Phylogenetic studies of transmission dynamics in generalized HIV epidemics: an essential tool where the burden is greatest?

Abstract

Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics and suggest potential solutions.

Figure 1

Example population-level HIV phylogeny reconstructed from HIV pol sequences, to illustrate the basic approach to identifying traits associated with transmission using a phylogeny. Putative clusters of linked transmissions are identified using (ad-hoc) criteria such as pairwise genetic distance and/or nodal support (yellow boxes). Individual clinical or demographic traits are then examined for significant association with linked or unlinked individuals in the phylogeny (red lineages designate individuals with a certain trait, e.g. a particular transmission risk group). Note that not all individuals are included in transmission clusters, and that transmission clusters do not include all individuals with the “red” trait.

Figure 2

The regional distribution of HIV sequences deposited in the LANL HIV Sequence Database scaled to the estimated number of persons living with HIV, by WHO region and sub-Saharan Africa (inset). Map generated through query of the LANL database for number of sequences sampled by geographic region and country (http://www.hiv.lanl.gov; queried on June 26, 2013). Numbers were scaled to the 2011 WHO estimates on numbers of persons living with HIV by region and country (http://apps.who.int/gho/data/).