Article (Scientific journals)
Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir.
DARCIS, Gilles; Bouchat, Sophie; Kula, Anna et al.
2017In AIDS, 31 (2), p. 181-189
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Keywords :
Adult; Female; HIV Infections/virology; HIV-1/growth & development; Humans; Leukocytes, Mononuclear/drug effects/virology; Male; Middle Aged; Virus Activation; Virus Latency/drug effects
Abstract :
[en] OBJECTIVE: HIV-1 reservoirs are the major hurdle to virus clearance in combination antiretroviral therapy (cART)-treated patients. An approach to eradicating HIV-1 involves reversing latency in cART-treated patients to make latent cells visible to the host immune system. Stimulation of patient cell cultures with latency-reversing agents (LRAs) ex vivo results in heterogeneous responses among HIV-infected patients. Determinants of this heterogeneity are unknown and consequently important to determine. DESIGN AND METHODS: Here, we grouped and retrospectively analyzed the data from our two recent HIV-1 reactivation studies to investigate the role of the HIV-1 reservoir size in the reactivation capacity by LRAs in ex vivo cultures of CD8-depleted peripheral blood mononuclear cells (PBMCs) isolated from 54 cART-treated patients and of resting CD4 T cells isolated from 30 cART-treated patients. RESULTS: Our results established a statistically relevant positive correlation between the HIV-1 reservoir size measured by total cell-associated HIV-1 DNA and the frequency of positive HIV-1 recovery measurements in response to various LRAs in ex vivo cultures of cells isolated from cART-treated HIV aviremic patients. HIV-1 reservoir size also correlated with the extracellular HIV-1 RNA median level measured in supernatants of cell cultures following LRA treatments. However, we identified HIV patients whose positive measurements frequency and median level of extracellular HIV-1 RNA deviated from linearity relative to their corresponding HIV reservoir size. CONCLUSION: We demonstrated that the reservoir size is one predictive marker of LRA effectiveness but this parameter alone is not sufficient. The identification of other predictive markers is necessary to predict the success of HIV anti-latency approaches.
Disciplines :
Immunology & infectious disease
Author, co-author :
DARCIS, Gilles ;  Centre Hospitalier Universitaire de Liège - CHU > Service des maladies infectieuses - médecine interne
Bouchat, Sophie
Kula, Anna
Van Driessche, Benoit
Delacourt, Nadege
Vanhulle, Caroline
Avettand-Fenoel, Veronique
De Wit, Stephane
Rohr, Olivier
Rouzioux, Christine
Van Lint, Carine
Language :
English
Title :
Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir.
Publication date :
2017
Journal title :
AIDS
ISSN :
0269-9370
eISSN :
1473-5571
Publisher :
Lippincott Williams & Wilkins, United States
Volume :
31
Issue :
2
Pages :
181-189
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 17 January 2018

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