title: Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection.
abstract: Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals.
  
  
  
  CD4 count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 <350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0).
  
  
  
  Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later.
  
  
  
  Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.
authors.affiliation: *Department of Medicine, Imperial College, London, United Kingdom; †Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom; ‡Medical Research Council/Uganda Virus Research Institute Research Unit on AIDS, Entebbe, Uganda; §Kirby Institute University of New South Wales and Centre for Applied Medical Research, St Vincent's Hospital, Sydney, Australia; ‖HIV Prevention Unit, Medical Research Council, Durban, South Africa; ¶Projeto Praça Onze, Hospital Escola Sao Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; #Division of Infectious Diseases, Ospedale San Raffaele, Milan, Italy; **Department of HIV, Faculty of Medicine, Guys and St Thomas' NHS Trust/Kings College London, United Kingdom; and ††Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: John
authors.initials: J
authors.lastname: Thornhill
authors.forename: Jamie
authors.initials: J
authors.lastname: Inshaw
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.forename: Julie
authors.initials: J
authors.lastname: Fox
authors.forename: Miriam
authors.initials: M
authors.lastname: Samuel
authors.forename: Jose M
authors.initials: JM
authors.lastname: Miro
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male
chemical_list: D019380:Anti-HIV Agents