title: Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy.
abstract: OBJECTIVE
  We explored the impact of lifelong cumulative HIV viremia on immunological recovery during antiretroviral therapy, according to the timing of treatment initiation.
  
  
  METHODS
  We estimated lifelong cumulative HIV viremia in patients followed in the ANRS PRIMO cohort since primary infection, including 244 patients who started treatment during PHI and had at least one treatment interruption, and 218 patients who started treatment later but with no interruptions. The impact of cumulative viremia on current immunological status was analysed using linear and logistic regression models.
  
  
  RESULTS
  At the last visit on treatment, median CD4 cell count was 645 cells/μl in the early/intermittent treatment group (median time from infection 9.5 years, 4.8 years of continuous treatment since last resumption), and 654 cells/μl in the deferred/continuous treatment group (median time from infection 6.1 years, 3.0 years of continuous treatment). Only 36.1 and 39.8% of patients achieved a CD4/CD8 ratio of more than 1, respectively. Current CD4 cell count was not associated with cumulative HIV viremia in either group. In contrast, patients with high cumulative HIV viremia (>66th percentile vs. <33rd percentile) were less likely to achieve a CD4/CD8 ratio of more than 1 (26.8 vs. 43.3%, P = 0.003), even after controlling for the baseline CD4/CD8 ratio, treatment duration, sex and age. Much higher CD4 cell count and CD4/CD8 ratio were reached in early/continuous treatment, that is low viremia exposure group.
  
  
  CONCLUSIONS
  Our results underline the critical need in early-treated patients to maintain adherence, in order to limit cumulative HIV viremia and optimize immunological recovery, notably the CD4/CD8 ratio.
authors.affiliation: aCESP INSERM U1018, Epidemiology of HIV and STI bDepartment of Internal Medicine, AP-HP, Bicêtre Hospital, Le Kremlin-Bicêtre cDepartment of Infectious and Tropical Diseases, Croix-Rousse Hospital, Lyon dDepartment of Infectious and Tropical Diseases, Saint Louis Hospital, Paris eDepartment of Infectious Diseases, Perpignan Hospital, Perpignan fDepartment of Infectious Diseases, Bocage Hospital, Dijon and UMR1347, University of Burgundy gVirology Laboratory, AP-HP, Necker Hospital, Paris, France.
authors.forename: Rémonie
authors.initials: R
authors.lastname: Seng
authors.forename: Cécile
authors.initials: C
authors.lastname: Goujard
authors.forename: Evguenia
authors.initials: E
authors.lastname: Krastinova
authors.forename: Patrick
authors.initials: P
authors.lastname: Miailhes
authors.forename: Sylvie
authors.initials: S
authors.lastname: Orr
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Matthieu
authors.initials: M
authors.lastname: Saada
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D055118:Medication Adherence; D011446:Prospective Studies; D055502:Secondary Prevention; D013997:Time Factors; D014766:Viremia / Q000188:drug therapy*
chemical_list: D044966:Anti-Retroviral Agents