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.
RCT Entities:
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: Emiliano Mancini; Filippo Castiglione; Massimo Bernaschi; Andrea de Luca; Peter M A Sloot Journal: PLoS One Date: 2012-04-27 Impact factor: 3.240
Authors: Csaba Fehér; Lorna Leal; Montserrat Plana; Nuria Climent; Alberto Crespo Guardo; Esteban Martínez; Pedro Castro; Vicens Díaz-Brito; Beatriz Mothe; Juan Carlos López Bernaldo De Quirós; Josep María Gatell; Patrick Aloy; Felipe García Journal: Open Forum Infect Dis Date: 2019-11-03 Impact factor: 3.835
Authors: Hartmut M Hanauske-Abel; Deepti Saxena; Paul E Palumbo; Axel-Rainer Hanauske; Augusto D Luchessi; Tavane D Cambiaghi; Mainul Hoque; Michael Spino; Darlene D'Alliessi Gandolfi; Debra S Heller; Sukhwinder Singh; Myung Hee Park; Bernadette M Cracchiolo; Fernando Tricta; John Connelly; Anthony M Popowicz; Richard A Cone; Bart Holland; Tsafi Pe'ery; Michael B Mathews Journal: PLoS One Date: 2013-09-23 Impact factor: 3.240