Sophie Novelli1, Camille Lécuroux2, Véronique Avettand-Fenoel3, Rémonie Seng4, Asma Essat1, Philippe Morlat5, Jean-Paul Viard6, Christine Rouzioux3, Laurence Meyer4, Cécile Goujard7. 1. National Institute of Health and Medical Research (INSERM), Centre for Research in Epidemiology and Population Health (CESP), Paris-Sud University, France. 2. Commissariat à l'énergie atomique et aux énergies alternatives (CEA) -Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases (IMVA), Infectious Disease Models and Innovative Therapie (IDMIT), Institut de biologie François Jacob (IBJF), Direction de la recherche fondamentale (DRF), Fontenay-aux-Roses, France. 3. Paris Descartes University, EA 7327, Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker Hospital, Virology Department, France. 4. INSERM, CESP, U1018, Paris-Sud University, AP-HP, Bicêtre Hospital, Department of Public Health and Epidemiology, Le Kremlin-Bicêtre, France. 5. Bordeaux University Hospital, Saint André Hospital, Department of Internal Medicine, France. 6. Paris Descartes University, EA 7327, Sorbonne Paris Cité, AP-HP, Hôtel Dieu Hospital, Unit of Therapeutics in Immunology and Infectiology, France. 7. INSERM, CESP, U1018, Paris-Sud University, AP-HP, Bicêtre Hospital, Department of Internal Medicine, Le Kremlin-Bicêtre, France.
Abstract
Background: We aimed to determine the consequences of delayed human immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI). Methods: We selected patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO cohort, treated for ≥36 months, with sustained HIV RNA <50 copies/mL: 77 treated within 1 month following PHI diagnosis (immediate ART) and 73 treated >12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. Results: The decrease of HIV DNA levels was more marked in the immediate than deferred ART group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82 months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio, ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term suppressive cART failed to normalize inflammation levels, which were not associated with immunovirological markers. Conclusions: Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.
Background: We aimed to determine the consequences of delayed human immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI). Methods: We selected patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO cohort, treated for ≥36 months, with sustained HIV RNA <50 copies/mL: 77 treated within 1 month following PHI diagnosis (immediate ART) and 73 treated >12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. Results: The decrease of HIV DNA levels was more marked in the immediate than deferred ART group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82 months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio, ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term suppressive cART failed to normalize inflammation levels, which were not associated with immunovirological markers. Conclusions: Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.
Authors: Mary Clare Masters; Karen M Krueger; Janna L Williams; Lindsay Morrison; Susan E Cohn Journal: Expert Rev Clin Pharmacol Date: 2019-12 Impact factor: 5.045
Authors: Fredrick H Omondi; Sandali Chandrarathna; Shariq Mujib; Chanson J Brumme; Steven W Jin; Hanwei Sudderuddin; Rachel L Miller; Asa Rahimi; Oliver Laeyendecker; Phil Bonner; Feng Yun Yue; Erika Benko; Colin M Kovacs; Mark A Brockman; Mario Ostrowski; Zabrina L Brumme Journal: J Virol Date: 2019-03-05 Impact factor: 5.103
Authors: Genevieve E Martin; Debattama R Sen; Matthew Pace; Nicola Robinson; Jodi Meyerowitz; Emily Adland; John P Thornhill; Mathew Jones; Ane Ogbe; Lucia Parolini; Natalia Olejniczak; Panagiota Zacharopoulou; Helen Brown; Christian B Willberg; Nneka Nwokolo; Julie Fox; Sarah Fidler; W Nicholas Haining; John Frater Journal: Front Immunol Date: 2021-06-04 Impact factor: 7.561