ABT-378/ritonavir (ABT-378/r) in Antiretroviral Naive HIV+ Patients: 72 Weeks

R. GULICK*¹, M. KING¹¹, S. BRUN¹¹, K. REAL¹¹, R. MURPHY², C. HICKS³, J. ERON⁴, J. THOMMES⁵, M. THOMPSON⁶, C. WHITE⁷, C. BENSON⁸, M. ALBRECHT⁹, H. KESSLER¹⁰, A. HSU¹¹, R. BERTZ¹¹, D. KEMPF¹¹, E. SUN¹¹, and A. JAPOUR¹¹ for the M97-720 Study Group. ¹Cornell; ²Northwestern; ³Duke; ⁴Univ. of North Carolina; ⁵Pacific Oaks Res.; ⁶AIDS Res. Consortium of Atlanta; ⁷Baylor; ⁸Univ. of Colorado; ⁹Harvard; ¹⁰Rush; and ¹¹Abbott 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 at least 30, providing a pharmacologic barrier to the emergence of viral resistance. Currently available protease inhibitors exhibit modest C_min/EC₅₀ ratios, ranging from 1-4.
Methods: Two groups of antiretroviral naive patients received d4T/3TC with a randomly assigned, blinded ABT-378/r dose: 200/100 mg or 400/100 mg BID, n=32(Group I); 400/100 mg or 400/200 mg BID, n=68(Group II). After 48 weeks, patients in both groups began open-label 400/100 mg BID dosing.  
Results: Median baseline viral load (VL) and CD4 count were 5.0 log₁₀ copies/mL and 421 cells/microliter (Group I) and 4.9 log₁₀ copies/mL and 301 cells/microliter (Group II). Adherence rate based on patient-reported dose interruptions was 98% through 48 weeks.  At week 48, 83%-86% of patients on treatment had VL <50 copies/mL.  25/27 patients (93%) on treatment in Group I and 45/45 patients (100%) having reached Week 72 in Group II had VL <400 copies/mL at Week 72. Week 72 ultrasensitive results will be presented. The most common adverse events were diarrhea, nausea, asthenia, and headache. All doses have been well tolerated to date with only one discontinuation for adverse events related to ABT-378/r through 72 weeks.  
Conclusion: ABT-378/r exhibits durable antiretroviral effect through 72 weeks of treatment. Tolerability and BID dosing of the drug may promote adherence, leading to the observed durable virologic response.

Key Words: ABT-378, adherence, clinical study

© 7th Conference on Retroviruses and Opportunistic Infections,
Foundation for Retrovirology and Human Health