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Hydroxyurea & STIs: A cytostatic drug improves control of HIV-1 replication
during structured treatment interruptions: a randomized study
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AIDS 2003; 17(1):43-51; Felipe Garcia
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.
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