Medical Advocates for Social Justice


Medical Advoates for Social Justice

40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
 Toronto, Canada,
 September 17-20, 2000

Abstract: Efficacy of ABT-378/r vs Nelfinavir (NFV) in Antiretroviral (ARV)-Naïve Subjects: Results of a Phase III Blinded Randomized Clinical Trial

S. WALMSLEY1, A. BADLEY2, G. BEALL 3, W. CAMERON2, D. JOHNSON4, M. JOHNSON5, P. RUANE6, R. RUBIO7, R. STRYKER8, M. KING9, P. CERNOHOUS9, J. MOSELEY9, M. OPFERMAN9, M. SATTLER9, B. BERNSTEIN9, AND E. SUN9

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Background: ABT-378/r is a novel protease inhibitor that achieves trough (pre-dose) concentrations that exceed the EC50 of ABT-378/r against wild type HIV by >75 fold when dosed at 400/100 mg BID. A phase II study has demonstrated activity in ARV-naïve subjects with 98% achieving HIV RNA <400 copies/mL at Week 72 (OT) with 1/100 discontinuing for study drug related adverse events.

Methods: Multi-center, international, double-blind randomized study of 653 (129 female) ARV-naïve subjects treated with either ABT-378/r 400/100 mg BID (N=326) or NFV 750 mg TID (N=327). All subjects also received d4T and 3TC.

Results: Baseline characteristics included mean/range HIV RNA (log10) 4.9/2.6-6.8 (ABT-378/r) and 4.9/2.8-6.8 (NFV), and mean/range CD4 (cells/µL) of 260/2-944 (ABT-378/r) and 258/3-949 (NFV). Disposition through week 24 is summarized below.

 

ABT-378/r

NFV

p-value
HIV RNA< 400 copies/mL (OT) 92% 81% <0.001*
HIV RNA< 400 copies/mL (ITT M=F) 79% 71% 0.015*

Kaplan-Meier estimate of proportion still responding at week 24

 90% 77% <0.001†
Discontinuations (total) 11% 12% NS
*p-value based on Pearson’s chi-square test
†p-value based on Cox proportional hazards model

Protease inhibitor-related moderate/severe adverse events occurring in >2% of subjects in either treatment group included diarrhea, nausea, asthenia, abdominal pain, vomiting, and headache. No differences were observed between treatment groups. A slightly higher rate of Grade 3/4 cholesterol and triglyceride elevations was seen in the ABT-378/r group compared to the NFV group (7% vs 3% and 5% vs 1%, respectively).

Conclusions: A significantly greater proportion of ABT-378/r treated subjects achieved HIV RNA < 400 copies/mL at week 24. Both regimens were well tolerated.

1Toronto Gen. Hosp., Toronto, Canada, 2Ottawa Gen. Hosp., Ottawa, Canada, 3Harbor-UCLA Med. Ctr., Torrance, CA, 4Bedford Gardens, South Africa, 5The Royal Free Hosp. London, UK, 6Tower Infectious Diseases, Los Angeles, CA, 7Hosp. Doce de Octubre, Madrid, Spain, 8Pacific Oaks Res., Beverly Hills, CA, 9Abbott Laboratories, Abbott Park, IL.

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 Efficacy of ABT-378/r vs Nelfinavir (NFV) in Antiretroviral (ARV)-Naïve Subjects:
Results of a Phase III Blinded Randomized Clinical Trial
© 2000 Medical Advocates for Social Justice