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Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection

Fiebig, Eberhard Wa,b; Wright, David Jc; Rawal, Bhupat Dd; Garrett, Patricia Ee; Schumacher, Richard Te; Peddada, Lorrainef; Heldebrant, Charlesf; Smith, Richardg; Conrad, Andrewg; Kleinman, Steven Hc,h; Busch, Michael Pa,d,i

Basic Science

Objectives: The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays.

Design: A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984–1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996–1998.

Setting: Two US plasma products companies.

Main outcome measures: The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection.

Results: The pattern of sequential emergence of viral markers in the ‘A’ panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the ‘B’ panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000–93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2–23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test.

Conclusion: The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.

From the aDepartment of Laboratory Medicine, University of California, San Francisco, CA, USA; bSan Francisco General Hospital Medical Center, San Francisco, CA, USA; cWestat, Inc., Rockville, MD, USA; dBlood Centers of the Pacific, San Francisco, CA, USA; eBoston Biomedica, Inc., West Bridgewater, MA, USA; fAlpha Therapeutic Corporation, Los Angeles, CA, USA; gNational Genetics Institute, Los Angeles, CA, USA; hUniversity of British Columbia, Victoria, BC, Canada; and iBlood Systems, Inc., Scottsdale, AZ, USA.

Correspondence and reprint requests to: Michael P. Busch, MD, PhD, Blood Centers of the Pacific, 270 Masonic Avenue, San Francisco, CA 94118, USA. Tel: +1 415 749 6615; fax: +1 415 775 3859; e-mail: mpbusch@itsa.ucsf.edu

Received: 1 August 2002; revised: 14 February 2003; accepted: 12 March 2003.

© 2003 Lippincott Williams & Wilkins, Inc.