AEGiS-15IAC: Enhanced HIV-specific immune responses in chronically HIV-infected patients receiving didanosine (ddI) plus hydroxyurea.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Enhanced HIV-specific immune responses in chronically HIV-infected patients receiving didanosine (ddI) plus hydroxyurea.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10270)

Lopez M, Soriano V, Lozano S, Ballesteros C, Barreiro P, Martinez P, Gonzalez-Lahoz J, Benito JM
Hospital carlos III, Madrid, Spain

BACKGROUND: The role of the cytostatic agent hydroxyurea (HU) in the treatment of HIV infection remains controversial. Previous studies have suggested that HU might exert immunomodulatory effects. The aim of this study was to analyze the impact of simplification therapy with didanosine (ddI) and HU on the levels of HIV-specific CD8 and CD4 T cell responses. Patients and

METHODS: 84 patients that initiated a simplification regimen with ddI-HU after a prolonged period of complete viral suppression with HAART, and maintained plasma viral load (VL) below 5000 copies/ml during 12 months, were selected. 22 patients that had continued on HAART for the same period of time and 22 patients naïve for antiretroviral treatment at the moment of the study were included as control groups. An IFN-a assay in response to 125 optimally-defined peptides from all HIV proteins was used to measure the level of HIV-specific CD8 T cells, and a standard lymphoproliferative assay in response to recall antigens and HIV antigens was employed to analyse CD4 T cell responses.

RESULTS: After 12 months of treatment the frequency of HIV-specific CD8 T cells against peptides derived from Gag, Pol, Env, Nef and Regulatory proteins were significantly increased in ddI-HU treated patients when compared to HAART-treated patients, and similar to those found in untreated patients. This increase was present even in those patients that maintained undetectable levels of VL. HIV-specific CD4 T cell responses were almost absent in patients treated with HAART, whereas they were present in up to 22% of ddI-HU treated patients.

CONCLUSIONS: Patients treated with an hydroxyurea-containing regimen show higher levels of HIV-specific CD8 and CD4 T cell responses than those treated with HAART. These data suggest that hydroxyurea has a beneficial immunomodulatory effect in HIV infection

Keywords: AEGIS, HIV, Didanosine, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Antiretroviral Therapy, Highly Active, HIV Infections, Hydroxyurea, Viral Load, Anti-HIV Agents, CD4-Positive T-Lymphocytes, T-Lymphocytes, Antigens, CD4, HIV Protease Inhibitors, Humans, immunology

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A10270