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Journal of Virology, August 2005, p. 9799-9809, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9799-9809.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status

Sharon T. Sullivan,1 Usha Mandava,1 Tammy Evans-Strickfaden,1 Jeffrey L. Lennox,2 Tedd V. Ellerbrock,3 and Clyde E. Hart1*

HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,1 Grady Infectious Disease Program, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322,2 HIV Care and Treatment, Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia 303333

Received 21 October 2004/ Accepted 26 April 2005

Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P = 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4+ cell levels (VS, P = 0.05; BP, P = 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4+ cell levels decreased to low levels (<50 cells/µl). Quasispecies changes over time were associated with fluctuations in CD4+ cell levels; concordant increases or decreases in VS and BP divergence had greater CD4+ cell level changes than intervals with discordant changes (P = 0.05), and women with evolving quasispecies had greater decreases in CD4+ cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4+ cell levels.


* Corresponding author. Mailing address: Centers for Disease Control and Prevention, 1600 Clifton Road, NE Mailstop G19, Atlanta, GA 30333. Phone: (404) 639-1032. Fax: (404) 639-1174. E-mail: ceh4{at}cdc.gov.


Journal of Virology, August 2005, p. 9799-9809, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9799-9809.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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