Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection
Sophie Novelli,
Camille Lécuroux,
Cécile Goujard,
Jacques Reynes,
Agnès Villemant,
Laurent Blum,
Asma Essat,
Véronique Avettand-Fenoël,
Odile Launay,
Jean-Michel Molina,
Christine Bourgeois,
Laurence Meyer
Affiliations
Sophie Novelli
Université Paris-Saclay, UVSQ, Inserm, CESP, 94807 Villejuif, France
Camille Lécuroux
Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes, 92265 Fontenay-aux-Roses, France.
Cécile Goujard
Université Paris-Saclay, UVSQ, Inserm, CESP, 94807 Villejuif, France; Service de Médecine Interne et Immunologie clinique, Assistance Publique Hôpitaux de Paris (AP-HP), Hôpital de Bicêtre, Le Kremlin-Bicêtre, France
Jacques Reynes
Département des Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Montpellier, TransVIHMI, Inserm, IRD Université de Montpellier, Montpellier, France
Agnès Villemant
Service de Médecine Interne, AP-HP, Hôpital Beaujon, Clichy, France
Laurent Blum
Service de Médecine, Centre Hospitalier René Dubos, Pontoise, France
Asma Essat
Université Paris-Saclay, UVSQ, Inserm, CESP, 94807 Villejuif, France
Véronique Avettand-Fenoël
Institut Cochin – CNRS 8104, Inserm U1016, Université Paris Descartes, AP-HP, Laboratoire de Microbiologie clinique, Hôpital Necker-Enfants Malades, Paris, France
Odile Launay
Université de Paris, Faculté de Médecine, Inserm, CIC Cochin Pasteur, AP-HP, Hôpital Cochin, Paris, France
Jean-Michel Molina
Département de Maladies Infectieuses, AP-HP, Hôpital Saint-Louis, Inserm UMR 941, Université de Paris Diderot Paris 7, Sorbonne Paris Cité, Paris, France
Christine Bourgeois
Université Paris-Saclay, Inserm, CEA, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes, 92265 Fontenay-aux-Roses, France.
Laurence Meyer
Université Paris-Saclay, UVSQ, Inserm, CESP, 94807 Villejuif, France; Service de Santé Publique, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France; Corresponding author at: Inserm, CESP, Hôpital de Bicêtre, 82 rue du Général Leclerc – Secteur bleu Pierre Lasjaunias – Porte 89, 94276 Le Kremlin-Bicêtre, France.
Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours. Methods: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers. Findings: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis. Interpretation: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI. Funding: ANRS and Paris-Saclay University.
