Enhanced Hiv-Specific Immune Responses In Chronically Hiv-Infected Patients Receiving Didanosine Plus Hydroxyurea

Background: The role of hydroxyurea (HU) in the treatment of HIV infection remains controversial. HU potentiates didanosine (ddl) antiviral activity and might exert immunomodulatory effects.Patients and methods: Immunologic parameters were examined in HIV-infected patients enrolled in a simplification trial in which ddl-HU was provided to subjects who had been on complete virus suppression under highly active antiretroviral therapy (HAART) for longer than 6 months. A total of 84 of these patients showed plasma viraemia repeatedly below 5000 HIV-RNA copies/ml, and were the main study population. A group of 22 patients who continued on HAART and another of 22 drug-naive HIV-positive individuals were taken as controls.Results: At 12 months, the levels of naive and memory T-cell subsets were similar in patients on ddl-HU and under HAART, whereas immune activation tended to be lower in the former group. The frequency of HIV-specific CD8+ T cells (CTL) directed against 125 peptides derived from Gag, Pol, Env, Nef and HIV regulatory proteins was similar among patients on ddl-HU and untreated controls, and significantly higher than in patients under HAART. This higher CTL response in patients on ddl-HU was seen even when considering only subjects with undetectable viral load. HIV-specific CD4+ T-cell responses were absent in almost all patients on HAART, whereas they were present in up to 19% of patients on ddl-HU.Conclusion: Treatment with ddl-HU provides higher levels of HIV-specific CD8+ and CD4+ T-cell responses than standard triple drug regimens. Thus, hydroxyurea might exert a beneficial immunomodulatory effect in HIV infection (C) 2004 Lippincott Williams Wilkins.