ABT-378/r is a novel HIV protease inhibitor (PI) with mean trough concentrations that exceed its serum adjusted EC₅₀ for wild type HIV by more than 75-fold when dosed at 400/100 mg BID. This increased inhibitory quotient should provide a pharmacologic barrier to the emergence of viral resistance, which is critical given variable patient adherence patterns.

100 ARV-naïve patients were enrolled and received ABT-378/r, d4T and 3TC. 32 patients (Group I) were randomized to either 200/100 mg or 400/100 mg BID ABT-378/r and 68 patients (Group II) were randomized to either 400/100 mg or 400/200 mg BID ABT-378/r. After 48 weeks, patients in both groups began open-label 400/100 mg BID dosing. Safety and efficacy data are provided through 108 weeks of follow up. Kaplan-Meier analysis was performed, for which loss of response was defined as confirmed viral load (VL) ³ 400 copies/mL following any value < 400 copies/mL. VL analysis using an assay with LOQ at 3 copies/mL was performed at selected timepoints.

Median baseline (BL) VL and CD4 count were 4.9 log₁₀ copies/mL and 334 cells/m L. Of 78 patients who have reached week 108, 76 (97%) had VL <400 copies/mL. The Kaplan Meier estimate of the proportion of patients still responding to ABT-378/r at week 108 is 83%. Subjects with baseline VL < 100,000 copies/mL were more likely to attain VL <3 copies/mL than those with baseline VL ³ 100,000 copies/mL (72% vs 37%, p = 0.001). Mean increase from baseline in CD4 cells at week 108 was 297 cells/m L overall. The most common adverse events were diarrhea, nausea, asthenia, and headache. All doses have been well tolerated to date with 3 patients discontinuing for adverse events related to ABT-378/r through 108 weeks.

ABT-378/r + d4T + 3TC exhibits durable antiviral activity beyond two years of treatment in treatment-naïve HIV-infected patients.