3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

HIGH RATE OF VIROLOGICAL FAILURE DURING ONCE DAILY THERAPY WITH TENOFOVIR + DIDANOSINE 250MG + EFAVIRENZ IN ANTIRETROVIRAL NAÏVE PATIENTS – RESULTS OF THE 12 WEEK INTERIM ANALYSIS OF THE TEDDI TRIAL

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPp0306

van Lunzen J.¹, Schewe K.², Kuhlmann B.³, Hoffmann C.⁴, Stoll M.⁵, Dellamonica P.⁶, Prazuck T.⁷, Benech H.⁸, Taburet A.M.⁹, Delfraissy J.F.^9
1University Medical Center Eppendorf, Hamburg, Germany, ²Private Practice St. Georg, Hamburg, Germany, ³Private Practice, Hannover, Germany, ⁴University of Schleswig-Holstein Campus Kiel, Kiel, Germany, ⁵University Medical School, Hannover, Germany, ⁶CHU, Nice, France, ⁷CHR, Orleans, France, ⁸CEA, Gif-sur-Yvette, France, ⁹CHU Bicetre, Paris, France

BACKGROUND: OD therapy with TDF/ddI/EFV offers a potentially attractive ART regimen. Co-administration of TDF and ddI results in higher ddI exposure. The effects of reducing the ddI dose on intracellular triphosphate levels have not yet been extensively studied in vivo. As two recent prospective studies suggested high rates of virological failure in naïve pts. with high VL we performed an unplanned interim analysis at week 12. Patients and

METHODS: Of 46 ART-naïve pts. who were enrolled into this prospective single-arm trial, 39 received medication and completed week 12. VL and CD4 were measured monthly, plasma trough levels of TDF, ddI and EFV at week 4 and 12. Initial VL kinetics (days 0-7, 14, 21 and 56) and corresponding intracellular di-/triphosphate levels of Tenofovir and ddI were measured in 9 pts. in a 12-hour PK substudy.

RESULTS: Mean VL of 5.04 log₁₀ RNA copies at BL dropped to a mean of 1.96 log₁₀ at week 12. At this time 73% and 23% of patients achieved a VL reduction to <400 and <50 c/ml respectively (ITT). VL dropped to <400 c/ml in a mean of 51 days. Mean CD4 count increased from 288/µl at BL to 410/µl comparable to other ART regimens. However, 10/39 pts. (25%) demonstrated virological failure at week 12. GT analysis showed drug resistance mutations to NA (65R, 74I/V) or NNRTI (101E, 103N, 188C, 190S/E) over time. In two cases primary NNRTI mutations were detected at BL. 6/10 patients with virological failure had an initial VL >100.000 c/ml and CD4 <200 cells/µl.

CONCLUSIONS: OD TDF/ddI/EFV was safe and led to a strong CD4 cell recovery. However, an unexpected high rate of virological failure was observed in patients with high BL viral loads and low CD4 counts. Thus this regimen should not be recommended in these patients.

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Clinical | TuPp0306 | Jan Van lunzen
HIV drug resistance around the world

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