1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP
October 25 - 29, 2003 Warsaw, Poland
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9TH EUROPEAN AIDS CONFERENCE (EACS) 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP October 25 - 29, 2003 Warsaw, Poland |
| 7.3 Phase III/IV Trials F7/2 - VIROLOGIC DETERMINANTS OF 24-WEEK EFFICACY OF ATAZANAVIR WITH OR WITHOUT RITONAVIR IN PATIENTS WITH PRIOR FAILURE ON A PROTEASE INHIBITOR |
| (1) Fundacion Huesped, Buenos Aires, Argentina,2 Instituto di Ricovero e Cura a Carattere Scientifico S. Raffaele, Milan, Italy,3 Hospital Teodoro Alvarez, Buenos Aires, Argentina,4 Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil,5 Hospital Gabriel Mancera, IMSS, D.F., Mexico,6 Guillermo Almenara Hospital, Lima, Peru,7 Bristol-Myers Squibb Company, Waterloo, Belgium,8 Bristol-Myers Squibb Company, Wallingford, CT, USA |
Background of Study: Two randomized trials in PI-experienced HIV-infected patients evaluated efficacy of once-daily atazanavir (400 mg) combined with 2 NRTIs (Study 043, N=150), or atazanavir boosted with ritonavir (300/100 mg) combined with tenofovir and 1 NRTI (Study 045, N=120). Subjects in 045 had a more extensive antiretroviral history and had failed ³ 2 regimens containing all 3 classes of ARV.
Objectives: Exploratory analyses were performed to determine if baseline antiretroviral sensitivities and viral mutations correlated to antiviral effects of atazanavir regimens.
Methods: Changes in HIV RNA levels at Week 24 were examined in patients with baseline isolates: fully sensitive (£2.5 x IC50 of control) or resistant (>2.5 x IC50 of control) to atazanavir; with <4 or ³4 NRTI mutations; with <4 or ³4 PI mutations.
Results: Mean reductions in HIV RNA levels (log10 c/mL) at 24-weeks were: -1.82 with ATV-sensitivity (n=92) and -1.40 with ATV-resistance (n=34) in 043, and -2.16 (n=84) and -0.94 (n=28), respectively, in 045; -1.78 with <4 NRTI mutations (n=109) and -1.14 with ³4 NRTI mutations (n=21) in 043, and -1.99 (n=68) and -1.65 (n=44), respectively, in 045; -2.23 with <4 PI mutations (n=78) and -1.00 with ³4 PI mutations (n=34) in 045. In 043, only 26% of patients had ³4 PI mutations, and no subanalysis was performed.
Conclusions: In extensively pretreated patients, response to atazanavir correlated positively with baseline atazanavir sensitivity and was inversely related to the number of baseline NRTI and PI viral mutations. Small subgroup numbers and differences between study populations limited these analyses.
Presenting Author: Dr. Carlos Zala, Fundacion Huesped, 1202 Buenos Aires, 3932, Buenos Aires, Argentina, Phone: 54 11 4981 7777
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