HIV - Diagnosis, Early Infection Staging, and Recency Testing for Estimating Incidence

Early studies include application of viral culture and novel PCR methods to pooled seronegative donor samples and studies of serial samples from acutely infected participants in the gay male cohort studies to determine the timing of detection of HIV RNA and p24 Ag in plasma and DNA in cells, as well as HIV antibodies detectable by 2nd and 3rd generation immunoassays. The Fiebig Staging system and access to seroconversion panels has enabled characterization of transmitted founder viruses and the evolution of HIV in the context of evolving host immune responses.

We also developed strategies to estimate HIV incidence from cross-sectional serosurveys based on detection of participants with recently acquired infections, requiring modifications of HIV antibody assays to delay detection of seroconversion relative to increasingly sensitive diagnostic assays based on detuning of assay protocols or avidity treatment of HIV+ samples prior to testing. This is now a major field of recency assay development funded by NIH and the Bill and Melinda Gates Foundation.

Selected Publications:

Busch MP, Eble BE, Khayam-Bashi H, et al. Evaluation of Screened Blood Donations for Human Immunodeficiency Virus Type 1 Infection by Culture and DNA Amplification of Pooled Cells. N Engl J Med, 325:1-5, 1991.

Busch MP, Lee LLL, Satten GA, Henrard DR, Farzadegan H, Nelson KE, Read S, Dodd RY, Petersen LR. Time Course of Detection of Viral and Serological Markers Preceding HIV-1 Seroconversion; Implications for Blood and Tissue Donor Screening. Transfusion, 35:91-97, 1995.

Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, Heldebrant C, Smith R, Conrad A, Kleinman SH, Busch MP. Dynamics of HIV Viremia and Antibody Seroconversion in Plasma Donors: Implications for Diagnosis and Staging of Primary HIV Infection. AIDS, 17(13):1871-9, 2003.

Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM..., Busch MP, et al. Identification and Characterization of Transmitted and Early Founder Viruses in Primary HIV-1 Infection. PNAS USA, 105(21):7552-7, 2008.

Stramer SL, Glynn SA, Kleinman SH, Strong DM, Caglioti S, Wright DJ, Dodd RY, Busch MP, for the NHLBI Nucleic Acid Test Study Group. Detection of HIV-1 and HCV Infections Among Antibody-Negative Blood Donors by Nucleic Acid-Amplification Testing. N Engl J Med, 351(8):760-8, 2004.

Busch MP, Glynn SA, Stramer SL, Strong DM, Caglioti S, Wright DJ, Pappalardo B, Kleinman SH, for the NHLBI-REDS NAT Study Group. A New Strategy for Estimating Risks of Transfusion-Transmitted Viral Infections Based on Rates of Detection of Recently Infected Donors. Transfusion, 45(2):254-64, 2005.

Janssen RS, Satten GA, Stramer SL, Rawal BD, O’Brien TR, Weiblen BJ, Hecht FM, Jack N, Cleghorn FR, Kahn JO, Chesney MA, Busch MP New Testing Strategy to Detect Early HIV-1 Infection for Use in Incidence Estimates and for Clinical and Prevention Purposes. JAMA, 280(1):42-48, 1998.

Busch MP, Pilcher CD, Mastro TD, etal, for the WHO Working Group on HIV Incidence Assays. Beyond Detuning: Ten Years of Progress and New Challenges in the Development and Application of Assays for HIV Incidence Estimation from Surveys. AIDS 24(18):2763-2771, 2010.