8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001



Antiretroviral therapy (ART) plus cyclophosphamide (CTX) to diminish HIV DNA in lymphoid tissue

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:47 (abstract no. 16)

J. A. Bartlett1, 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; and 5Univ. 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.

PBMC LT
Step 1 Step 2 Step 1 Step 2
∈ DNA ∈ DNA ∈ DNA ∈ DNA
ART alone -1.27 +0.37 -0.73 -0.25
ART + CTX -0.48 -0.23 -0.91 +0.20
∈ DNA expressed as log10 coplies/1010 copies.

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.

2001-02-04
16

Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.