Virologic and Immunologic Effect of Antiretroviral Therapy on HIV-1 in Gut-Associated Lymphoid Tissue

Abstract

Objectives:We evaluated virologic and immunologic responses to antiretroviral therapy in gut-associated lymphoid tissue (GALT) compared with those found in peripheral blood. Methods:Eight HIV-1-infected individuals were treated with three reverse transcriptase inhibitors and one protease inhibitor. Endoscopic biopsies were performed at baseline, and at months 1, 2, and 6. We measured the level of 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 HIV-1 mRNA in the GALT was below assay detection although it persisted in peripheral blood mononuclear cells in 4 study subjects. Although the percentage of CD4+ lymphocytes increased significantly in peripheral blood, only modest increases occurred in GALT. The percentage of activated CD8+ T cells decreased significantly in peripheral blood whereas only modest reductions occurred in GALT. Conclusions:Antiretroviral therapy effectively suppressed HIV-1 replication in GALT. The percentage of CD4+ T cells in peripheral blood uniformly increased in all study subjects, whereas it was more variable in the GALT. Address correspondence and reprint requests to Andrew Talal, Weill Medical College of Cornell University, 525 E. 68th Street, F-231, New York, NY 10021 U.S.A.; e-mail: [email protected] Presented in part at the 5th and 6th Conferences on Retroviruses and Opportunistic Infections [abstracts 518 and 328], Chicago, Illinois, U.S.A. A. H. Talal is currently affiliated with Weill Medical College of Cornell University, New York City, New York, U.S.A. Manuscript received June 13, 2000; accepted October 26, 2000. © 2001 Lippincott Williams & Wilkins, Inc.