NATAP: TMC114+TMC125 for Multidrug Resistant HIV

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Here are the results of two small studies with TMC-125+TMC114 in combination in multi-drug resistance by Julio Montaner in Canada and Marta Boffito in London.

ICAAC: Week 24 Results and Baseline Phenotypic Susceptibility in Treatment Experienced Patients Initiating the Combination of TMC114/r and TMC 125 - (09/29/06)

Combination of TMC114/r and TMC125 in Patients with Multidrug Resistant HIV

Reported by Jules Levin

J Montaner, M , T Kakuda, G Larsen, B Woodfall, D Miralles, PR Harrigan

Montaner et al., XVI International AIDS Conference, Toronto, Canada, Aug 2006, Poster THPE0136

TMC114 and TMC125 are antiretroviral drugs with activity against HIV that is resistant to available PIs and NNRTIs, respectively. TMC114 is a PI & was approved in June and TMC125 is a NNRTI and is available through an Expanded Access Program from Tibotec.

5 Patients

o HIV+ adults

o extensive treatment experience with NRTIs/NtRTIs,

NNRTIs, and PIs

o evidence of drug resistance on genotypic testing

Medication regimens

TMC114 600 mg with ritonavir 100 mg twice daily

TMC125 200 mg twice daily

+/- NRTIs/NtRTIs

+/- enfuvirtide (T20)

PK analysis: Cmax, Cmin, Tmax, AUC-12h

AUTHOR CONCLUSIONS

o In 5 treatment-experienced patients with multidrug-resistant HIV

o Combination therapy including TMC114/r and TMC125 resulted in substantial VL declines and CD4 cell count increases over 20-24 wks

o 4/5 achieved HIV RNA <50 copies/mL

o No major safety concerns identified

o TMC114 and TMC125 plasma levels were generally comparable with data previously presented for HIV+ patients

o Combination of TMC114/r and TMC125 may present a viable treatment option for patients with multidrug-resistant HIV

Patient History and Current Regimen

Immunologic Responses

Virologic Responses

Mean (SD) PK Parameters for TMC125, TMC114, and RTV

AUTHOR CONCLUSIONS

o In 5 treatment-experienced patients with drug-resistant HIV

o Combination therapy including TMC114/r and TMC125 resulted in substantial VL declines and CD4 cell count increases over 20-24 wks

o 4/5 achieved HIV RNA <50 copies/mL

o No major safety concerns identified

o TMC114 and TMC125 plasma levels were generally comparable with data previously presented for HIV+ patients

o Combination of TMC114/r and TMC125 may present a viable treatment option for patients with multidrug-resistant HIV