title: Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications.
abstract: HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Hôpital Necker Enfants-Malades, Laboratoire de Virologie, Paris, France veronique.avettand@nck.aphp.fr.
authors: Véronique
authors: V
authors: Avettand-Fènoël
authors: CHR d'Orléans, Service de Maladies Infectieuses et Tropicales, Orléans, France.
authors: Laurent
authors: L
authors: Hocqueloux
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre de Diagnostic et de Thérapeutique, Hôpital Hôtel Dieu, Paris, France.
authors: Jade
authors: J
authors: Ghosn
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Hôpital Bicêtre, Service de Médecine Interne, Paris, France.
authors: Antoine
authors: A
authors: Cheret
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Hôpital Necker Enfants-Malades, Laboratoire de Microbiologie Clinique, Paris, France APHP, Hôpital Necker Enfants-Malades, Unité d'Immunologie, Hématologie et Rhumatologie Pédiatriques, Paris, France.
authors: Pierre
authors: P
authors: Frange
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France.
authors: Adeline
authors: A
authors: Melard
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Centre de Diagnostic et de Thérapeutique, Hôpital Hôtel Dieu, Paris, France.
authors: Jean-Paul
authors: JP
authors: Viard
authors: Université Paris-Descartes, Sorbonne Paris-Cité, Faculté de Médecine, EA 7327, Paris, France APHP, Hôpital Necker Enfants-Malades, Laboratoire de Virologie, Paris, France.
authors: Christine
authors: C
authors: Rouzioux
mesh_terms: D015415:Biomarkers; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D019562:Viral Load; D017735:Virus Latency
chemical_list: D015415:Biomarkers; D004279:DNA, Viral