Busch, M.P. et al. Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 35, 91-97

University of Toronto, Toronto, Ontario, Canada
Transfusion (Impact Factor: 3.57). 03/1995; 35(2):91-7. DOI: 10.1046/j.1537-2995.1995.35295125745.x
Source: PubMed

ABSTRACT Almost all human immunodeficiency virus (HIV) transmission via blood or tissues that has occurred since anti-HIV screening was implemented in 1985 is traceable to blood given after infection but before antibody seroconversion, a time that is referred to as the window period. In this study, the performance of newer assays designed to detect viral and serologic markers soon after infection is assessed, and the reduction in the window period achieved by these assays is estimated.
Three cohort studies of persons at high risk for acquiring HIV infection were identified. These studies included well-controlled HIV type 1 (HIV-1) polymerase chain reaction (PCR) analyses of serial preseroconversion specimens from HIV-1-seroconverting homosexual men or intravenous drug users. Of 81 enrollees with anti-HIV-1 seroconversion documented by a viral lysate anti-HIV-1 enzyme immunosorbent assay (EIA) available in 1989, 13 (16%) had PCR-positive preseroconversion specimens. In the present study, sera from these 13 PCR-positive samples were further tested for anti-HIV by 10 contemporary EIAs and 6 supplemental assays, as well as being tested for plasma p24 antigen and HIV-1 RNA. Preseroconversion sera from 38 HIV-1 DNA PCR-negative cohort participants were also tested by selected anti-HIV EIAs and tested for p24 antigen and HIV-1 RNA. On the basis of these laboratory data and the intervals between blood drawing in all 81 men, the reduction in the preseroconversion window period achieved by these new assays was estimated with a mathematical model developed to analyze seroconversion data.
Nine (69%) of the 13 preseroconversion PCR-positive samples had anti-HIV that was detectable by one or more contemporary anti-HIV-1 or anti-HIV type 2 EIA. Supplemental antibody assays were negative on all four EIA-nonreactive preseroconversion samples and negative or indeterminate on a high proportion of the nine EIA-reactive PCR-positive samples. Eight (61%) of the 13 samples were p24 antigen-positive, and 11 (85%) were HIV-1 RNA-positive. The estimated reductions in the window period (relative to the index viral lysate-based anti-HIV EIA) were as follows: contemporary anti-HIV-1/2 EIAs, 20.3 days (95% Cl, 8.0-32.5); p24 antigen and DNA PCR, 26.4 days (95% Cl, 12.6-38.7); and RNA PCR, 31.0 days (95% Cl, 16.7-45.3).
Recent improvement in the sensitivity of anti-HIV assays has resulted in significant shortening of the preseroconversion window period. Consequently, the incremental reduction in the window period that could be achieved by implementing direct virus-detection assays has diminished significantly.

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Available from: Michael P Busch, Oct 09, 2014
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    • "In light of the above, finding a solution to the long WP remains an important goal in transfusion, transplantation, and diagnostic settings. Based on the fact that the long window period between HCV infection and detectable seroconversion is not due to lack of antigenic stimuli, it could be concluded that the WP is long, due to, at least in part, to specificimmune suppression [82]. Development of innovative technological solution which would overcome this immune suppression may lead to much needed progress in the field of earlier and better diagnosis of HCV infection. "
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    • "At that time there would be no, or almost no, virus detected in the blood. A link has been proposed between the time of active viremia in the blood reaching certain levels, and the time of seroconversion (Busch et al. 1995). The time between the infection and the active viremia reaching detectable levels in the blood is called the eclipse period. "
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    • "However, these findings were probably related to the testing methodology, were not verified in later studies [46] and were later withdrawn by the authors. First generation serological tests for HIV were less sensitive [47]; even so, most patients had detectable antibodies by three months [48]. Current 3rd generation assays generally detect infection by 30 days post-exposure [9]. "
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