5th Report from: 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, Tuesday Feb 1

ABT-378/ritonavir in Treatment-NaÔve: 72 Week Update

Trip Gulick, with Cornell University, reported for the study team. This study is ongoing phase 2, randomized, double-blind trial of ABT-378 in combination with d4T and 3TC. To qualify patients had to have >5000 copies/ml viral load, and at baseline median viral load was 100,000 copies/ml (range 3.6 to 6 log). Baseline median CD4 count was 421 (range 3-917). Enrollment included 66 males and 2 females: 63% caucasian, 28% Black, 3% Hispanic.

One hundred treatment-naÔve patients were randomized to receive one of three dosage levels of ABT-378/r (200/100 mg bid, 400/100 mg bid or 400/200 mg bid) together with d4T bid and 3TC bid given either from study entry (group 2) or after 3 weeks (group 1). Enrollment in group 2 began following an evaluation of preliminary efficacy and safety of ABT-378/r in group 1. After 48 weeks, all patients began conversion to open-label ABT-378/r 400/100 mg bid.

RESULTS

• On Treatment Analysis: 93% in group 1 (25/27) and 100% (57/57) in group 2 had VL <400 copies/ml at week 72
• Intent-to-treat analysis (M=F): 78% (25/32) in group 1 and 84% in group 2 (57/68) had VL <400 copies/ml at week 72
• On-treatment analysis of <50 copies/ml: 96% (26/27) in group 1 and 96% (54/56) in group 2 had <50 copies at week 72
• ITT analysis of <50 copies/ml: 81% (26/32) in group 1 and 79% (54/68) in group 2 had <50 copies/ml at week 72
• Patients with baseline VL >100,000, 87% (ITT) had <400 copies at week 48 (n=41)
• Patients with VL<100,000 copies/ml, 78% had <400 copies/ml
• Mean CD4 increases of 240 (group 2) to 304 (group 1) from baseline
• Authors reported adherence rate based on patient reported dose interruptions was 98% through 72 weeks. The most common adverse events were diarrhea, nausea, and abnormal stools. At 72 weeks, only one patient had discontinued due to an adverse event/lab abnormality related to study drug.

MOST COMMON ADVERSE EVENTS and LAB ABNORMALITIES

Adverse Events*

Grade 3/4 Lab Abnormalities

* adverse events of at least moderate severity and probable or unknown relationship to ABT-378/r are included
** >3 loose stools
***<3 loose stools

4- 4/8 patients with AST/ALT elevations were seropositive for HBV surface antigen (HbsAg) or hepatitis C antibody at baseline

PATIENT DISPOSITION at WEEK 72

Of the 100 patients enrolled 13 disconcontinued at or before week 72. One person discontinued due to AST/ALT elevations said to be drug related. 4 disct. Due to non-compliance. One person due to drug addiction. # others disct : lymphoma, hyperglycemia in diabetic patient, alcohol detox.