364   A Randomized Controlled Trial of Intermittent Versus Continuous HAART.

M. Dybul*¹, C. Yoder¹, M. Belson¹, B. Hidalgo¹, K. Hertogs², B. Larder², C. Hallahan¹, T. W. Chun¹, J. Justement¹, J. Metcalf¹, R. Davey¹, and A. S. Fauci¹.
¹NIAID/NIH, Bethesda, MD and²VIRCO, Belgium and UK.

Background:Continuous HAART, although effective in many patients, can be toxic and prohibitive in cost, and adherence is difficult. By decreasing the time that patients receive medications, intermittent HAART could reduce cost and toxicity while enhancing adherence.

Methods:70 HIV-infected individuals with plasma HIV RNA <500 copies/ml for >3 months and <50 copies/ml at screening and CD4⁺T cells >300 cells/mm³are being randomized to receive continuous HAART or cycles of 4 weeks off HAART followed by 8 weeks on HAART for 22 months.

Results:After 2—5 cycles, 13/14 of intermittent therapy patients have detectable plasma HIV RNA after each of the off-drug periods. 1 patient had plasma HIV RNA of 1233, 760 and <50 copies/ml at the end of 3 sequential off-drug cycles. 13/14 patients achieved <50 copies/ml during at least one on-drug period. 3/14 individuals failed to achieve <50 copies/ml (range -548) during at least 1 on-drug period. However, 3/10 patients receiving continuous HAART had plasma HIV RNA >50 copies/ml (range 86—1244) at matched times. 4 patients maintained >0.5 log reductions from the 1st to subsequent cycles off HAART, 2 maintained >0.5 log increases, 3 had no significant change and 5 had variable >0.5 log increases and decreases for a mean log difference of -0.5 and -0.1 for the 2nd and 3rd cycles, respectively. There was a decline in CD4⁺T cell counts of 17, 3 and 9% with the 1st, 2nd and 3rd cycles, respectively. However, when compared with the control group, only the 1st cycle decline was significant (p = 0.07). There was no significant change in CD8⁺T cell counts. Further follow-up and data on 39 patients will be presented. Genotype and phenotype drug susceptibility tests and data on HIV-specific immune responses will also be presented.

Conclusions:These data suggest that it may be possible to treat patients with repeated cycles of 1 month off and 2 months on HAART and achieve suppression of plasma HIV RNA and maintain CD4⁺T cell levels after the 2- months on-drug period. Intermittent HAART may be an effective long-term therapeutic approach to control plasma HIV RNA and maintain CD4⁺T cell counts while reducing cost and toxicity and enhancing adherence.