Background: ABT-378/r is a novel HIV protease inhibitor (PI) with mean pre-dose 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.

Methods: 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. Phenotype/genotype was performed on 56 baseline viral isolates.

Results: 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. At wk 24, VL was < 400 c/mL in 86% (43/50) of pts. on treatment (intent-to-treat missing = failure: 75%). VL was < 400 c/mL at wk 24 in 92% and 80% of pts on treatment with 533/133 mg BID and 400/100 mg BID, respectively (p=0.417). Mean CD4 increase from BL to wk 24 was 37 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. Seven patients have discontinued for virologic failure (n=3) or adverse events (n=4) to date.

Conclusion: Efficacy/safety evaluation at 24 weeks of the combination of ABT-378/r and EFV is encouraging in experienced patients.

Pacific Horizon Medical Group¹ ,C.H.U. Saint-Pierre-Brussels², Osp. S. Raffaele³, Med. Klinik Uni Bonn⁴, H. Rothschild⁵, H. de Beaumont⁶, Charite Humboldt-University Berlin⁷, Acadmic Med. Ctr. Amsterdam⁸, Aaron Diamond⁹, H. Pitie-Salpetriere¹⁰, U. Di Brescia¹¹, and Abbott Laboratories¹²

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