Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infectionResearch in context
Pauline Trémeaux,
Tiphaine Lenfant,
Faroudy Boufassa,
Asma Essat,
Adeline Mélard,
Marine Gousset,
Olivier Delelis,
Jean-Paul Viard,
Marc Bary,
Cécile Goujard,
Christine Rouzioux,
Laurence Meyer,
Véronique Avettand-Fenoel
Affiliations
Pauline Trémeaux
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; AP-HP, Laboratoire de Virologie, Hôpital Cochin, Paris, France
Tiphaine Lenfant
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France
Faroudy Boufassa
Université Paris Sud, Université Paris Saclay, INSERM CESP U1018, le Kremlin-Bicêtre, France
Asma Essat
Université Paris Sud, Université Paris Saclay, INSERM CESP U1018, le Kremlin-Bicêtre, France; AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Adeline Mélard
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France
Marine Gousset
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France
Olivier Delelis
Laboratoire de Biologie et Pharmacologie Appliquée, Centre National de la Recherche Scientifique UMR8113, Cachan, France
Jean-Paul Viard
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; AP-HP, Centre de diagnostic et thérapeutique, Hôtel-Dieu, Paris, France
Marc Bary
AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Cécile Goujard
Université Paris Sud, Université Paris Saclay, INSERM CESP U1018, le Kremlin-Bicêtre, France; AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Christine Rouzioux
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France
Laurence Meyer
Université Paris Sud, Université Paris Saclay, INSERM CESP U1018, le Kremlin-Bicêtre, France; AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
Véronique Avettand-Fenoel
Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; AP-HP, Laboratoire de Microbiologie clinique, CHU Necker-Enfants Malades, Paris, France; Corresponding author at: Institut Cochin, Laboratoire de Microbiologie Clinique, CHU Necker Enfants Malades, 149, rue de Sèvres, 75743 Paris Cedex 15, France.
Background: In the current context of research on HIV reservoirs, offering new insights into the persistence of HIV DNA in infected cells, which prevents viral eradication, may aid in identifying cure strategies. This study aimed to describe the establishment of stable integrated forms among total HIV DNA during primary infection (PHI) and their dynamics during the natural history of infection. Methods: Total and integrated HIV DNA were quantified in blood from 74 PHI patients and 97 recent seroconverters (<12 months following infection, “progression cohort”). The evolution of both markers over six years was modelled (mixed-effect linear models). Their predictive values for disease progression were studied (Cox models). Findings: For most patients during PHI, stable integrated forms were a minority among total HIV DNA (median: 12%) and became predominant thereafter (median at AIDS stage: 100%). Both total and integrated HIV DNA increased over a six-year period. Patients from the progression cohort who reached clinical AIDS during follow-up (n = 34) exhibited higher total and integrated HIV DNA levels at seroconversion and a higher percentage of integrated forms than did slower progressors (n = 63) (median: 100% vs 44%). The integrated HIV DNA load was strongly associated with the risk of developing AIDS (aRR = 2.63, p = 0.002). Interpretation: The profile of “rapid” or “slower” progression in the natural history of HIV infection appears to be determined early in the course of HIV infection. The strong predominance of unstable unintegrated forms in PHI may explain the great benefit of this early treatment, which induces a sharp decrease in total HIV DNA. Fund: French National Agency for Research on AIDS and Viral Hepatitis. Keywords: Total HIV DNA, Integrated HIV DNA, Reservoirs, Natural history, Primary HIV infection, Acquired immunodeficiency syndrome, Kinetics
