Immune restoration by combination of a cytostatic drug (hydroxyurea) and anti-HIV drugs (didanosine and indinavir)

Franco Lori, Heiko Jessen, Judy Lieberman, Mario Clerici, Carmine Tinelli, Julianna Lisziewicz

Research output: Contribution to journalArticlepeer-review


Cell activation is essential for HIV infection. CD4+ T lymphocyte activation allows virus replication and CD8+ T lymphocyte activation may contribute to pathogenesis. We combined hydroxyurea, a cytostatic drug that inhibits cell activation and proliferation, with two drugs that inhibit HIV (didanosine and indinavir), to block the 'cell activation-virus production- pathogenesis' cycle. HIV was strongly suppressed in treated patients, and the average CD4 count increased to 224/mm+. Compared with a matched group of patients who had declined antiretroviral treatment, treated patients had a significantly lower proportion of activated CD8+ T lymphocytes and a significantly higher number of naive CD8+ and CD4+ T lymphocytes. The proliferative responses to allogeneic and influenza virus antigens were increased in treated patients, and a defect in CD3-ζ expression, the signaling chain of the T cell receptor complex, was reversed. The use of a cytostatic drug was not detrimental to the immune system; on the contrary, the combination of antiviral and cytostatic treatment improved all of the immune parameters tested.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalAIDS Research and Human Retroviruses
Issue number7
Publication statusPublished - May 1 1999

ASJC Scopus subject areas

  • Immunology
  • Virology


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