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Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics: An Essential Tool Where the Burden is Greatest?

Dennis, Ann M. MD*; Herbeck, Joshua T. PhD; Brown, Andrew L. PhD; Kellam, Paul PhD§,‖; de Oliveira, Tulio PhD; Pillay, Deenan MBBS, PhD; Fraser, Christophe PhD#; Cohen, Myron S. MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1st, 2014 - Volume 67 - Issue 2 - p 181–195
doi: 10.1097/QAI.0000000000000271
Critical Review: Epidemiology and Prevention

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.

*Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC;

Department of Microbiology, University of Washington, Seattle, WA;

Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom;

§Wellcome Trust Sanger Institute, Cambridge, United Kingdom;

Division of Infection and Immunity, University College London, London, United Kingdom;

Wellcome Trust-Africa Centre for Health and Population Studies, University of Kwazula-Natal, ZA; and

#Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.

Correspondence to: Ann M. Dennis, MD, Division of Infectious Diseases, University of North Carolina at Chapel Hill, 130 Mason Farm Drive, Suite 2115, CB 7030, Chapel Hill, NC 27999-7030 (e-mail:

A.M.D. reports receiving support from the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through Grant KL2TR000084. J.T.H. reports receiving support from the University of Washington Center for AIDS Research, an NIH-funded program under award number P30AI027757, which is supported by the following NIH Institutes and Centers (NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA, NIGMS, NIDDK).

A.M.D. and J.T.H. contributed equally.

J.T.H reports receiving consulting fees from the Bill and Melinda Gates Foundation. All other authors have no conflicts of interest to disclose.

Received January 19, 2014

Accepted May 23, 2014

© 2014 by Lippincott Williams & Wilkins