title: Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease.
abstract: We evaluated the anti-Mycobacterium tuberculosis (Mtb) immune responses of HIV patients after long-term successful HAART, presenting >500 TCD4+ cells/microl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n=14) or disease (HIV+CTB, n=17). Their lymphoproliferative and IFN-gamma responses were compared with those from HIV-uninfected controls either PPD+ (HIV-PPD+, n=17) or with past history of pulmonary tuberculosis (n=15). Most HIV-infected patients presented normal PHA responses while responses to the Mtb recombinant polypeptides ESAT-6 and Ag85B were markedly reduced. Responses to a whole Mtb lysate (S-Mtb) in HIV+PPD+ patients were lower than in HIV-PPD+ controls, while in HIV+CTB patients these responses were similar to that of past-tuberculosis controls. Comparison between the two HIV groups also suggested better S-Mtb responses in those cured from tuberculosis. Thus, while immune responses to single Mtb proteins are depressed even after successful HAART, reactivity to S-Mtb is high, specially in those cured from tuberculosis, possibly as a result of the survival of higher numbers of mycobacteria-specific T cell clones during the immunosuppression phase, which may afford sufficient protection against new Mtb challenges.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies (LIM-56), Medical School of the University of São Paulo, Av Dr Enéas de Carvalho Aguiar 500, 3rd floor, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Mendonça
authors.forename: Maury M
authors.initials: MM
authors.lastname: Tanji
authors.forename: Léia C R
authors.initials: LC
authors.lastname: Silva
authors.forename: Guilherme G
authors.initials: GG
authors.lastname: Silveira
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Alberto J S
authors.initials: AJ
authors.lastname: Duarte
authors.forename: Gil
authors.initials: G
authors.lastname: Benard
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology
chemical_list: D007371:Interferon-gamma