Defining HIV-1 transmission clusters based on sequence data

Abstract

: Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1 transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarizing the most common methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.

Fig. 1

Flow chart showing results from the literature search and inclusion of articles considered in the review.

Fig. 2

Number of articles stratified by strategy of HIV-1 transmission cluster determination in relation to availability and number of analysed sequences during the study period.

Fig. 3

Comparison between phylogenetic cluster definitions employing a branch support criteria with or without different distance thresholds.