16   Antiretroviral Therapy (ART) Plus Cyclophosphamide (CTX) To Diminish HIV DNA in Lymphoid Tissue.

. J. A. Bartlett*¹, M. Silberman¹, G. D. Miralles², A. Sevin³, S. Pruitt¹, J. Ottinger¹, V. Gryszowka¹, S. Fiscus⁴, B. P. Bucy⁵, and the ACTG 380 Team.
¹Duke Univ. Med. Ctr., Durham, NC;²Trimeris Pharmaceuticals, Durham, NC;³Harvard Univ., Boston, MA;⁴Univ. of North Carolina, Chapel Hill; and⁵Univ. of Alabama at Birmingham.

Background:ART can decrease HIV RNA in peripheral blood and lymphoid tissue but HIV DNA does not decrease in either compartment.

Methods:ART (stavudine, lamivudine and nelfinavir) was initiated in 10 treatment-naïve subjects with CD4 cells >200/mm³. Subjects received ART until plasma HIV RNA <50 (step 1) and then were randomized to add CTX to ART (n = 5) or receive ART alone (n = 5) (step 2). CTX was given in escalating doses (750, 1200 and 1800 mg/m²IV). HIV DNA was measured in peripheral blood (PB) and lymphoid tissue (LT) using QC-PCR.

Results:Ten subjects entered with median plasma HIV RNA = 58,853 (6119—242,220) and median CD4 cells = 562 (195—1293). All ten subjects have completed steps 1 and 2. CTX was well tolerated and only one subject required dose modification. Median plasma HIV RNA levels remained <50 copies/ml through week 20 of step 2, although measurable RNA occurred more commonly in the ART + CTX group during step 2. HIV DNA in PB and LT declined in both groups over step 1. However, DNA did not decline further in either group over step 2.

Total lymphocyte counts and CD4⁺cells were lower in the CTX group during step 2, but CD4% did not decline.

Conclusions:ART + CTX in doses up to 1800 mg/m²does not diminish HIV DNA in PB or LT. Future studies may investigate more potent or specific cytoreduction in the context of fully suppressive ART.