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A systematic review of definitions of extreme phenotypes of HIV control and progression

Gurdasani, Deeptia,b; Iles, Louisea,b; Dillon, David G.a,b; Young, Elizabeth H.a,b; Olson, Ashley D.c; Naranbhai, Vivekd,e; Fidler, Sarahf; Gkrania-Klotsas, Effrossynig; Post, Frank A.h; Kellam, Paula,i; Porter, Kholoudc; Sandhu, Manjinder S.a,b

doi: 10.1097/QAD.0000000000000049
Editorial Review

The study of individuals at opposite ends of the HIV clinical spectrum can provide invaluable insights into HIV biology. Heterogeneity in criteria used to define these individuals can introduce inconsistencies in results from research and make it difficult to identify biological mechanisms underlying these phenotypes. In this systematic review, we formally quantified the heterogeneity in definitions used for terms referring to extreme phenotypes in the literature, and identified common definitions and components used to describe these phenotypes. We assessed 714 definitions of HIV extreme phenotypes in 501 eligible studies published between 1 January 2000 and 15 March 2012, and identified substantial variation among these. This heterogeneity in definitions may represent important differences in biological endophenotypes and clinical progression profiles of individuals selected by these, suggesting the need for harmonized definitions. In this context, we were able to identify common components in existing definitions that may provide a framework for developing consensus definitions for these phenotypes in HIV infection.

aWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton

bStrangeways Research Laboratory, Department of Public Health and Primary Care, University of Cambridge, Wort's Causeway, Cambridge

cMedical Research Council, Clinical Trials Unit, Aviation House, London, UK

dCentre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

eWellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford

fImperial College Healthcare NHS Trust, London

gCambridge University Hospitals NHS Foundation Trust, Department of Infectious Diseases, Addenbrooke's Hospital, Cambridge

hKing's College London, Weston Education Centre

iDivision of Infection and Immunity, University College London, London, UK.

Correspondence to Deepti Gurdasani, MPhil, MD, Strangeways Research Laboratory, 2 Worts Causeway, Cambridge CB1 8RN, UK. E-mail:

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Received May 13, 2013

Accepted August 29, 2013

© 2014 Lippincott Williams & Wilkins, Inc.