title: Immunoarchitecture of lymphoid tissue in HIV-infection during antiretroviral therapy correlates with viral persistence.
abstract: Plasma viral load and T-cell subset determinations in blood are the markers used for monitoring HIV-1 infection. However, key pathogenesis events, viral replication and most immunologic changes occur in the lymphoid tissues. We have studied the tonsillar biopsies of 30 patients in the early stages of the disease, before initiating treatment and after 12 and 36 months of fully effective highly active antiretroviral therapy. We have investigated the HIV RNA by polymerase chain reaction (lymphoid tissue viral load), the immunohistochemical HIV-p24 antigen expression, as well as the lymphoid tissue architecture and lymphoid cell subsets using morphometry. The lymphoid tissue viral load and the immunoexpression of p24, which was found to be mainly associated with follicular dendritic cells, decreased significantly after treatment, but did not disappear in all cases, even after 36 months of treatment. A significant improvement of the lymphoid tissue architecture was also observed after treatment, with recovery of follicular structures. These histological changes correlated with the lymphoid tissue viral load. Moreover, the counts of CD4+ increased whereas CD8+ and cytotoxic lymphocytes (CD8+ granzyme B+) decreased significantly, the latter in both interfollicular and intrafollicular areas. However, these cellular counts after treatment did not reach those of lymphoid tissue of non-HIV-infected patients used as control cases. Naive (CD45RA+) and memory (CD45RO+) cells also improved significantly after treatment. In conclusion, in HIV-infection the impact of treatment can only be assessed completely in the lymphoid tissue reservoir, where most of the virus is stored and associated with follicular dendritic cells. Highly active antiretroviral therapy produces a significant recovery of lymphoid tissue architecture and lymphoid cell subsets, which are associated with the decrease of lymphoid tissue viral load. However, these parameters studied in lymphoid tissue are not re-established completely, even after 36 months of highly active antiretroviral therapy.
authors.affiliation: Department of Pathology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain. lalos@clinic.ub.es
authors.forename: Llúcia
authors.initials: L
authors.lastname: Alòs
authors.forename: Pilar
authors.initials: P
authors.lastname: Navarrete
authors.forename: Vanesa
authors.initials: V
authors.lastname: Morente
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.forename: Marta
authors.initials: M
authors.lastname: Garrido
authors.forename: Montse
authors.initials: M
authors.lastname: Plana
authors.forename: Anna
authors.initials: A
authors.lastname: Mozos
authors.forename: Anna
authors.initials: A
authors.lastname: López
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil
authors.forename: Tomás
authors.initials: T
authors.lastname: Pumarola
authors.forename: Miguel
authors.initials: M
authors.lastname: Caballero
authors.forename: Jose L
authors.initials: JL
authors.lastname: Blanch
authors.forename: Emilio
authors.initials: E
authors.lastname: Fumero
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D024882:Drug Resistance, Viral; D005260:Female; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D016655:HIV Core Protein p24