title: CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study.
abstract: BACKGROUND
  In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defining events and death.
  
  
  METHODS
  We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death.
  
  
  RESULTS
  We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45.
  
  
  CONCLUSIONS
  Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.
  
  
  BACKGROUND
  AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.
authors.affiliation: Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: cristina.mussini@unimore.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lorenzini
authors.affiliation: Department of Infection and Population, Health Division of Population Health, University College London, London, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: Clinic of Infectious Diseases, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
authors.affiliation: National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastri
authors.affiliation: Clinic of Infectious Diseases, Catholic University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Cingolani
authors.affiliation: Department of Public Health and Infectious Disease, Sapienza University of Rome, Polo Pontino, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lichtner
authors.affiliation: National Institute for Infectious Diseases, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
authors.affiliation: Clinic of Infectious Diseases, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents