HAART in HIV-infected patients: restoration of antigen-specific CD4 T-cellresponses in vitro is correlated with CD4 memory T-cell reconstitution, whereas improvement in delayed type hypersensitivity is related to a decreasein viraemia

Objective: To analyse prospectively the effect of highly active antiretrovi ral treatment (HAART) on CD4 T-cell responses in vitro and in vivo in HIV-i nfected patients. Design: Prospective study with 49 protease inhibitor-naive adult patients. Data were collected at baseline and after 3 and 6 months of HAART. Methods: In vitro CD4 T-cell reactivity was analysed by stimulation of peri pheral blood mononuclear cells with several antigens. In vivo CD4 T-cell re activity (delayed type hypersensitivity) was assessed by Multitest Merieux. Both measurements were correlated to CD4 (memory) T-cell count and HIV-1 v iraemia. Results: Restoration of specific CD4 T-cell proliferation was observed in m ost patients. The in vitro T-cell response was restored more frequently aga inst antigens to which the immune system is constantly exposed (Candida alb icans, Mycobacterium tuberculosis, M. avium) as compared with a low-exposur e antigen (tetanus toroid). Overall, delayed type hypersensitivity detectio n rate increased under HAART. Multivariate analysis showed improvement of a ntigen-specific T-cell proliferation to be significantly associated with an increase in memory CD4 T-cells, whereas improvement of the delayed type hy persensitivity response was associated with a decrease in plasma HIV-1 RNA. Conclusions: HAART for 6 months restored antigen-specific CD4 T-cell respon se to several antigens. In vitro immune reconstitution was closely correlat ed with an increase in memory CD4 cells. Restoration of delayed type hypers ensitivity was associated with suppression of viraemia. It appears that in addition to expansion of memory CD4 cells, suppression of viraemia followin g HAART may allow an improved inflammatory reaction, thus providing even st ronger immune reconstitution. (C) 1999 Lippincott Williams & Wilkins.