12th Annual Conference of the British HIV Association 29 March–1 April 2006, Brighton, UK

PHARMACOKINETICS (PK) AND ANTIRETROVIRAL (ARV) RESPONSE TO TMC-114/R AND TMC-125 COMBINATION IN PATIENTS WITH HIGH-LEVEL VIRAL RESISTANCE

HIV Med 2006; 7(Suppl. 1):3 (abstract no. O10)

Akil Jackson¹, Marta Boffito¹, Alan Winston¹, Carl Fletcher¹, Anton Pozniak¹, Mark Nelson¹, Graeme Moyle¹, Desmond Maitland¹, Izabela Tolowinska¹, Richard Hoetelmans², Diego Miralles² and Brian Gazzard^1
1Chelsea and Westminster Hospital, London, UK, ²Tibotec BVBA, Mechelen, Belgium

BACKGROUND: In patients with three-class HIV resistance, combinations of investigational ARVs may represent the only therapeutic option. TMC-114 and TMC-125 are potent investigational ARVs with activity in naïve and experienced patients. However, the drug interaction between these agents has not been characterised in HIV patients.

METHODS: Multi-class-experienced HIV patients with documented three-class resistance were enrolled into a study to investigate the PK, safety and efficacy of TMC-114/r 600/100 mg bid and TMC-125 200 mg bid (new formulation) plus NRTIs with or without enfuvirtide (ENF). TMC-114/r/TMC-125 steady-state PK was assessed over 12 h. HIV resistance, safety and efficacy were assessed. PK parameters were compared to historical data; associations with virological response were assessed by linear regression analysis.

RESULTS: 10/11 patients completed both PK phases; median (range) baseline characteristics included age 43 (38–56) year; CD4 75 (3–490) cells/µl; log₁₀ viral load (VL) 4.6 (3.9–5.5); N of mutations (IAS, October 2005) for PI, primary 4 (0–5) and resistance associated 11 (2–13), for NRTI 7 (2–9), and for NNRTI 2 (0–6). PK parameters measured on day 28 reflected unchanged exposure to TMC-114 and modestly reduced (30%) exposure to TMC-125 when compared to historical controls. At week 12, all patients had achieved at least a 2 log₁₀ decrease in HIV-RNA with a median of (2.76; all had VL<400 (8<40). Median CD4 increase was 87 cells/µl. No serious adverse events or changes in laboratory safety were reported.

CONCLUSIONS: No clinically significant PK interaction between TMC-114 and TMC-125 was observed. The combination was well-tolerated and showed impressive short-term efficacy against three-class-resistant HIV. Studies of this combination are warranted.

2006-03-29
O10

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