A cytostatic drug improves control of HIV-1 replication during structured treatment interruptions: A randomized study

Felipe García, Montserrat Plana, Mireia Arnedo, Gabriel M. Ortiz, José M. Miró, Lucia Lopalco, Franco Lori, Tomás Pumarola, Teresa Gallart, José M. Gatell

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To study the effect of highly active antiretroviral therapy (HAART) with and without hydroxyurea (HU) on changes in plasma viral load (VL) set-point, and on HIV-1-specific responses, after five cycles of structured treatment interruptions (STI). Methods: A group of 20 patients taking HAART for chronic HIV infection with VL <20 copies/ml were randomized to continue HAART or HAART plus HU for 24 weeks followed by five STI cycles. HU was also stopped in cycles 1-3 but continued in cycles 4 and 5. The number of individuals maintaining a VL set-point <5000 copies/ml during the fifth interruption were determined. Results: VL remained <5000 copies/ml in eight out of nine patients in the HU group and in four out of ten patients in the HAART group after a median 48 weeks of follow-up after the fifth interruption (P=0.039). By STI cycle 5, there was a significant increase in the neutralizing activity (NA), in both magnitude and breadth of the total cytotoxic T lymphocyte (CTL) response and in lymphoproliferative response (LPR) from baseline. No significant differences were observed between HAART and HU groups in NA, CTL and LPR at any time-point. There were no differences in the NA titers at any time-point between responder and non-responder patients. There was a trend for higher CTL and LPR levels in responder patients (P=0.10). Conclusions: In this randomized, controlled study of STI with cycles of HAART or HAART plus HU, a lower peak VL rebound and a lower VL set-point was achieved in patients continuing HU while other drugs were discontinued. HU did not blunt anti-HIV-1-specific responses; however, control of VL did not correlate with anti-HIV-1-specific cellular immune responses.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalAIDS (London, England)
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 3 2003

Keywords

  • HIV-1 infection
  • Hydroxyurea
  • Structured therapy interruption

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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