title: Characterisation of long-term non-progression of HIV-1 infection after seroconversion: a cohort study.
abstract: BACKGROUND
  Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status.
  
  
  METHODS
  For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defined non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per μL or higher. We defined LTNP as non-progression during the first 10 years after seroconversion. We used longitudinal methods to characterise LTNP.
  
  
  RESULTS
  Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2·07 years (95% CI 1·96-2·17), giving estimated progression-free survivals of 18·4% (17·2-19·6) 5 years, 4·0% (3·6-4·5) 10 years, and 1·4% (0·9-1·5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0·28 [95%CI 0·26-0·31] per person-year at 10 years after seroconversion, 0·24 [0·19-0·29] per person-year at 15 years, and 0·18 [0·10-0·33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2·49 years [2·05-2·92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p < 0·0001) and HIV RNA load at 10 years after seroconversion (p = 0·005), but not age (p = 0·544), mode of infection (p = 0·621), sex (p = 0·676), or calendar year of seroconversion (p = 0·397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p < 0·0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p = 0·009).
  
  
  CONCLUSIONS
  Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually.
  
  
  BACKGROUND
  European Union Seventh Framework Programme.
authors.affiliation: Public Health Service Amsterdam, Amsterdam, Netherlands. Electronic address: jvdhelm@ggd.amsterdam.nl.
authors.forename: Jannie J
authors.initials: JJ
authors.lastname: van der Helm
authors.affiliation: Public Health Service Amsterdam, Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Geskus
authors.affiliation: Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Lodi
authors.affiliation: Service d'Epidémiologie et de Santé Publique, Hôpital de Bicêtre, AP-HP; INSERM U1018; Université Paris-Sud, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Robert Koch Institute, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gunsenheimer-Bartmeyer
authors.affiliation: Department of Infectious Diseases and Tropical Medicine, Università degli Strudi di Milano H S Paolo, Milan, Italy.
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.affiliation: MRC Clinical Trials Unit, University College London, London, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Greece.
authors.forename: Giota
authors.initials: G
authors.lastname: Touloumi
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.affiliation: MRC Clinical Trials Unit, University College London, London, UK.
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.affiliation: Public Health Service Amsterdam, Amsterdam, Netherlands; Department of Infectious Diseases, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Prins