7th Conference - Abstract 532

ABT-378/Ritonavir (ABT-378/r) Suppresses HIV RNA to <400 Copies/ml in 84% of PI-Experienced Patients at 48 Weeks

S. DEEKS*¹, S. BRUN¹⁴, Y. XU¹⁴, K. REAL¹⁴, C. BENSON², H. KESSLER³, R. MURPHY⁴, D. WHEELER⁵, C. HICKS⁶, J. ERON⁷, J. FEINBERG⁸, R. GULICK⁹, P. SAX¹⁰, R. STRYKER¹¹, S. RIDDLER¹², M. THOMPSON¹³, M. KING¹⁴, A. POTTHOFF¹⁴, A. HSU¹⁴, R. BERTZ¹⁴, A. MOLLA¹⁴, H. MO¹⁴, D. KEMPF¹⁴, A. JAPOUR¹⁴, and E. SUN¹⁴ for the M97-765 Study Group. ¹Univ. of California, San Francisco; ²Univ. of Colorado; ³Rush; ⁴Northwestern; ⁵Inf. Dis. Physicians; ⁶Duke; ⁷Univ. of North Carolina; ⁸Univ. of Cincinnati; ⁹Cornell; ¹⁰Harvard; ¹¹Pacific Oaks Res.; ¹²Univ. of Pittsburgh; ¹³AIDS Res.. Consortium of Atlanta; and ¹⁴Abbott Labs

Background: ABT-378/r is a novel HIV protease inhibitor with a trough plasma concentration (C_min)/EC₅₀ ratio for wild type HIV averaging less than or greater than 30, providing a pharmacologic barrier to the emergence of viral resistance and a potential treatment for resistant virus. Currently available protease inhibitors exhibit modest C_min/EC₅₀ ratios, ranging from 1-4.
Methods: Single PI experienced/NNRTI naive pts. (n=70) with viral load (VL) 10³-10⁵ copies/mL on current therapy were randomized to a blinded ABT-378/r dose (400/100 vs. 400/200 mg BID) with nevirapine and two NRTIs (at least one new).
Results: Previous PI included IDV (44%), NFV (36%), SQV (13%), RTV (6%), and APV (1%). For baseline viral isolates with full PI phenotype data available (N=55), 64% had less than or greater than 4-fold loss in susceptibility to previous PI. Median baseline VL was 4.0 log₁₀ copies/mL. At wk 48, 49/58 (84%) pts. on treatment had VL < 400 copies/mL (ITT missing = failure: 70%). Of 11 patients with > 4-fold reduced susceptibility to ABT-378 at baseline, 7 had VL <400 copies/mL at week 48 and one had VL < 400 copies/mL at last visit on study. Mean increase from baseline in CD4 cells at wk. 48 was 125 cells/microliter. The most common drug-related adverse events of at least moderate severity were diarrhea, nausea, and asthenia. Both doses have been very well tolerated to date with only 3 discontinuations for adverse events related to ABT-378/r through 48 weeks.
Conclusion: ABT-378/r is well tolerated and exhibits durable antiretroviral effect in PI experienced patients through 48 weeks of treatment.

Key Words: ABT-378, clinical study, resistance