Complete immune and clinical recovery after highly active antiretroviral therapy in advanced vertically HIV-1 infected children

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the ability of long-term highly active antiretroviral therapy (HAART) to fully reconstitute the immune system in children with severe AIDS. PATIENT AND METHOD: Lymphoproliferative responses (LPR) were evaluated by incorporation of [H-3]-thymidine. Cytokine production in culture (IFN-gamma, IL-5) was quantified using commercially available specific ELISA assays. T-cells subsets were determined by 3-color flow cytometry and thymic production of T-cells was assessed by quantification of TCR rearrangement excision circles (TRECs). RESULTS: We present a vertically HIV-1-infected child at clinical category C, with long-standing CD4+ T-cells below 50/mul, who was monitored during 3-years after starting HAART by quantifying the viral load (VL), naive, memory, and activated T-cell subsets, and thymical function as well as clinical events. VL was suppressed to undetectable levels since the beginning of HAART with d4T, 3TC, nelfinavir, and efavirenz resulting in a dramatic immune reconstitution, achieving normal CD4+ T-cells counts after 6 months (25%, 597 CD4+ T-cells/mul) and perdurable undetectable VL levels. Naive CD4 and CD8 T-cells increased in parallel to TCR rearrangement excision circles (TRECs) levels, with a concomitant decrease in T-cell activation markers. Interestingly, the patient showed an increase in the lymphoproliferative responses to PHA; the IFN-gamma production by PBMCs increased with HAART while the production of IL-5 diminished, thus indicating a switch of type 2 to type 1 response. He recovered clinically and immunologically (up to normal levels) and remains asymptomatic at present. CONCLUSION: This report demonstrates that at least in these children, an immune and clinical recovery from an advanced stage of HIV-disease can be possible throught HAART.