C Benson, S Brun, Y Xu, K Orth, S Deeks, H Kessler, R Murphy, D Wheeler, C Hicks, J Eron, J Feinberg, R Gulick, P Sax, R Stryker, S Riddler, M Thompson, M King, C Fields, A Potthoff, B Bernstein, A Hsu, R Bertz, A Molla, H Mo, D Kempf, E Sun and A Japour
ABSTRACT: Background: ABT-378 is a novel HIV protease inhibitor (PI) with excellent in vitro activity. ABT-368/r, stavudine and lamuvidine suppressed HIV RNA to <400 copies/mL in 93-95% of antiretroviral (ARV)-naïve patients in 24 weeks with no discontinuations for adverse events (AEs) related to study drug.
Objectives: (I) To examine the antiviral activity of ABT-378/r in patients with viral load (VL) rebound after receiving a triple drug regimen including an initial single PI. (ii) To determine the safety/antiviral activity of a regimen containing ABT-378/r, nevirapine and two NRTIs.
Methods: HIV-positive patients with VLs of 103-10 copies/ml while being treated with a PI and two NRTI s were included. Prior therapy with more than one PI or and NNRTI was not permitted. On day 1, patients were randomized to substitute blinded ABT-378/r, 400mg/100mg twice daily or 400 mg/200mg twice daily, for their original PI. On day 14, nevirapine was added, and the NRTIs were altered to include one or more new NRTI.
Results: Seventy patients were enrolled. Previous PI included indinavir (44%), nelfinavir (36%), saquinavir (13%), ritonavir (6%) and amprenavir (1%). Median baseline plasma HIVE RNA was 4.0 log10 copies/mL. Mean baseline CD4 cell count was 380 cells/mm3. During the initial 2 weeks, 66/70 patients (94%) had „0.5 log10 copies/ml decrease in HIV RNA (n=42) or a viral load value <400 copies/ml (n=24). Response during the first 2 weeks appeared to be independent of the previous PI. 56/64 patients (84%) had a decline in VL to <400 copies/ml at week 24. The regimen was well tolerated with six discontinuations prior to week 24, two of which were attributed to drug.
Conclusions: ABT-378/r is well tolerated and has antiretroviral activity among patients who experienced virological rebound following treatment with a single PI-based triple regimen.
