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Journal of Virology, September 2005, p. 11693-11704, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11693-11704.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In-Depth Analysis of a Heterosexually Acquired Human Immunodeficiency Virus Type 1 Superinfection: Evolution, Temporal Fluctuation, and Intercompartment Dynamics from the Seronegative Window Period through 30 Months Postinfection{dagger}

F. E. McCutchan,1* M. Hoelscher,2 S. Tovanabutra,1 S. Piyasirisilp,1 E. Sanders-Buell,1 G. Ramos,1 L. Jagodzinski,1 V. Polonis,1 L. Maboko,3 D. Mmbando,4 O. Hoffmann,2,5 G. Riedner,5 F. von Sonnenburg,2 M. Robb,1 and D. L. Birx1

U.S. Military HIV Research Program, 1600 E. Gude Drive, Rockville, Maryland 20850,1 Department of Infectious Diseases and Tropical Medicine, Ludwig-Maximilians-University, Leopoldstrasse 5, Munich, Germany,2 Mbeya Medical Research Programme, Mbeya, Tanzania,3 Mbeya Regional Medical Office, Ministry of Health, Mbeya, Tanzania,4 London School of Hygiene and Tropical Medicine, 50 Bedford Square, London WC1B 3DP, United Kingdom5

Received 26 January 2005/ Accepted 18 June 2005

Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multiregion genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/µl at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasispecies, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.

* Corresponding author. Mailing address: U.S. Military HIV Research Program, 1600 E. Gude Drive, Rockville, MD 20850. Phone: (301) 251-5065. Fax: (301) 762-7460. E-mail: fmccutchan{at}hivresearch.org.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, September 2005, p. 11693-11704, Vol. 79, No. 18
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.18.11693-11704.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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