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

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.

• Authors: Felipe García, Montserrat Plana, Mireia Arnedo, Gabriel M Ortiz, José M Miró, Lucia Lopalco, Franco Lori, Tomás Pumarola, Teresa Gallart, José M Gatell
• Journal: AIDS (London, England) (AIDS) Vol. 17 Issue 1 Pg. 43-51 (Jan 03 2003) ISSN: 0269-9370 [Print] England
• PMID: 12478068 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Nucleic Acid Synthesis Inhibitors
• Hydroxyurea

Topics

• Adult
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active (adverse effects)
• CD4 Lymphocyte Count
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• HIV Infections (drug therapy, immunology, virology)
• HIV-1 (drug effects, physiology)
• Humans
• Hydroxyurea (therapeutic use)
• Male
• Nucleic Acid Synthesis Inhibitors (therapeutic use)
• Viral Load
• Virus Replication (drug effects)