The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection

Gilbert Mchantaf; Antoine Cheret; Adeline Melard; Asma Essat; Elise Gardiennet; Rebecca Bauer; Caroline Charre; Vincent Meiffredy; Lionel Piroth; Cécile Goujard; Laurence Meyer; Véronique Avettand-Fenoel

doi:10.1016/j.jve.2023.100357

The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection

J Virus Erad. 2023 Dec 9;9(4):100357. doi: 10.1016/j.jve.2023.100357. eCollection 2023 Dec.

Authors

Gilbert Mchantaf^{1

2

3}, Antoine Cheret^{2

4}, Adeline Melard², Asma Essat^{5

6}, Elise Gardiennet², Rebecca Bauer⁷, Caroline Charre^{2

8}, Vincent Meiffredy⁷, Lionel Piroth⁹, Cécile Goujard^{5

10}, Laurence Meyer^{5

7

6}, Véronique Avettand-Fenoel^{1

2

3}

Affiliations

¹ CHU d'Orléans, Orléans, France.
² INSERM U1016, CNRS UMR8104, Université Paris Cité, Institut Cochin, Paris, France.
³ Université d'Orléans, Orléans, France.
⁴ Plateforme de Médecine Ambulatoire, CHU Guadeloupe, France.
⁵ Centre de Recherche en Epidémiologie et Santé des Populations (CESP), INSERM U1018, Université Paris Saclay, Le Kremlin-Bicêtre, France.
⁶ AP-HP, Service d'Epidémiologie et de Santé Publique, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁷ INSERM SC10-US19, Villejuif, France.
⁸ AP-HP, Laboratoire de Virologie, Hôpital Cochin, Paris, France.
⁹ Infectious Diseases Department, Dijon University Hospital, INSERM CIC 1432, Module Épidémiologie Clinique, Université de Bourgogne, Dijon, France.
¹⁰ AP-HP, Service de Médecine Interne et d'Immunologie Clinique, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.

Abstract

Background: Understanding factors affecting the size and the evolution of the HIV reservoir is essential for the development of curative strategies. This study aimed to assess the impact of antiretroviral therapy (ART) initiated during primary infection (PHI) vs chronic infection (CHI) on the levels and dynamics of integrated HIV-1 DNA, a biomarker of viral persistence.

Methods: Integrated and total HIV-1-DNA were measured in the blood of 92 patients treated during PHI (early group) and 41 during CHI (deferred group), at diagnosis, ART initiation, and 12-24 months on treatment.

Results: On ART, detectable (>1.78 log₁₀ copies/10⁶ PBMCs) integrated HIV-1 DNA levels were significantly lower in the early vs deferred group (2.99 log₁₀vs 3.29 log_10,p = 0.005). The proportion of undetectable integrated HIV-1 DNA tended to be higher in the early group vs deferred group (61 % vs 46 %; p = 0.133).

Conclusion: Treatment initiated at PHI limits the levels of integrated HIV-1 DNA in blood. However, initiating treatment at CHI does not allow reaching such low levels in most patients, probably because the stable proviruses at that stage are present in the less prone to elimination long-lived cells. Thus, early ART could provide an opportunity to preparing for functional cure and eradication strategies.

Keywords: Deferred treatment; Early ART; Integrated HIV-1 DNA; Reservoir decay; Total HIV-1 DNA.