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: 3.23). 03/1995; 35(2):91-7. DOI: 10.1046/j.1537-2995.1995.35295125745.x
Source: PubMed


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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    • "HIV antibody assays can show seroconversion within approximately 22 d of infection (but can be as long as 6 mo), with NAT detection reducing the window period for detection from 5.6 to 10.2 d (i.e., 4– 15 d in which infection is detected by NAT but not ELISA). HBV surface antigen (HBsAg) ELISA assays have a window period of 38.3 to 49.7 d, with NAT in the range of 20.4 to 25.7 d (Busch et al. 1995Busch et al. , 2005Schreiber et al. 1996;Pillonel et al. 1998;Kolk et al. 2002;Biswas et al. 2003;Fiebig et al. 2003;Kleinman et al. 2003;Kleinman and Busch 2006;Yao et al. 2007Yao et al. , 2008). The use of HBV NAT testing may detect HBV infection in donors who are HBSAg negative. "
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    ABSTRACT: Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients' recent and distant epidemiological exposures and all factors that contribute to the patient's net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future.
    Preview · Article · Oct 2013 · Cold Spring Harbor Perspectives in Medicine
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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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    ABSTRACT: With improved HCV therapy, challenges regarding HCV diagnosis, such as seronegative window period, false positive readings, and differentiation between recent, chronic, and resolved infections, are of increasing importance. To address these challenges an innovative device—SMARTube HIV & HCV—was used. Blood samples were tested for anti-HCV antibodies before and after incubation in the SMARTube, which promotes the in vitro stimulation of in vivo HCV primed lymphocytes, thus enhancing levels of anti-HCV antibodies. Comparing antibody levels, in concordant samples before and after SMARTube, yielded the Stimulation Index (SI). Among 5888 fresh blood samples, from various populations and regions worldwide, 641 were seropositive using plasma, while SMARTube processing (yielding enriched plasma, termed SMARTplasma) enabled diagnosis of 10 additional carriers in high-risk cohorts, that is, earlier detection. Using SMARTplasma eliminated all false positive results, using the current assays. In addition we show that SI calculation may serve as an important tool for differentiating between those who recently seroconverted, carriers of long-term infection, and those who have cleared the virus. SMARTube and the SI could lead to better, more informative diagnosis of HCV infections and play an important role in changing the way we treat both the infected individuals and the epidemic as a whole.
    Full-text · Article · Feb 2013 · The Scientific World Journal
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    • "The number of incident cases (numerator) was the number of donors who gave a negative donation followed by a confirmed positive blood donation. The window periods for anti-HIV, HIV-NAT, anti-HCV, HCV-NAT, and HBsAg (EIA, CLIA) were obtained from previous reports (Table 1) [3-7]. The incidence rate for each virus was multiplied by the length of the window to calculate the residual risk of infection [4,6-8]. "
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    ABSTRACT: Background Despite screening blood donations with advanced technologies and improved donor screening, the risk of transfusion-transmitted infections persists. This risk is mainly due to blood donations collected during the window period. A precise estimate of the transfusion risk of viral infection will help to determine the effect of new and current safety measures and to prioritize and allocate limited resources. Therefore, we estimated the risk of transfusion-transmitted viral infection in blood donations collected in Korea from 2000 to 2010. Methods Blood donations collected at 16 blood centers were tested for HIV, HCV, and HBV to estimate the residual risk of transfusion-transmitted viral infection. The residual risk was calculated in two-year periods using the incidence/window model. The incidence rates for HIV/HCV and the confirmed positive rate for HIV/HCV in first-time and repeat donors were compared. Results The residual risks for HIV in 2004/2005 and 2009/2010 were 1 in 1,080,244 and 1 in 1,356,547, respectively. The risks for HCV in 2000/2001 and 2009/2010 were 1 in 81,431 and 1 in 2,984,415, and the risks for HBV in 2000/2001 and 2009/2010 were 1 in 45,891 and 1 in 43,666. These estimates indicate that the residual risks for HCV in Korea have declined 36.6-fold, and those for HIV and HBV have not improved significantly, compared to previous estimates. The odds ratios for HCV and HBV positivity in first-time donors compared to repeat donors were 11.8 and 19.6, respectively. Conclusions The residual risk of HCV declined over the last decade due to improved screening reagents, implementation of the nucleic acid amplification test, and tight application of strict donor selection procedures. Current residual risk estimates for HIV and HCV in Korea are extremely low, but the risk for HBV is still high; therefore, urgent measures should focus on decreasing the residual risk of HBV. Despite the introduction of more sensitive assays in blood screening, several other factors may influence the actual residual risk of transfusion-transmitted infection. A continuous monitoring of residual risk of transfusion-transmitted infection is crucial in managing blood safety.
    Full-text · Article · Jul 2012 · BMC Infectious Diseases
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