Session 15Oral Abstract Presentations Treatment Strategies Session Day and Time: Wednesday 11:15 am - 12:45 pm Presentation Time: 12:30 Room: Auditorium
68lb A Randomized, Controlled Trial of Long Cycle Structured Intermittent Versus Continuous ARV Therapy for Chronic HIV Infection M Dybul*1, E Nies-Kraske2, M Daucher2, C Hallahan2, G Csako3, C Yoder4, L Ehler4, P Sklar4, M Belson4, B Hidalgo4, J Metcalf4, R Davey4, D Rock Kress4, A Fauci4 1NIAID,NIH, DHHS, Bethesda, MD; 2NIAID, NIH, DHHS, Bethesda, MD; 3WG Magnuson Clinical Center, NIH, Bethesda, MD; and 4NIAID, NIH, Bethesda, MD
Background: Although ARV therapy has significantly reduced mortality due to HIV infection it is associated with significant toxicities, adherence difficulties and a prohibitive cost. We have previously demonstrated that 7days on, 7 days off structured intermittent therapy (SIT) maintained suppression of plasma HIV RNA and preserved CD4+ T cell counts while reducing serum lipid levels. In this study we evaluated the effects of long cycle SIT on drug toxicity, virologic and immunologic parameters.
Methods: 52 patients with plasma HIV RNA < 50 c/ml and a CD4+ T cell count > 300 cells/mm3 were randomized to cycles of 4 weeks off followed by 8 weeks on or continuous therapy.
Results: Enrollment in the 70 patient study was terminated following the emergence of resistance to 3TC and/or EFV in 3 of 8 patients in the SIT arm receiving an EFV-based regimen. 1 patient receiving a PI-based regimen had new resistance to 3TC. 19 patients receiving SIT and 22 receiving continuous ARV therapy had samples for evaluation. There was no significant difference between arms in baseline (BL) or week 48 (end of 4th on-ARV period) levels of serum triglyceride, total and LDL cholesterol, ALT, AST and plasma hsCRP (p>0.05 for each comparison). There was a reduction at week 40 (end of 4th off-ARV period) in the SIT arm in only serum triglyceride (p=0.04) and total cholesterol (p=0.04). There was no difference in mean plasma HIV RNA level of the 1st to the 2nd (-0.33 log) and the 1st to the 4th (-0.46 log) cycle off ARV (p>0.5). There was no difference between arms in BL, week 40 and week 48 CD4+ and CD8+ T cell count and the percent of cells that were CD4+CD25+, CD8+CD25+, CD4+DR+ or CD4+ T cells that produced IFN-gamma in response to p24 Ag (p>0.05 for all comparisons). Patients who received SIT had a significantly higher percent of CD8+CD38+ and CD8+DR+ cells at week 40 and week 48 (p<0.01, p=0.002;p=0.04, p=0.02, respectively).
Conclusion: In contrast to short cycle SIT, long cycle SIT resulted in the emergence of resistance to EFV and 3TC and did not significantly reduce markers of toxicity at week 48. The periodic reductions in certain lipid levels during the off-ARV period may have clinical benefit; however, there was no reduction in hsCRP during the off-ARV period. There was no immunologic or virologic evidence for auto-immunization during 4 cycles of SIT. These results have significant implications for the design of long cycle SIT strategies.