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Recombination following superinfection by HIV-1

Fang, Guoweia; Weiser, Barbaraa,b; Kuiken, Carlac; Philpott, Sean Ma; Rowland-Jones, Sarahd; Plummer, Francise; Kimani, Joshuaf; Shi, Binshana; Kaul, Ruperte,f; Bwayo, Jobf; Anzala, Omuf; Burger, Harolda,b

Basic Science

Background: There is increasing recognition of recombinant HIV-1 strains globally, but it has been unclear whether recombination results from superinfection during untreated, chronic infection.

Objective: To search for evidence of recombination and superinfection in Africa, where multiple HIV-1 subtypes facilitate identification of strains.

Methods: Serial blood samples from highly exposed, chronically infected women in Nairobi's Pumwani sex workers cohort were examined. Serial, complete HIV-1 RNA sequence analyses were performed for seven untreated long-term survivors. Sequences were subjected to computational analysis.

Results: One woman had evidence of both superinfection and recombination. Complete HIV-1 RNA sequences were first derived from plasma obtained in 1986, when the woman had been HIV seropositive for at least 21 months; this sequence was entirely subtype A. The sequences obtained from plasma in 1995 and 1997, however, were subtype A/C recombinants with a SimPlot demonstrating that the subtype A fragment in 1995 and 1997 was derived from the original 1986 A sequence. Heteroduplex tracking assays demonstrated that the subtype C sequences were not detectable as minor species in 1986.

Conclusion: Intersubtype recombination took place between the original non-recombinant subtype A strain and the superinfecting subtype C strain in an untreated, chronically infected woman. This finding helps to explain the rising prevalence of recombinant HIV-1 worldwide. Recombination resulting from superinfection with diverse strains may pose problems for eliciting broad immune responses necessary for an effective vaccine.

From the aWadsworth Center, NY State Department of Health, Albany, the bDepartment of Medicine, Albany Medical College, Albany and cLos Alamos National Laboratory, Los Alamos, USA, the dInstitute of Molecular Medicine, University of Oxford, Oxford, UK, the eDepartment of Medical Microbiology, University of Manitoba, Winnipeg, Canada and the fDepartment of Medical Microbiology, University of Nairobi, Nairobi, Kenya.

Correspondence to Dr H. Burger, Wadsworth Center, 120 New Scotland Ave, Albany, NY 12208, USA.

Received: 22 May 2003; revised: 7 August 2003; accepted: 19 August 2003.

© 2004 Lippincott Williams & Wilkins, Inc.