQR: 135-188) to 215 mg/dL (IQR: 182–237) between BSL/W48; median change in cholesterol levels: 40 mg/dL (IQR: 6.5-66). Salvage therapy including MVC, RGV and DRV/r achieved sustained reductions in pVL (<50 copies/mL) through 48 weeks of therapy in this pilot study with no treatment limiting toxicity.

Acknowledgements

TERCETO study was sponsored through an investigator-initiated research (IIR) grant from Pfizer Inc. Merck provided raltegravir.

Published 11 November 2012

Copyright: © 2012 Patterson P et al; licensee International AIDS Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection
Patterson P et al. Journal of the International AIDS Society 2012, 15(Suppl 4):18268
http://www.jiasociety.org/index.php/jias/article/view/18268 | http://dx.doi.org/10.7448/IAS.15.6.18268

 



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