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 (ddI) antiviral activity and might exert immunomodulatory effects.


METHODS
Immunologic parameters were examined in HIV-infected patients enrolled in a simplification trial in which ddI-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 ddI-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 ddI-HU and untreated controls, and significantly higher than in patients under HAART. This higher CTL response in patients on ddI-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 ddI-HU.


CONCLUSIONS
Treatment with ddI-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.
López
Mariola
M
Service of Infectious Diseases, Hospital Carlos III. Madrid, Spain.
Benito
José M
JM
Lozano
Sara
S
Barreiro
Pablo
P
Martínez
Pilar
P
González-Lahoz
Juan
J
Soriano
Vincent
V
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016049:Didanosine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D019384:Nucleic Acid Synthesis Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D019562:Viral Load
D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D016049:Didanosine; D006918:Hydroxyurea