[25] MONITORING INTRACELLULAR HIV1 REPLICATION IN BLOOD AND LYMPHOID TISSUE IN ANTIRETROVIRAL NAIVE SUBJECTS RECEIVING AMPRENAVIR (APV), ABACAVIR (ABC), AND 3TC (COLA3003 STUDY)

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] MONITORING INTRACELLULAR HIV1 REPLICATION IN BLOOD AND LYMPHOID TISSUE IN ANTIRETROVIRAL NAIVE SUBJECTS RECEIVING AMPRENAVIR (APV), ABACAVIR (ABC), AND 3TC (COLA3003 STUDY)

[AUTHOR(S):] Patterson B, Becker S, Snidow J, Pobiner B, Landay A
Children's Memorial Hospital, Chicago, Illinois, USA

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 25

[ABSTRACT:]: We reported that persistent HIV-1 replication was found in CD4⁺, CD45RO+ T-lymphocytes in the peripheral blood (PBMCs) of subjects on HAART with undetectable plasma viral load (Lancet 343;211-212, 1999). Here, we quantified the persistently productive HIV-1 (HIV-1 gag-pol mRNA+) reservoirs in PBMCs and lymphoid tissue (LT) biopsies from subjects in an ongoing, prospective study. We analyzed samples from 5 subjects at baseline (BL), 24, and 48 weeks following therapy consisting of APV (1200 mg/BID), ABC (300 mg/BID), and 3TC (150 mg/BID). Simultaneous immunophenotyping/ultrasensitive fluorescence in situ hybridization (gag-pol mRNA+) was performed on PBMCs using flow cytometry and on tissue using laser confocal image analysis. Paired t-tests with p<0.05 were significant. After 48 weeks of therapy, 4 of 5 subjects had plasma HIV-1 RNA less than 50 copies/mL. HIV-1 gag-pol mRNA+, CD4⁺, CD45RO+ T-cells in peripheral blood decreased from 1.24% at BL to 0.16% (p=0.016) and 0.24% (p=0.027) at 24 and 48 weeks, respectively. The total of HIV-1 gag-pol mRNA+ cells in LT decreased from 2.02% at BL to 1.5% (NS) and 1.72% (NS) at 24 and 48 weeks, respectively. When infected cells in different cellular reservoirs are analyzed separately, HIV-1 gag-pol mRNA+, CD4⁺, CD45RO+ T-cells decreased from 1.73% to 0,22% (p=0.008) while the percentage of infected macrophages increased from 0.3% at BL to 0.7% (NS) and 1.5% (NS) at 24 and 48 weeks, respectively. This increase was driven by 1 subject with a shift of HIV-1 replication to the macrophage reservoir in LT at 24 weeks (3.2%) that increased by 48 weeks (6.8%). Increased in-cell replication at 24 weeks predated an increase of plasma viral load to 6253 copies/mL at 48 weeks. This regimen results in less persistent viral replication in peripheral blood. Macrophages may represent a relatively resistant cellular reservoir during HAART therapy necessitating cell-specific viral load monitoring and cell-specific antiretroviral therapy.

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