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Updated: Mar 28, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized
Christine Katlama1, Sidonie Lambert-Niclot, Lambert Assoumou
1aAP-HP, Hôpital Pitié-Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris bSorbonne Universités, UPMC Univ Paris 06 cINSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris dAP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris eORVACS, Hôpital Pitié-Salpêtrière, Paris fINSERM, UMR_S 1135, CIMI, Paris, France gSan Raffaele Scientific Institute, Milan, Italy hIrsi Caixa, Foundation. UAB, UVIC-UCC Hospital 'Germans Trias i Pujol', Badalona, Catalonia, Spain iRoyal Free and University College London Medical School, London, UK jCenter for Global Health and Department of Medicine, Northwestern University, Chicago, Illinois, USA kAP-HP, Hôpital Pitié-Salpêtrière, Service d'immunologie, Paris, France.
Background:
As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent.
Methods:
A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/μl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10. The primary endpoint was at least 0.5 log10 decrease in HIV-DNA in PBMC at W56. Secondary endpoints included ultrasensitive plasma viremia, immunologic changes and safety.
Results:
Twenty-nine patients were enrolled with median baseline 558 CD4 cell counts/μl, 360 HIV-DNA copies/10 PBMCs and 12 years on ART. No patient in either arm achieved the primary endpoint. Addition of IL-7 induced a significant expansion of CD4 T cells, primarily central-memory cells (+5%, P = 0.001) at week 12, together with an increase in levels of HIV-DNA/10 PBMC (+0.28 log10 copies/P = 0.001), and the proportion of patients with detectable ultrasensitive plasma HIV-RNA increased compared with week 8 (P = 0.07). At weeks 56 and 80, total and memory CD4 cell counts and total HIV-DNA/ml of blood remained elevated. In contrast, HIV-DNA/million PBMC and plasma viremia returned to baseline levels whereas activated HLA-DRCD4 T cells significantly decreased.
Conclusion:
IL-7 administration and dual ART intensification induced, despite a mild HIV reactivation, an amplification of the HIV reservoir, as a result of central-memory CD4 T-cell expansion, thus limiting this IL-7 based strategy.
Clinical Trial Registration:
This trial was registered with ClinicalTrials.gov, number NCT01019551.
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