Home Search Abstracts Browse Sessions Program Committee E-mail Abstract Author View Session

Session 13 Oral Abstracts
Antiretroviral Therapy: Emergence, Mechanisms, and Persistence of Resistance
Monday, 4 - 6:15 pm
Presentation Time: 5:15 pm
Room 3000


56
Randomized, Placebo-Controlled Trial of Abacavir Intensification in HIV-1-infected Adults with Plasma HIV RNA <500 Copies/mL
S Hammer*1, R Bassett2, M Fischl3, K Squires4, L Demeter5, J Currier6, G Morse7, V DeGruttola2, C Lalama2, S Snyder8, J Mellors9, ACTG 372A Study Team10, and Adult AIDS Clinical Trials Group
1Columbia Univ., New York, NY, USA; 2Harvard Sch. of Publ. Hlth., Boston, MA, USA; 3Univ. of Miami, FL, USA; 4Univ. of Southern California, Los Angeles, USA; 5Univ. of Rochester, NY, USA; 6Univ. of California, Los Angeles, USA; 7State Univ. of New York, Buffalo, NY; 8AACTG Operations Ctr., Rockville, MD, USA; 9Univ. of Pittsburgh, PA, USA; and 10NIAID-sponsored AACTG, Bethesda, MD, USA

Background:  Maximizing durability of viral suppression is an important goal of antiretroviral therapy. The objective of ACTG 372A was to determine if the intensification strategy of adding abacavir (ABC) to an effective indinavir (IDV)-dual NRTI regimen would delay virologic failure.

Methods:   ZDV-experienced subjects (n = 229) on therapy with IDV + ZDV (or d4T) + 3TC with HIV RNAs <500 copies/mL were randomized to add ABC 300 mg twice daily or placebo. The primary endpoint was time to treatment failure (a composite of confirmed virologic failure [2 consecutive HIV RNAs >200 copies/mL] and treatment discontinuation). Analysis was intent-to-treat using method of Kaplan-Meier. HIV RNA was measured by Roche Ultrasensitive method using 0.5 or 2.0 mL of plasma. Genotype at virologic failure was performed with the ABI ViroSeq assay.

Results:  Baseline characteristics:  88% men; median age 41; 64% white, 15% black, 17% Hispanic; median CD4 count 250/mL. Median follow-up was 4.4 years. 79% of subjects completed the trial and 54% remained on original Rx without differences between arms. The primary composite endpoint was reached in 61/116 (53%) of ABC vs 62/113 (55%) of placebo recipients (p = 0.77); virologic failure occurred in 34/116 (29%) of ABC vs 42/113 (37%) of placebo recipients (p = 0.22).  CD4 counts increased 180 cells/mL at week 240 without differences between arms. Rates of grade 3-4 signs/symptoms and lab abnormalities were comparable between arms. In secondary analyses:  rates of intermittent viremia (RNA >50 c/mL) were similar in both arms and not predictive of virologic failure;  modified Roche U/S RNA assay (detection limit = 6 copies/mL limit) in a subset of 100 subjects showed no differences in HIV RNA levels at weeks 2, 4, and 48; genotyping of failures showed comparable patterns of NRTI- and PI-associated mutations in both arms.

Conclusions:  In this ZDV-experienced population suppressed to <500 copies/mL on IDV + 2 NRTI, ABC intensification did not reduce the rate of treatment failure, virologic failure, frequency of intermittent viremia, or the level of residual viremia below 50 copies/mL. CD4 responses and resistance profiles at virologic failure were also not different. The strategy of intensification with ABC in patients virologically suppressed on a stable antiretroviral regimen cannot be recommended without additional clinical trial data.

Keywords: Intensification; Abacavir; Antiretroviral therapy