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Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy

Macías, Juana; Japón, Miguel A.b; Leal, Manuelc; Sáez, Carmenb; Pineda, Juan A.a; Segura, Dolores I.b; Ortega, Joséd; Lissen, Eduardoc

Basic Science

Background: The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure.

Objective: To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts ≥ 500/μl.

Methods: From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts ≥ 500/μl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones.

Results: Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks.

Conclusion: This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

From the aServicio de Medicina Interna, Hospital Universitario Virgen de Valme, Ctra. Cádiz s/n, 41014 Seville, Spain; bDepartamento de Anatomía Patológica, cGrupo para el Estudio de la Hepatitis vírica y SIDA, and dServicio de Otorrinolaringología, Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, C/Manuel Siurot s/n, 41013 Seville, Spain.

Corresponding author: Juan Macías, C/Tabladilla, 1C 3°I, 41013 Seville, Spain. Tel: +34 5 4252525; fax: +34 5 5015777/34 5 5015747; e-mail: jmacias@cica.es

Received: 19 September 2000;

revised: 1 February 2001; accepted: 2 May 2001.

Sponsorship: This study was partly supported by a grant from Bristol-Myers-Squibb.

© 2001 Lippincott Williams & Wilkins, Inc.