H-520/341

1. Results 2: Percentage of patients demonstrating virologic response (ITT DC=F ) H-520/341 E-mail: dauerb@hivcenter.de Virologic Response to Tenofovir DF (TDF) Plus Trizivir (TZV) Therapy in Heavily Antiretroviral (ART)-Experienced, HIV+ Patients: 24 Week Results Background:We investigated the virologic and immunologic responses to a simple, mono-class, NRTI-only combination therapy consisting of TDF and TZV in heavily ART-experienced patients. Methods:A search through our database of all therapy-experienced patients taking TDF/TZV who had at least one lab value after start of therapy and 24 weeks of follow-up produced a dataset of 116 patients who met this criteria. CD4 count, viral load, ART history, and genotypic profiles were investigated. Baseline and previous nucleoside-associated resistance mutations were studied for patterns correlated with response or non-response. Virologic response was defined as viral load levels less than 400 copies/ml at week 24. Sub-group analyses also included percentage of patients with <50 copies/ml. Response: Median viral load decreased from 400 copies at baseline to 87 copies/ml at week 24; median CD4 count increased from 283 to 315 cells/mm³. In an ITT analysis (DC=F), 70/116 (60%) responded to TDF+TZV therapy (<400 copies) and 40 had <50 copies/ml. 60/116 patients had viral loads of 400 or less copies at baseline; 55/60 were able to maintain undetectable viral loads. Of the 17 pts who discontinued, 8 had <400 copies and 6/8 had <50 copies at time of therapy stop. 27 pts had ≥100,000 copies/ml at baseline. At week 24, median viral load was 1040 copies/ml. 12/27 (44%) had a virologic response to TDF+TZV. 24/27 had genotypes available. 84/116 patients had genotype resistance tests available before starting TDF/TZV therapy. 74/84 had previous genotype tests available for analysis, but due to low viral loads at baseline, many patients had no baseline genotypes. Therefore, statistical analysis was performed for archived mutations. Non-response was defined as >50 copies/mlfor this analysis. - 46/84 had a minimum of 3 (3-10) NRTI resistance-associated mutations. Despite the magnitude of resistance mutations, median viral load at week 24 for this sub-group of 46 patients was 400 copies - reduced from 10,000 copies at baseline. Results:Baseline characteristics are shown in the table. The patients were generally doing well, and about half were switched to TDF/TZV for simplification purposes or due to toxicities while the other half were experiencing virologic failure with other regimens. Follow up is a median 51 weeks (range 3-301). 99/116 (85%) pts were still on TDF/TZV therapy at week 24. Reasons for discontinuation: 7 virologic failures, 1 hepatotoxicity, 5 gastrointestinal events, 4 other (pregnancy, lost to follow up, patient choice). Brenda Dauer*1, Martin Stuermer1, Axel Mueller1, Peter Gute2, Stephan Klauke3, Pavel Khaykin1, Schlomo Staszewski1 1 JW Goethe University Hospital, Frankfurt, Germany; 2 HIV Specialty Private Practice, Frankfurt, Germany; 3 Internistisches Facharztzentrum Stresemannallee, Frankfurt, Germany The 210W always presented in combination with the 215Y/F. The 215 however, did emerge without the 210. • CONCLUSIONS: • Patients heavily pre-treated with nucleoside analogues may show response to monoclass TDF+TZV therapy despite having a history of failure with NRTIs. • Lower baseline viral load, higher baseline CD4 count and fewer ART drugs taken in past were associated with response. • Archived 215 Y/F or 210W + 215Y/F mutationswere significantly associated with non-response. • Further evaluation of TDF+TZV regimen as a backbone in salvage therapy is warranted.