Ruxandra Calin1, Chiraz Hamimi, Sidonie Lambert-Niclot, Guislaine Carcelain, Jonathan Bellet, Lambert Assoumou, Roland Tubiana, Vincent Calvez, Yasmine Dudoit, Dominique Costagliola, Brigitte Autran, Christine Katlama. 1. aAP-HP, Department of Infectious Diseases, Pitié-Salpêtrière University Hospital bSorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136) cDepartment of Immunology, Pitié-Salpêtrière Hospital, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CIMI, UMR_S 1135 dAP-HP, Virology Department, Pitié-Salpêtriêre University Hospital eORVACS, Paris, France. *Chiraz Hamimi and Sidonie Lambert-Niclot contributed equally to the writing of this article. †Details have been provided under Acknowledgements section. ‡Dominique Costagliola and Brigitte Autran contributed equally to the writing of this article.
Abstract
OBJECTIVES: To investigate the potential for combination antiretroviral therapy (cART)-free remission following analytic treatment interruption (ATI) in chronically HIV-infected patients with ultralow cell-associated DNA. METHODS: Pilot study of patients (pts) with plasma viral load (pVL) less than 50 copies/ml for more than 2 years on cART, CD4 above 500 cells/μl, CD4/CD8 above 0.9, CD4 nadir above 300 cells/μl and HIV-DNA below 100 copies/10 peripheral blood mononuclear cells (PBMCs), undergoing treatment interruption. Ultrasensitive pVL, CD4 cell count, triplicate HIV-DNA were measured at D0, W2, W4, and every 4 weeks off-ART until W48 and at W4, W12 and W24 after ART resumption (RxR). RxR occurred in case of pVL rebound above 400 copies/ml or CD4 above 400 cells or HIV-related clinical event. The primary endpoint was the percentage of patients who did not reach RxR criteria at W24. Individuals were to be enrolled in three cohorts of five. Enrolment in cohort 2 began if at least one of five patients from cohort 1 remained in success at W8. Cohort 3 did not start. RESULTS: Ten patients were enrolled, with median (range) CD4 1118 cells/μl (608-1494), CD4/CD8 2.1 (1.4-2.6), HIV-DNA 66 copies/10 PBMC (<66-66) at screening, viral suppression of 4.9 years (2.9-8.3), CD4 nadir 495 cells/μl (330-739). One patient remained off-ART up to W48. Viral rebound occurred in nine of 10 patients at W2 (2 patients), W4 (6 patients) and W12 (one patient). pVL was resuppressed on cART at W4 (8 patients) and W12 (one patient). HIV DNA returned to baseline values within a median of 12 weeks following RxR. CONCLUSION: In a highly selected population of 10 patients with chronic HIV infection, an excellent immune status, durable virological suppression and ultralow reservoir, the success rate of ATI was 10% (95% confidence interval 0.3-44.5%) and nine of 10 patients had prompt rebound of plasma viremia. Resumption of ART led to return to baseline cell-associated total DNA.
OBJECTIVES: To investigate the potential for combination antiretroviral therapy (cART)-free remission following analytic treatment interruption (ATI) in chronically HIV-infectedpatients with ultralow cell-associated DNA. METHODS: Pilot study of patients (pts) with plasma viral load (pVL) less than 50 copies/ml for more than 2 years on cART, CD4 above 500 cells/μl, CD4/CD8 above 0.9, CD4 nadir above 300 cells/μl and HIV-DNA below 100 copies/10 peripheral blood mononuclear cells (PBMCs), undergoing treatment interruption. Ultrasensitive pVL, CD4 cell count, triplicate HIV-DNA were measured at D0, W2, W4, and every 4 weeks off-ART until W48 and at W4, W12 and W24 after ART resumption (RxR). RxR occurred in case of pVL rebound above 400 copies/ml or CD4 above 400 cells or HIV-related clinical event. The primary endpoint was the percentage of patients who did not reach RxR criteria at W24. Individuals were to be enrolled in three cohorts of five. Enrolment in cohort 2 began if at least one of five patients from cohort 1 remained in success at W8. Cohort 3 did not start. RESULTS: Ten patients were enrolled, with median (range) CD4 1118 cells/μl (608-1494), CD4/CD8 2.1 (1.4-2.6), HIV-DNA 66 copies/10 PBMC (<66-66) at screening, viral suppression of 4.9 years (2.9-8.3), CD4 nadir 495 cells/μl (330-739). One patient remained off-ART up to W48. Viral rebound occurred in nine of 10 patients at W2 (2 patients), W4 (6 patients) and W12 (one patient). pVL was resuppressed on cART at W4 (8 patients) and W12 (one patient). HIV DNA returned to baseline values within a median of 12 weeks following RxR. CONCLUSION: In a highly selected population of 10 patients with chronic HIV infection, an excellent immune status, durable virological suppression and ultralow reservoir, the success rate of ATI was 10% (95% confidence interval 0.3-44.5%) and nine of 10 patients had prompt rebound of plasma viremia. Resumption of ART led to return to baseline cell-associated total DNA.
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