Virologic and immunologic effect of antiretroviral therapy on HIV-1 in gut-associated lymphoid tissue

Objectives: We evaluated virologic and immunologic responses to antiretrovi ral therapy in gut-associated lymphoid tissue (GALT) compared with those fo und in peripheral blood. Methods: Eight HIV-1-infected individuals were treated with three reverse t ranscriptase inhibitors and one protease inhibitor. Endoscopic biopsies wer e performed at baseline, and at months 1, 2, and 6. We measured the level o f cell-associated multiply spliced and unspliced HIV-1 mRNA in GALT and in peripheral blood mononuclear cells. Immunologic responses were assessed by flow cytometry. Results: Levels of multiply spliced HIV-1 mRNA declined in parallel fashion both in peripheral blood and GALT. After 6 months of therapy, unspliced HI V-1 mRNA in the GALT was below assay detection although it persisted in per ipheral blood mononuclear cells in 4 study subjects. Although the percentag e of CD4(+) lymphocytes increased significantly in peripheral blood, only m odest increases occurred in GALT. The percentage of activated CD8(+) T cell s decreased significantly in peripheral blood whereas only modest reduction s occurred in GALT. Conclusions: Antiretroviral therapy effectively suppressed HIV-1 replicatio n in GALT. The percentage of CD4(+) T cells in peripheral blood uniformly i ncreased in all study subjects, whereas it was more variable in the GALT.