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242 Viral Rebound after Immunotherapy by HIV Lipopeptides and HAART Interruption in Patients Chronically Infected by HIV
D. Salmon*1, G. Pialoux2, H. Gahery1, N. Daniel1, A. Krivine1, T. Tuyen2, D. Sicard1, W. Rozenbaum2, and J. G. Guillet1
1Cochin Hosp. and 2Rothschild Hosp., Paris, France
Background: HIV lipopeptides have been shown to induce HIV cellular responses in a majority of non-HIV-infected volunteers (VAC04 Trial) and could be selected for specific immunotherapy in chronically infected patients controlled by HAART
Methods: In an open pilot trial, HIV chronically infected patients treated by HAART with undectectable HIV-RNA and a CD4 cell count >350/mm3 were immunized by 6 HIV lipopeptides (3 NEF, 2 GAG, and 1 ENV) in mixed micelles. Three injections were performed 3 weeks apart followed by HAART interruption after week 24. Cellular CD4+ and CD8+ immune responses and viral dynamics after HAART interruption were measured. Retreatment was decided in case of 2 HIV-RNA (VL) measures above 30,000 cop/mL after 1 month of HAART interruption.
Results: The 24 volunteers included had a median age of 39 years, a median baseline CD4 count of 644/mm and were treated by HAART for a median of 4 years (2-9). After immunization and HAART interruption, a rebound VL of was observed after a median delay of 2 weeks with by a peak of viral load at 3 weeks, followed then by a lower plateau. Treatment was restarted in 15 patients (group 1) but 9 patients controlled spontaneously their VL for more than 2 months (group 2). Anti-HIV proliferative responses at baseline were present in 5 patients of group 1 versus 2 patients of group 2. The volunteers in group 1 had a lower maximal HIV VL before HAART and a higher nadir of CD4 count than in group 2 (330 versus 226/mm3, p < 0.05). Although VL was undetectable in all patients for more than 1 year before immunization, resistant strains were detected at the time of viral rebound in 5 patients, all of them belonging to group 2. After the initial treatment was restarted, none of these patients reached an undetectable VL and modifications were necessary.
Conclusions: Despite a viral rebound observed in all patients after lipopeptides immunization followed by HAART interruption, some patients were able to control their viral replication for a few months. The correlation between viral control and immune responses is underway. One must be cautious with HAART interruption in such patients, since resistant strains may emerge at the time of viral rebound what might be in favor of a low grade replication despite undectable viral load or of conserved mutations in proviral DNA.
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