Agathe Leon1, Ignacio Perez, Ezequiel Ruiz-Mateos, Jose Miguel Benito, Manuel Leal, Cecilio Lopez-Galindez, Norma Rallon, Jose Alcami, Jose Lopez-Aldeguer, Pompeyo Viciana, Carmen Rodriguez, Eulalia Grau, Jose Iribarren, Jose Maria Gatell, Felipe Garcia. 1. aHospital Clinic-Fundació Clinic, HIVACAT, Universidad de Barcelona, Barcelona bLaboratory of Immunovirology, Biomedicine Institute of Seville, Infectious Disease Unit, Virgen del Rocio University Hospital, University of Seville, Seville cIIS-Fundación Jiménez Diaz, UAM, Madrid dHospital Universitario rey Juan Carlos, Móstoles eCentro Nacional de Microbiología ISCIII fAIDS Immunopathology Laboratory, ISCIII, Madrid gHospital la Fe, Valencia hCentro Sanitario Sandoval, Madrid iHospital Trias i Pujol de Can Ruti, Badalona jHospital Donostia, San Sebastian, Spain. *Members of the EC and Immune Pathogenesis Working Group of the Spanish AIDS Research Network are listed in the Acknowledgements.
Abstract
BACKGROUND: The proportion of HIV controllers developing virologic, immunological or clinical progression and the baseline predictors of these outcomes have not been assessed in large cohorts. METHODS: A multicenter cohort of HIV controllers was followed from baseline (the first of the three HIV-1 RNA levels < 50 in elite controller or from 50 to 2000 copies/ml in viremic controllers) up to August 2011, to the development of a progression event (loss of viral load control, CD4 decline, AIDS or death) or to the censoring date (lost to follow-up or initiation of antiretroviral therapy). Predictive models of progression at baseline and a risk score for the combined HIV-1 progression end point were calculated. RESULTS: Four hundred and seventy-five HIV-1 controllers of whom 204 (42.9%) were elite controller with 2972 person-years of follow-up were identified. One hundred and forty-one (29.7%) patients lost viral load control. CD4 cell count declined in 229 (48.2%) patients. Thirteen patients developed an AIDS event and four died. Two hundred and eighty-seven (60.4%) developed a combined HIV-1 progression. Baseline predictors for the progression end points and for elite and viremic controller patients were very similar: risk for HIV-1 acquisition, baseline calendar year, CD4 nadir, viral load before baseline and hepatitis C virus coinfection. The probability of a combined HIV-1 progression at 5 years was 70% for elite controllers with the highest score compared with 13% for those with the lowest. CONCLUSION: HIV-1 disease progression in elite and viremic controllers is frequent. We propose a baseline clinical score to easily classify these patients according to risk of progression. This score could be instrumental for taking clinical decisions and performing pathogenic studies.
BACKGROUND: The proportion of HIV controllers developing virologic, immunological or clinical progression and the baseline predictors of these outcomes have not been assessed in large cohorts. METHODS: A multicenter cohort of HIV controllers was followed from baseline (the first of the three HIV-1 RNA levels < 50 in elite controller or from 50 to 2000 copies/ml in viremic controllers) up to August 2011, to the development of a progression event (loss of viral load control, CD4 decline, AIDS or death) or to the censoring date (lost to follow-up or initiation of antiretroviral therapy). Predictive models of progression at baseline and a risk score for the combined HIV-1 progression end point were calculated. RESULTS: Four hundred and seventy-five HIV-1 controllers of whom 204 (42.9%) were elite controller with 2972 person-years of follow-up were identified. One hundred and forty-one (29.7%) patients lost viral load control. CD4 cell count declined in 229 (48.2%) patients. Thirteen patients developed an AIDS event and four died. Two hundred and eighty-seven (60.4%) developed a combined HIV-1 progression. Baseline predictors for the progression end points and for elite and viremic controller patients were very similar: risk for HIV-1 acquisition, baseline calendar year, CD4 nadir, viral load before baseline and hepatitis C virus coinfection. The probability of a combined HIV-1 progression at 5 years was 70% for elite controllers with the highest score compared with 13% for those with the lowest. CONCLUSION:HIV-1 disease progression in elite and viremic controllers is frequent. We propose a baseline clinical score to easily classify these patients according to risk of progression. This score could be instrumental for taking clinical decisions and performing pathogenic studies.
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