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/μl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n =14) or disease (HIV+CTB, n =17). Their lymphoproliferative and IFN-γ 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. [Copyright &y& Elsevier]