ABT-378 (Kaletra): 96 Week Update in Treatment-Naive

Connie Benson from the University of Colorado reported an update at 96 weeks for M97-720, a non-comparative ongoing randomized study of ABT-378 in treatment naÔve patients. One hundred patients (96 men, 4 women, mean age 35) were radomized to receive one of three doses of ABT-378 (200/100 mg bid, 400/100 mg bid, or 400/200 mg bid), together with d4T (40 mg bid) and 3TC (150 mg bid) given either after study entry (Group 1) or from study entry (Group 2). Enrollment into Group 2 began after an evaluation of preliminary efficacy and safety of ABT-378 in Group 1. After 48 weeks, all patients began conversion to open-label ABT-378/r 400/100 mg dosing. Plasma HIV-RNA was quantified using the Roche Amplicor (400 copies/ml) and the Roche Ultrasensitive assay (50 copies/ml).

BASELINE CHARACTERISTICS

Median viral load was 4.8 log  (63,000 copies/ml), and CD4 was 326. The 32 patients randomized to Group 1 receiving ABT-378 monotherapy for 2 weeks (200/100 or 400/100), and then d4T/3TC was added. In Group 2, 68 patients were randomized from day one to either 400/100 or 400/200 + d4T/3TC.

RESULTS

Patient Discontinuations

Fourteen of the 100 enrollees discontinued at or before week 96. Benson reported 2 patients discontinued for reasons related to study drugs: AST/ALT increase (moderate severity, possibly related to study drug, patient was HbsAg+ and HCV antibody+); Diarrhea. Other reasons for discontinuation were: adverse event/HIV related event 3 (lymphoma, hyperglycemia in diabetic patient, alcohol detoxification); personal reasons 1 (left the USA); non-compliance 4; lost to follow-up 3; other (drug addiction) 1.

Most Common Lab Abnormalities

Benson did not report elevations in cholesterol & triglycerides that were above normal but below the thresholds below (300 & 750).

Viral Load Suppression to <400 copies/ml at 96 Weeks (n=86)  

• ITT 83%

• OT  97%

Viral Load Suppression <50 copies/ml at week 96 (n=86)

• ITT 78%

• OT 92%

Viral Suppression When Baseline Viral Load >100,000 copies/ml

Response rates to <400 copies/ml by week 20 were similar whether a person had <100,000 or >100,000 copies/ml, but it took longer to get there for people with >100,000 copies/ml. Median time to first VL <50 copies was 113 days for the group with baseline VL <100,000 copies/ml and 140 days for the group with baseline VL >100,000 copies/ml (p<0.001). Of note, 12/43 (28%) of patients in the group with baseline VL >100,000 had their first VL measure <50 at week 36 or later. Compared to 1/51 (2%) of the group with baseline VL <100,000.

OT

• >100,000 copies/ml - 98% (40/42) had <400 copies/ml

• <100,000 copies/ml - 96%  (43/44) had <400 copies/ml

ITT

• >100,000 copies/ml (40/45) 88% had <400 copies/ml

• <100,000 copies/ml (43/55) 78% had <400 copies/ml

Under 50 copies/ml was not reported. Mean CD4 increase was 290 above baseline.

Abbott reported that of the 6/100 patients who did not achieve viral load <50 copies/ml, 4 discontinued prior to ultrasensitive testing (first measurement at week 16) and 2 had documented non-compliance.