An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration.
BACKGROUND
Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype.


METHODS
We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve).


RESULTS
Most definitions classify ∼ 1% as ECs with median HIV-RNA 43-903 copies/ml and median CD4>500 cells/mm(3). Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥ 92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up ≥ six months, or with 90% of measurements <400 copies/ml over ≥ 10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5-19.0 for non-ECs compared to ECs).


CONCLUSIONS
ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥ 10 years be used to define this phenotype.
Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom.
Ashley D
AD
Olson
Institut National de la Santé et de la Recherche Médicale U1018, Université Paris-Sud, le Kremlin-Bicêtre, France.
Laurence
L
Meyer
Amsterdam Public Health Service, Amsterdam, Netherlands.
Maria
M
Prins
Institut National de la Santé et de la Recherche Médicale U897, Université Bordeaux Segalen, Bordeaux, France.
Rodolphe
R
Thiebaut
Wellcome Trust Sanger Institute, Hinxton, United Kingdom ; University of Cambridge, Cambridge, United Kingdom.
Deepti
D
Gurdasani
Institut National de la Santé et de la Recherche Médicale U943, Paris, France ; Université Pierre et Marie Curie S943, Paris, France.
Marguerite
M
Guiguet
Université Paris Descartes, EA 3620, Hôpital Necker-Enfants Malades, Paris, France.
Marie-Laure
ML
Chaix
International AIDS Vaccine Initiative, San Francisco, California, United States of America.
Pauli
P
Amornkul
Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom.
Abdel
A
Babiker
Wellcome Trust Sanger Institute, Hinxton, United Kingdom ; University of Cambridge, Cambridge, United Kingdom.
Manjinder S
MS
Sandhu
Medical Research Council Clinical Trials Unit at University College London, London, United Kingdom.
Kholoud
K
Porter
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003299:Cooperative Behavior; D003710:Demography; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000235:genetics; D013997:Time Factors
D012367:RNA, Viral