Window Period Donations Research Articles

Detection of HCV and HIV‐1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing

To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS AmpliScreen HBV test

The risk of hepatitis B virus (HBV) transmission by blood transfusion (estimated at 1 in 63,000-1 in 205,000 units in the United States) exceeds that of hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Reduction of window-period HBV transmissions through detection of HBV DNA-positive units by minipool nucleic acid testing (MP NAT) would be expected to decrease this risk. A large multicenter study of the COBAS AmpliScreen HBV test (Roche Molecular Systems) was conducted on minipools of 24 blood donation specimens. The yield of HBV DNA-positive, hepatitis B surface antigen (HBsAg)-negative window-period donations was determined relative to current and newly licensed HBsAg assays. Donors with selected HBV DNA, HBsAg, and anti-hepatitis B core antigen (HBc) results were further evaluated. The detection rate of window-period units was 1 in 352,451 (95% confidence interval, 1 in 2,941,176-1 in 97,561). Assay specificity was high (99.9964%). HBV DNA was detected in 84 percent of HBsAg-positive, anti-HBc-positive donations by MP NAT and in 94 percent when individual-donation (ID) NAT was added. HBV DNA was detected in 0.03 percent of HBsAg-negative, anti-HBc-positive donations by MP NAT and in 0.41 percent when ID NAT was added. Implementation of HBV MP NAT will provide an increment in safety relative to HBV serologic screening, similar to that for HCV and in excess of that for HIV. Our data indicate that the implementation of HBV MP NAT would likely interdict 39 HBV window-period units and prevent 56 cases of transfusion-transmitted HBV infection annually. The current data indicate that HBV MP NAT should not lead to discontinuation of anti-HBc testing but that discontinuation of HBsAg testing with retention of anti-HBc testing may be possible.

Human immunodeficiency virus, hepatitis C and hepatitis B infections among blood donors in Germany 2000-2002: risk of virus transmission and the impact of nucleic acid amplification testing.

Blood and plasma donations in Germany are collected by several institutions, namely the German Red Cross, community and hospital-based blood services, private blood centres, commercial plasma donation sites and transfusion services of the army. All blood donation centres are required to report quarterly data on infection markers to the Robert Koch Institute, thus providing current and accurate epidemiological data. The prevalence and incidence of relevant viral infections are low in the blood donor population in Germany, with a decreasing trend for hepatitis C infections in new and repeat donors since 1997. The implementation of mandatory nucleic acid amplification technique (NAT) testing for hepatitis C virus (HCV) in 1999 has markedly improved transfusion safety. HIV-NAT became mandatory in 2004 but was done voluntarily by the majority of the blood donation services before then. The potential benefit of hepatitis B virus (HBV) minipool NAT is not as clear because chronic HBV carriers with very low virus levels might donate unidentified. The residual risk of an infectious window period donation inadvertently entering the blood supply can be estimated using a mathematic model which multiplies the incidence rate by the number of days during which an infection may be present but not detectable, i.e. the length of the window period. The risk of an undetected infection without NAT testing was estimated to be 1 in 2 770 000 for HIV, 1 in 670 000 for HCV and 1 in 230 000 for HBV in 2001/2002. This contrasts with 1 in 5 540 000 for HIV, 1 in 4 400 000 for HCV and 1 in 620 000 for HBV with minipool NAT testing. This demonstrates that NAT testing can further reduce the already very small risk of infectious donations entering the blood supply.

Should HBV DNA NAT replace HBsAg and/or anti-HBc screening of blood donors?

Prevention of transfusion-transmitted hepatitis B virus (HBV) has historically relied on serological screening of blood donors using progressively more sensitive HBsAg assays; in some countries anti-HBc assays have also been employed to detect chronic carriers with low-level viremia who lack detectable HBsAg. Nucleic acid amplification testing (NAT) for HCV and HIV has been successfully introduced to screen donors in many developed countries over the past several years; for logistical and cost reasons HCV/HIV NAT screening has been applied to mini-pools (MP) of eight to 96 donor specimens, with only minimal impact of MP dilutions on clinical sensitivity for interdiction of window period (WP) donations. In several countries (e.g., Japan and Germany), HBV NAT has been added to HIV/HCV MP-NAT blood donor screening with small incremental yields of HBsAg/anti-HBc-negative donations, and the major vendors of NAT systems (Roche and Chiron/Gen-Probe) have been developing triplex assays that include HBV DNA detection capacity without compromising HIV or HCV detection. Pooled specimen HBV NAT has also become the standard of practice for screening source plasma donors, with pressure to include HBV DNA detection as a required procedure for use of recovered plasma in manufacture of fractionated derivatives. However, there is controversy over the magnitude of the incremental yield and clinical benefit of HBV MP-NAT over serological screening strategies, as well as the impact of implementation of HBV NAT on need for retention of HBsAg and anti-HBc screening. This presentation will review recent modeled and empirical data on the value of HBV MP- and individual donation (ID)-NAT for detection of (1) pre-HBsAg WP units and (2) chronic anti-HBc-reactive carriers with undetectable HBsAg. The presentation will also review policy considerations and data that address the potential for discontinuation of either HBsAg or anti-HBc following implementation of HBV NAT. Finally it will address the cost effectiveness of incorporation of HBV DNA detection into HBV screening and NAT testing algorithms.

Pathogen inactivation of platelet concentrates and fresh frozen plasma

Transfusion of blood products carries the risk of pathogen transmission, despite careful donor selection and screening tests. This is due to viral transmission from window-period donations, the emergence of new pathogens such as variant Creutzfeldt-Jakob disease, for which routine screening tests are not yet available, and to bacterial contamination. Techniques have been developed to inactivate pathogens in both fresh frozen plasma and platelet concentrates. The relative benefits to the recipient, and the ease of incorporation into blood component processing are considered for the technologies currently available.

Laboratory strategic defense initiatives against transmission of human immune deficiency virus in blood and blood products

Serological methods based on enzyme linked immunosorbent assay (ELISA) and Western blot tests for detecting the presence of antibodies against the human immune deficiency virus are the standard techniques for identifying infected blood donors. However, these tests could not detect infected seronegative donors who were in the window period at the time of donation. Such donors can be identified by more elaborate methods including antigen detecting ELISA and polymerase chain reaction, which can detect viral antigens and nucleic acids in infected donor blood even in window period. In addition, the process of donor selection whereby individuals who were at high risk for HIV infections were excluded from the donor panel had substantially reduced the risk of window period donation. Furthermore, in order to ensure greater safety, transfusion centers nowadays undertake additional measures in the form of virucidal techniques such as the use of heat, detergents and photochemical agents to treat blood and blood products. Despite all of these measures, a risk-free transfusion was not practically achievable. However, risk-free transfusion is now possible with the introduction of recombinant blood products, the use of which is severely limited by their cost. Nonetheless, a risk-free transfusion is still achievable at a relatively little cost by transfusing suitably eligible patients with their own blood through the autologous blood transfusion program. Antibody testing is virtually the only method currently available in Nigerian blood banks. There is the need to reactivate and expand the scope of our National Blood Transfusion Service in order to make our blood and products safer.

A single window-period donation detected by human immunodeficiency virus p24 antigen after 5 years of routine screening in a group of Brazilian blood banks.

The purpose of this article was to describe the experience of screening for human immunodeficiency virus (HIV) p24 antigen (p24Ag) in blood donors, in four Brazilian Blood Banks, and to report the detection of the first window-period donation. During 61 months (May 96 to June 01), 103 470 consecutive donations were screened for HIV p24Ag using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Testing was carried out in accordance with the instructions supplied with the kits. Fifty-eight repeatedly reactive samples were identified [0.056% of the total; 95% confidence interval (95% CI): 0.042-0.070]. Ten of the 58 were confirmed as p24Ag positive after neutralization (0.010%; 95% CI: 0.004-0.016), nine of the 10 (0.009%; 95% CI: 0.003-0.014) were also HIV antibody positive and only one (0.001%; 95% CI: 0-0.003) was HIV antibody negative. In this setting the rate of sole p24Ag-positive donations was one in 103 740. This figure corresponds closely with the previously estimated yield of one in 87 796 donations. The yield of HIV p24Ag+ : Ab- has been previously estimated in our centres to be 1 : 87 796 donations, a value similar to that observed in actual practice.

Analysis of HBV infection after blood transfusion in Japan through investigation of a comprehensive donor specimen repository.

To understand the risk of transfusion-transmitted viral infection, it is important to precisely assess cases of infection that follow transfusion. HBV infections noted after transfusion in 1997, 1998, and 1999 were analyzed. Transfusion in all these cases was performed before NAT was adopted for donor screening. To detect viral infection, PCR and serologic tests for HBV were performed retrospectively on all blood samples from implicated donors that had been stored in a frozen state after each donation. The concentration of HBV genome was measured in HBV-positive blood samples. One hundred three cases of HBV infection were analyzed; of these, only 16, including at least 10 infections due to window-period (HBsAg-positive by reverse particle hemagglutination assay) donations, were confirmed by further testing to be related to transfusion. The concentrations of HBV genome were very low in four blood samples (<50, 400, 500, and 800 genome equivalents/mL of plasma). The remaining risk of transfusion transmission of HBV infection before the adoption of NAT was mainly due to window-period donations, including one that was made before the HBV genome was detectable by PCR. However, it was determined that transfusion was not responsible in many cases for HBV infection after transfusion.

Variant Creutzfeldt-Jakob disease in Australian blood donors: estimation of risk and the impact of deferral strategies.

In Australia, a policy of deferring donors who have lived in the UK for longer than 6 months between 1980 and 1996 has been instituted to reduce the theoretical risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) through the blood supply. The objective of this report was to refine estimates of the possible risks and benefits of donor-deferral strategies that are aimed at avoiding transmission of vCJD. Estimates of the effect of donor deferral on the blood supply in Australia were based on a 1998 survey of blood donors. The number of donations from donors potentially infected with vCJD and excluded by donor deferral was estimated based on published estimates of the size of the vCJD epidemic in the UK and assuming that the risk of vCJD in Australian blood donors was proportional to the time lived in the UK between 1980 and 1996. The possible increased number of blood donations that were infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) and made during a window period (as a result of increased donations from first-time donors) was estimated using published methods. A strategy of deferring donations in Australia from people who have lived in the UK for 6 months or longer, between 1980 and 1996, was estimated to result in exclusion of 5.3% of all blood donations, corresponding to 50 100 donations in 1998. It was estimated that the annual number of blood donations made by donors potentially infected with vCJD is 1.15 (range 0.02--31.1, based on the uncertainty in the UK prevalence estimate). Donor deferral was estimated to remove 0.92 (range 0.02--25.1) of these donations. Replacement of 33%, 50% and 100% of excluded donations by donations from first-time donors, was estimated to result in an increase of 0.0010, 0.0019 and 0.0044, respectively, of HIV-infected donations per year donated during the window period; in an increase of 0.021, 0.038 and 0.089, respectively, of HCV-infected donations per year; and in an increase of 0.18, 0.33 and 0.76, respectively, of HBV-infected donations per year. The large uncertainties involved in these analyses mean that estimates must be interpreted cautiously, but the data does suggest that donor deferral may exclude more donations from donors potentially infected with vCJD than the corresponding increase, caused by donor replacement, of window-period donations possibly infected with HIV, HCV or HBV.

Failure of Routine HIV-1 Tests in a Case Involving Transmission With Preseroconversion Blood Components During the Infectious Window Period

Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved. To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening. Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore. The blood donor and the 2 recipients of donor platelets and red blood cells. Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts. Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States. Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214

Optimal blood donation screening annotation.

Optimal blood donation screening annotation.

Results of Viral Marker Screening of Unpaid Blood Donations and Probability of Window Period Donations in 1997

Background and Objectives: To monitor the safety of the blood supply and evaluate the potential benefits of additional measures, the likelihood of virus transmission must be assessed. The European Plasma Fractionation Association and its member organisations have therefore developed a surveillance system to monitor infection markers among unpaid blood and plasma donors. We report and analyse the results of this surveillance for 1997. Materials and Methods: Data from the screening of unpaid donations for anti–HIV, anti–HCV and HBsAg during 1997 were collected retrospectively by EPFA member organisations. We identified seroconverters and estimate the probability of window period donations. Results: Data included screening results from 11 million unpaid donations in Europe, the USA and Australia. Prevalence of viral markers varied, with marker rates from repeat donations in Europe and Australia being significantly lower than in the USA. For first– time donations, in contrast, prevalence of HBsAg in the USA was within the ranges of those measured in Europe and Australia. Screening data of about 5 million European and 0.5 million Australian repeat donations were used to identify seroconverters. From the seroconverters that were detected among the European organisations, we estimated that 1 in every 2,323,778 repeat donations (range: 707,090–20,922,520) was made during the window period of anti–HIV screening. One in 620,754 (201,216–2,316,805) and 1 in 398,499 (155,209 to >1,088,511) repeat donations were made during the anti–HCV or HBsAg window period, respectively. Probabilities of window period donations in Australia were within the ranges of those measured in Europe. Conclusions: The collated surveillance data of 1997 illustrate the high degree of safety in blood and plasma products from unpaid donors.

Results of Viral Marker Screening of Unpaid Blood Donations and Probability of Window Period Donations in 1997

Abstract Background and Objectives: To monitor the safety of the blood supply and evaluate the potential benefits of additional measures, the likelihood of virus transmission must be assessed. The European Plasma Fractionation Association and its member organisations have therefore developed a surveillance system to monitor infection markers among unpaid blood and plasma donors. We report and analyse the results of this surveillance for 1997. Materials and Methods: Data from the screening of unpaid donations for anti‐HIV, anti‐HCV and HBsAg during 1997 were collected retrospectively by EPFA member organisations. We identified serocon verters and estimate the probability of window period donations. Results: Data included screening results from 11 million unpaid donations in Europe, the USA and Australia. Prevalence of viral markers varied, with marker rates from repeat donations in Europe and Australia being significantly lower than in the USA. For first time donations, in contrast, prevalence of HBsAg in the USA was within the ranges of those measured in Europe and Australia. Screening data of about 5 million European and 0.5 million Australian repeat donations were used to identify seroconverters. From the seroconverters that were detected among the European organisations, we estimated that 1 in every 2,323,778 repeat donations (range: 707,090–20,922,520) was made during the window period of anti‐HIV screening. One in 620,754 (201,216–2,316,805) and 1 in 398,499 (155,209 to &gt;1,088,511) repeat donations were made during the anti‐HCV or HBsAg window period, respectively. Probabilities of window period donations in Australia were within the ranges of those measured in Europe. Conclusions: The collated surveillance data of 1997 illustrate the high degree of safety in blood and plasma products from unpaid donors.

Assessment of Needs for Plasma for Fractionation in Europe

In the early 1990s, a series of outbreaks of hepatitis C (HCV) infections clustering among recipients of certain lots of plasma-derived medicinal products (PDMP) alarmed regulatory authorities, manufacturers and the public alike. Also, a few episodes of Hepatitis A (HAV) infections occurred in haemophiliacs receiving solvent–detergent-treated factor VIII concentrates. Thus, several measures were brought into effect to reestablish the safety of the incriminated products and to further increase the margin of safety of PDMP in general. Therefore, intramuscular immunoglobulins had to be free of HCV RNA as shown by nucleic acid amplification technology (NAT) in the final products. Furthermore, the manufacturing process of PDMP had to be validated for both viral inactivation and elimination. Finally, HCV-NAT was to be standardised and implemented as a validated test of plasma pool samples.In 1994, a joint meeting of EPFA, EAPPI and Regulatory Authorities was held in Brussels to outline the state of the art and to delineate the actions to be taken. Five years later, in 1999, the incidence rates of HIV, HBV and HCV in unpaid blood donors have been minimized, especially in European countries. With probabilities for window period donations as low as 0·6 in 1 million for both HIV and HCV and 2·1 in 1 million for HBV in Switzerland, labile blood products have reached extreme, but not absolute safety. The introduction of HCV-NAT roughly doubles this safety resulting in a 1 in 3 million probability of a window donation.Concomittantly, extensive viral validation studies document effective inactivation and removal of viruses in PDMP. The demonstrated margins of safety, expressed as logarithmical reduction factors (LRF), range from 4 to over 20 log10, depending on product, virus, and inactivation procedure used. Further progress to even safer PDMP shall be acomplished by consolidating the GMP processes, abandoning of obsolete requirements and harmonising national regulations within Europe. Before introducing new measures for additional agents such as HAV or Parvovirus B 19, gains and risks and even potential new threats have to be carefully assessed. Alternative efforts for the safeguard of patients, e.g. vaccination for HAV, need to be balanced against the risks of changing established and validated manufacturing procedures of PDMP with long-lasting safety records.

Transfusion-transmitted diseases: risks, prevention and perspectives.

During the past decades major improvements in blood safety have been achieved, both in developed and developing countries. The introduction of donor counseling and screening for different pathogens has made blood a very safe product, especially in developed countries. However, even in these countries, there is still a residual risk for the transmission of several pathogens. For viruses such as the human immunodeficiency virus (HIV), and the hepatitis viruses B and C, this is due mainly to window-period donations. Furthermore, the threat of newly emerging pathogens which can affect blood safety is always present. For example, the implications of the agent causing new variant Creutzfeld-Jakob disease for transfusion practice are not yet clear. Finally, there are several pathogens, e.g. CMV and parvo B19, which are common in the general donor population, and might pose a serious threat in selected groups of immunosuppressed patients. In the future, further improvements in blood safety are expected from the introduction of polymerase chain reaction for testing and from the implementation of photochemical decontamination for cellular blood products. The situation in transfusion medicine in the developing world is much less favorable, due mainly to a higher incidence and prevalence of infectious diseases.

Réflexions concernant le dépistage des acides nucléiques des virus des hépatites B et C et du virus de l'immunodéficience humaine dans la qualification biologique des dons

Direct viral DNA or RNA detection by genomic amplification methods should contribute to the improvement of blood supply safety by reducing the pre-seroconversion window period. However, nucleic acid testing may not eliminate virus transmission from window period donations. Moreover, the virus subtype diversity has to be taken into account for the choice of nucleic amplification assays. Technology for nucleic acid testing has not been developed to be implemented in blood screening laboratories. The limitations of these procedures are mainly linked to the difficulties related to the automation of sample processing and to the possibilities of cross contamination of samples due to the high sensitivity of amplification methods. The extreme complexity of nucleic acid testing for single donation screening (development of an on-site automated high-throughput instrumentation, training, specialized facilities for sample processing, amplification and detection...) and its high cost mean that strategies using amplification testing of pooled samples should be developed.

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group.

The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1-related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. Forty (18%) of 225 HIV-1-seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV-1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1-seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.

An estimate of the number of human immunodeficiency virus (HIV)-positive blood donations by HIV-seronegative donors in a northern Thailand HIV epicenter.

Despite mandatory antibody testing, human immunodeficiency virus (HIV) can be transmitted from HIV-infected blood that is seronegative. The objective of this study was to estimate the probability of HIV-infected blood donations during the seronegative "window period" in a northern Thailand HIV epicenter. Thus, a retrospective cohort of repeat blood donors was created. With the assumptions that the probability of HIV seroconversion is distributed uniformly between the last HIV-negative and the first HIV-positive donation and that the seronegative window is 45 days, the rate of window-period donations was calculated by multiplying the incidence by the window duration. Of 11,232 repeat donors, 273 seroconverted during 9,518,863 person-days of observation (i.e., a window-period donation rate of 1/775). There were more window-period donations among 21- to 30-year-old men and in donors replacing blood of friends or relatives. Additional measures are needed to reduce the high number of HIV-infected window-period donations.

Antigen testing for human immunodeficiency virus (HIV) and the magnet effect: will the benefit of a new HIV test be offset by the numbers of higher risk, test-seeking donors attracted to blood centers? Retrovirus Epidemiology Donor Study.

There currently is debate on whether to include new assays for viral antigens and nucleic acids in the battery of screening tests applied to all blood donations. Proposals call for implementation of p24 antigen screening tests to help identify donors who are infected with human immunodeficiency virus type 1 (HIV-1) but have not yet seroconverted (window-period donors). There is concern, however, that people at higher risk for HIV infection will be attracted to blood centers in order to obtain the results of an HIV assay that is not routinely available elsewhere. Therefore, the benefit of antigen testing may be offset by an increase in the HIV incidence rate among blood donors. Estimates were obtained from previous reports for the HIV incidence rate among blood donors, the percentage of donations from test-seeking donors, the duration of the HIV-infectious window period, and the performance of p24 antigen screening assays. Sensitivity analyses were performed by using various percentages of test-seeking donors following implementation of antigen testing and various HIV incidence rate ratios of test-seekers to nonseekers. Hypothetical residual HIV risks were calculated for multiple scenarios and compared to the current estimate of HIV risk without antigen screening of blood donations. If antigen testing reduces the window period by 27 percent (e.g., from 22 days to 16 days), and the HIV incidence rate among test-seekers is 30 times that among nonseekers, then the benefit of antigen testing will be eliminated if the percentage of test-seekers (currently estimated at 3.2%) increases to 5.7 percent. If antigen testing reduces the window period by approximately 45 percent (e.g., from 22 days to 10 days or from 13 days to 6 days) and the HIV incidence rate ratio (test-seekers vs. nonseekers) is assumed to be equal to the HIV prevalence ratio (5.3), then the percentage of donations from test-seeking donors would have to increase to 25 percent of all donations to offset the benefit of antigen screening. This model helps identify the key measures for assessing the potential adverse effect of increased test seeking as a consequence of the addition of p24 antigen (or other direct virus) assays to blood donor screening programs. In most scenarios, the beneficial effect of antigen screening exceeded the potential detrimental effect of attracting higher-risk, test-seeking donors. The possibility cannot be ruled out, however, that a subgroup of high-risk, test-seeking donors attracted to the blood centers by a new HIV test will offset the reduction in the residual risk of HIV infection associated with antigen screening.

Relationship between antibody to hepatitis B core antigen and retroviral infections in blood from volunteer donors

The value of the test for antibody to hepatitis B core antigen (anti-HBc) as a surrogate screening assay in the time before sensitive, virus-specific screening tests were available has been well established. There is significant debate, however about the residual value of anti-HBc screening after the implementation of human immunodeficiency virus (HIV)-, human T-lymphotrophic virus (HTLV)-, and hepatitis C virus (HCV)-specific assays and, in particular, about its utility as a lifestyle marker to identify persons at risk for retrovirus infections. Screening tests for antibodies to HIV, HTLV, and HBc, as well as confirmatory or supplemental test results for anti-HIV and anti-HTLV, were obtained from approximately 2.8 million donations collected from 1991 through 1993 by five blood centers within the United States. The sensitivity, positive predictive value, and relative prevalence of anti-HBc for each retrovirus were calculated and compared among demographic subgroups. The overall relationship between anti-HBc and anti-HIV was similar to that between anti-HBc and anti-HTLV. When calculated from the measured endpoint of the prevalence of anti-HIV-positive and anti-HTLV-positive donations, the sensitivities were 31.1 and 26.2 percent, the positive predictive values were 0.18 and 0.21 percent, and the relative prevalences were 30.1 and 23.8, respectively. Among 27 anti-HIV-seroconverting donors and 9 anti-HTLV-seroconverting donors, the sensitivities were 7.4 percent (95% CI: 0.9-24.3%) and 0 percent (95% CI: 0.0-28.3%), respectively. It was estimated that for each HIV-infected window-period donation detected by anti-HBc, from 19,000 to 81,000 HIV-noninfected donations are discarded. Similarly, more than 33,000 HTLV-noninfected donations are likely to be discarded for each HTLV-infected donation detected by anti-HBc. Although anti-HBc-reactive donations are more likely to be seropositive for a retrovirus than are anti-HBc-nonreactive donations, the low positive predictive value limits the test's effectiveness. If the anti-HBc test is retained in the blood donor setting, efforts should be focused on reducing the number of false-positive results.