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SHARE THIS ABSTRACT WITH A COLLEAGUE ABT-378/r is a novel HIV protease inhibitor (PI) with mean trough concentrations that exceed its protein binding corrected EC50 for wild type HIV by more than 75-fold when dosed at 400/100 mg BID. This increased inhibitory quotient (IQ) should provide antiviral activity in patients who have developed resistance to other PIs. Multiple PI experienced/NNRTI naive patients (n=57) with viral load (VL) >1000 c/mL on therapy were randomized to ABT-378/r at either 400/100 (3 capsules) or 533/133 mg (4 capsules) BID with EFV 600 mg QD and NRTIs. Thirty-five percent of patients received at least one new NRTI in conjunction with ABT-378/r and EFV. After 24 weeks, all patients began open label 533/133 mg BID dosing. Phenotype/genotype was performed on 56 baseline viral isolates. Median baseline (BL) viral load was 4.5 log10 copies/mL. The median number of prior PIs was 3. Sixty-eight percent of baseline viruses demonstrated > 4-fold loss in susceptibility to >3 licensed PIs. Mean susceptibility to ABT-378 at BL was 16-fold over wild type. VL was < 400 c/mL at wk 40 in 72% of patients for the Intent-to-treat Missing=Failure analysis (On-treatment: 87%). 10/11 (91%) of patients on treatment having reached week 48 to date had VL < 400 c/mL. Mean CD4 increase from BL to wk 40 was 62 cells/mL overall. The most common drug-related adverse events of at least moderate severity were diarrhea and asthenia. Lipid elevations were the most common laboratory abnormality. Four patients have discontinued for virologic failure and another 5 patients have discontinued for adverse events to date (3 study drug-related). The safety and efficacy of ABT-378/r and efavirenz plus NRTIs is encouraging in patients with extensive PI experience.
Abstract: ABT-378/Ritonavir
(ABT-378/r) and Efavirenz: © 2000 Medical Advocates for Social Justice |
