Variation in HIV-1 set-point viral load: Epidemiological analysis and an evolutionary hypothesis

^†Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London W2 1PG, United Kingdom;
^§Infectious Diseases Epidemiology Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom; and
^¶HIV Monitoring Foundation, Academic Medical Centre of the University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands

Communicated by Stanley Falkow, Stanford University, Stanford, CA, September 10, 2007 (received for review February 9, 2007)

Abstract

The natural course of HIV-1 infection is characterized by a high degree of heterogeneity in viral load, not just within patients over time, but also between patients, especially during the asymptomatic stage of infection. Asymptomatic, or set-point, viral load has been shown to correlate with both decreased time to AIDS and increased infectiousness. The aim of this study is to characterize the epidemiological impact of heterogeneity in set-point viral load. By analyzing two cohorts of untreated patients, we quantify the relationships between both viral load and infectiousness and the duration of the asymptomatic infectious period. We find that, because both the duration of infection and infectiousness determine the opportunities for the virus to be transmitted, this suggests a trade-off between these contributions to the overall transmission potential. Some public health implications of variation in set-point viral load are discussed. We observe that set-point viral loads are clustered around those that maximize the transmission potential, and this leads us to hypothesize that HIV-1 could have evolved to optimize its transmissibility, a form of adaptation to the human host population. We discuss how this evolutionary hypothesis can be tested, review the evidence available to date, and highlight directions for future research.

Footnotes

^‡To whom correspondence should be addressed at:
Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
E-mail: c.fraser{at}imperial.ac.uk
Author contributions: C.F., F.d.W., and W.P.H. designed research; C.F., T.D.H., and R.C. performed research; C.F. contributed new reagents/analytic tools; C.F., T.D.H., and R.C. analyzed data; and C.F., T.D.H., R.C., and W.P.H. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0708559104/DC1.
↵ ‖ Laeyendecker, O., Li, X., Arroyo, M., McCutchan, F., Gray, R., Wawer, M., Serwadda, D., Nalugoda, F., Kigozi, G., Quinn, T., et al. (2006) The Effect of HIV Subtype on Rapid Disease Progression in Rakai, Uganda, Abstract 44LB, 13th Conference on Retroviruses and Opportunistic Infections, February 5–8, 2006, Denver, CO, www.retroconference.org/2006, accessed April 27, 2007.
Freely available online through the PNAS open access option.