Medical Advocates for Social Justice
Conference Abstract

5th International Congress on Drug Therapy in HIV Infection
Glasgow, Scotland, October 22-26, 2000

ABT-378/Ritonavir (ABT-378/r) vs. Nelfinavir in Antiretroviral-Naïve Subjects: Week 48 Comparison in a Phase III Blinded Randomized
Clinical Trial

M. JOHNSON1G. BEALL, A. BADLEY, W. CAMERON, D. JOHNSON, P. RUANE, R. RUBIO, R. STRYKER, S. WALMSLEY, M. KING, P. CERNOHOUS, J. MOSELEY, M. OPFERMAN,
M. SATTLER, B. BERNSTEIN AND E. SUN for the M98-863 Study Team.

 

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ABT-378/r is a novel protease inhibitor (PI) that achieves trough concentrations >75-fold above the EC50 of ABT-378 relative to wild type virus when dosed at 400/100 mg BID. A phase II study of ABT-378/r demonstrated activity in ARV-naïve subjects; 96% had VL<400 copies/mL at Week 96 (OT) with 2/100 discontinuing for study drug-related AEs.

Study M98-863 is a 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 at standard doses. There were no significant differences between the two treatment groups in baseline HIV RNA (overall mean 4.9 log10 copies/mL) and CD4 cell count (overall mean 259 cells/m L).

Week 40

Week 48*

ABT-378/r

NFV

ABT-378/r

NFV

HIV RNA <400 (OT)

94%‡

82%‡

94%‡,*

82%‡,*

HIV RNA <400 (ITT M=F)

79%‡

64%‡

*

*

HIV RNA <50 (OT)

84%‡

71%‡

87%‡,*

69%‡,*

HIV RNA <50 (ITT M=F)

70%‡

54%‡

*

*

CD4 change from BL (cells/m L)

189

178

*

*

Discontinuations (total)

14%

19%

*

*

* Preliminary data; complete Week 48 data will be presented.
‡ p-value < 0.001 comparing ABT-378/r group to NFV group

Genotypic and phenotypic analyses were performed on subjects with incomplete virologic suppression at Week 24. Of samples analyzed to date, 0/18 ABT-378/r subjects and 14/ 35 NFV subjects demonstrated evidence of phenotypic or genotypic resistance to the PI.

AEs occurring in >2% of subjects included diarrhea, nausea, asthenia, abdominal pain, vomiting, and headache. The incidence rates of these events were similar between the two treatment groups. The most common laboratory abnormalities were triglyceride and cholesterol elevations. Through Week 40, 2% and 3% of subjects in the ABT-378/r and NFV groups, respectively, had discontinued due to PI-related AEs.

A significantly greater proportion of ABT-378/r treated subjects achieved HIV RNA below the LOQ in all analyses at Weeks 40 and 48. Both regimens were well tolerated, as manifested by the low incidence of study drug-related discontinuations through week 40.

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ABT-378/RITONAVIR (ABT-378/r) vs. Nelfinavir in Antiretroviral-Naïve Subjects: Week 48 Comparison in a Phase III Blinded Randomized Clinical Trial.

© 2000 Medical Advocates for Social Justice