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.
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/106 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.
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/106 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.
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.
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.
Correspondence to Ruxandra Calin, MD, PhD, AP-HP, Department of Infectious Diseases, Pitié-Salpêtrière University Hospital, 47-85 Bd de l’Hôpital, 75013, Paris, France. Tel: +33 1 42 16 01 42; fax: +33 1 42 16 01 24; e-mail: firstname.lastname@example.org
Received 13 October, 2015
Revised 16 November, 2015
Accepted 16 November, 2015