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

Abstract

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.

Fig. 1

Search strategy.

Fig. 2

Data synthesis: a process for collapsing and categorizing individual terms and definitions.

Fig. 3

Frequency of term usage by calendar period.

Fig. 4

Predominant components and common thresholds used in definitions of slow progression/viral control terms in HIV infection.

Fig. 5

Predominant components and common thresholds used in definitions of rapid progression/noncontroller terms in HIV infection.

Fig. 6

Relative characteristics of phenotypes referred to by different terms in the literature.