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Journal of Virology, November 2002, p. 10745-10755, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10745-10755.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Intrapatient Diversity and Its Correlation with Viral Setpoint in Human Immunodeficiency Virus Type 1 CRF02_A/G-IbNG Infection

Indu Mani,1 Peter Gilbert,2 Jean-Louis Sankalé,1 Geoffrey Eisen,1 Souleymane Mboup,3 and Phyllis J. Kanki1*

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts,1 Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington,2 Laboratoire de Bactériologie-Virologie, Université Cheikh Anta Diop, Dakar, Senegal3

Received 9 April 2002/ Accepted 22 July 2002

The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1|-|log10 copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

* Corresponding author. Present address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-1267. Fax: (617) 432-3575. E-mail: pkanki{at}hsph.harvard.edu.

Journal of Virology, November 2002, p. 10745-10755, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10745-10755.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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