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Abstract
PERSISTENT DEPLETION OF CD4 + T CELLS IN LYMPHOID TISSUES AMONG PATIENTS RANDOMIZED TO TRIPLE NUCLEOSIDE VS. PROTEASE OR NONNUCLEOSIDE CONTAINING REGIMENS IN THE ATLANTIC STUDY
SCHACKER T, NGYUEN P, GATELL J, HORBAN A, BERZINS B, LANGE J, MURPHY R
Standard combinations of drugs for HIV therapy include 2 nucleoside analogues (NA) + 1 protease inhibitor (PI) or 2 NA + 1 non-nucleoside analogue (NNA) and recently regimens of 3 NA have been recommended. Efficacy trials often use peripheral CD4 and HIV RNA measurements as endpoints however the primary site of HIV replication and subsequent immune damage is in lymphoid tissue (LT). We studied LT from persons in the Atlantic Study, a trial of 3 NA vs. 2NA + 1 NNA, vs. 2NA + 1 PI to determine differences in histology and quantity and location of CD4 cell populations. Tissue was graded as either normal, follicular hyperplasia or hypoplasia or depletion (no evidence of secondary follicle formation). Antibodies to CD4 were used to identify quantity and location of CD4 cells in LT. 21 subjects were biopsied (6 inguinal, 15 tonsil) a median of 84 weeks after entry, 10 to 3 NA, 8 to 2NA + 1 NNA, and 3 to 2 NA + 1 PI. At biopsy, the median CD4 count and plasma HIV RNA were 548 cells/mm3 (range 291-957) and <50 copies/ml (range <50- 368) respectively with no differences in peripheral CD4 count or plasma HIV-1 RNA in patients grouped by location, site of biopsy, or treatment group. All 19 samples with sufficient tissue for analysis showed evidence of abnormality in follicle formation with 8 having hyperplasia and 11 having significant depletion (2 hypoplasia and 9 with no evidence of follicle formation). Most with hyperplasia (5) received 3NA. Quantity and distribution of CD4 T cells was abnormal in 20/20 evaluable tissues; 8 with modest and 12 with significant decreases in the CD4 cell population. Most (8/12) with significant depletion of CD4 cells were receiving 3 NA. Quantity of CD4 cells in LT was only correlated to CD4 count at the time of biopsy. These preliminary data suggest that despite significant improvement in traditional markers of efficacy, significant abnormalities persist in lymphoid tissues especially among patients receiving 3 NA.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
26
Suggested Citation
"SCHACKERT, et al.
PERSISTENT DEPLETION OF CD4 + T CELLS IN LYMPHOID TISSUES AMONG PATIENTS RANDOMIZED TO TRIPLE NUCLEOSIDE VS. PROTEASE OR NONNUCLEOSIDE CONTAINING REGIMENS IN THE ATLANTIC STUDY.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
26"
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