Changes in tonsillar tissue in early HIV-1 infection and during 3 years ofantiretroviral therapy

Tonsillar tissue from individuals in the early stages of HIV-1 infection wa s studied during the natural course of infection and during antiretroviral therapy with and without a protease inhibitor in order to investigate marke rs of clinical progression and evaluate the effects of therapy. Tonsillar b iopsies and blood samples were collected at regular intervals during 3 year s and clinical observations were noted. Tonsillar morphology was evaluated and the fragmentation of the follicular dendritic cell network was quantifi ed by standardised follicular fragmentation rate (FR) analysis. Lymphocyte subsets were phenotyped by flow cytometry, and viral load was calculated by limiting dilution assay. The FRs were higher in the HIV-1-infected individ uals than in the uninfected controls, although tonsillar tissue from both g roups contained follicular fragmentation. During HIV-I infection, the FR in creased and the tonsillar CD4/CD8 ratio declined. During maximum viral supp ression, FR approached that of controls while tonsillar T cell subsets and blood CD4 cell counts normalised. Even when virus suppression was incomplet e, tonsillar improvements were observed in parallel with a resolution of th e HIV-l-related dermatological disorders. However, persistent viral replica tion paralleled distortion of the tonsillar architecture. We suggest that a normalisation of the lymphoid tissue may have important functional and cli nical implications in HIV-1 infection.