Transfusion-transmitted HIV Infection Research Articles

10-year analysis of human immunodeficiency virus incidence in first-time and repeat donors in Brazil.

Incidence in first-time and repeat blood donors is an important measure of transfusion-transmitted HIV infection (TT-HIV) risk. This study assessed HIV incidence over time at four large blood centres in Brazil. Donations were screened and confirmed using serological assays for HIV from 2007 to 2016, and additionally screened by nucleic acid testing from 2011 forward. Limiting antigen (LAg) avidity testing was conducted on HIV seroreactive samples from first-time donors to classify whether an infection was recently acquired. We calculated incidence in first-time donors using the mean duration of recent infection and in repeat donors using classical methods. Time and demographic trends were assessed using Poisson regression. Over the 10-year period, HIV incidence in first-time donors was highest in Recife (45·1/100000 person-years (105 py)) followed by São Paulo (32·2/105 py) and then Belo Horizonte (23·3/105 py), and in repeat donors was highest in Recife (33·2/105 py), Belo Horizonte (27·5/105 py) and São Paulo (17·0/105 py). Results from Rio de Janeiro were available from 2013 to 2016 with incidence in first-time donors of 35·9/105 py and repeat donors from 2011 to 2016 of 29·2/105 py. Incidence varied by other donor demographics. When incidence was considered in 2-year intervals, no significant trend was evident. Overall residual risk of TT-HIV was 5·46 and 7·41 per million units of pRBC and FFP transfused, respectively. HIV incidence in both first-time and repeat donors varied by region in Brazil. Clear secular trends were not evident.

Comparison of three immunoassay systems for screening of HIV infection in blood donation in China

Background: Preventing transfusion-transmitted HIV infection requires a sensitive and specific donor screening strategy. Currently, there is no public data to compare the performance of the two-different-EIAs strategy, the single-EIA and single-CLIA strategies for HIV donor screening in China. The aim of this study is to evaluate the performance of the three strategies. Methods: HIV Ag/Ab chemiluminescence microparticle immunoassay (ARCHITECT CMIA, Abbott Diagnostics, a version of CLIA) was performed on 2,138 samples. Western blot (WB) was used to confirm all samples with one or both EIA reactive or grey zone results and all samples with reactive Abbott CMIA results. The performance of the three strategies was evaluated by comparing testing results to HIV infection status as defined by WB positive results. Results: The positive and the negative coincidence rates of CMIA HIV Ag/Ab tests with confirmed HIV infection status were 98.41% (95% CI: 91.47–99.59%) and 99.32% (95% CI: 98.87–99.63%) respectively, equal or higher than EIAs. CMIA results yield the strongest correlation with HIV infection status. Conclusions: This is the first study to compare the performance of recently allowed single-EIA, single-CLIA donor screening strategy to the currently used two-different-EIAs strategy for HIV donor screening in China. Our results indicate that CMIA performed better than EIAs with a strong correlation with WB confirmed infection status. Implementation of one-CMIA strategy can further reduce the risk of transfusion transmitted HIV infection while decrease unnecessary waste of blood and permanent deferral of donor caused by false positive results.

Non-compliance to infectious disease deferral criteria among Hong Kong's blood donors.

Donor screening alone cannot eliminate the risk of transfusion-transmitted HIV infection. Donor deferral according to established criteria is a supplemental strategy, which has focused largely on men who have sex with men (MSM). A study was conducted to determine the compliance of non-MSM donors with such criteria and examine its implications on blood safety. Chinese donors who have just donated blood at blood donor centres in Hong Kong were recruited. Based on the contents of the routinely administered predonation Health Screening Questionnaires, participants were requested to complete a survey to assess their practice of deferrable risk behaviours and lifestyle encounters, using tablet computers. Over an 8-week period in mid-2016, 1614 donors (male-to-female ratio 1·23) had enrolled in the survey, accounting for 40% of donors giving blood on the survey days. The proportion of respondents who gave blood despite having deferrable HIV risk was 5%: MSM 1·2% (of the male donors); non-MSM risk behaviours 2·6%; risky lifestyle encounters 2·1%. If inconsistent declaration and suspected risk behaviours were included, the total non-compliance rate became 10·8%. Male donors had a higher prevalence of deferrable behavioural risk, even after excluding MSM. Unawareness and non-acceptability were main reasons for non-compliance. The non-compliance rate of donors to deferral was high, although the ultimate infection risk might be small in the presence of universal screening. Simplification of questionnaires, focus on time-limited deferral and a reduction of deferral items may improve the deferral mechanism without compromising blood safety.

Developing human capital in clinical research: Impact on reducing transfusion-transmitted HIV and hepatitis virus infections in Africa

Developing human capital in clinical research: Impact on reducing transfusion-transmitted HIV and hepatitis virus infections in Africa

Reevaluating Canada's policy for blood donations from men who have sex with men (MSM).

During the HIV/AIDS epidemic of the 1980s, most of the developed world instituted a permanent ban on blood donations from men who have sex with men (MSM). In recent years, public health agencies across Europe and North America are reconsidering and rescinding these restrictions. We examine the Canadian climate, where MSM may donate blood only after a 5-year deferral period. We review circumstances of the initial ban on MSM blood donations and recent social, legal, and economic changes that have encouraged Canadian public health officials to consider policy reform. We also review international evidence about the impact of reforming MSM blood donations. Given improvements in HIV screening technology, results from mathematical modeling studies, and empirical data from Italy, the UK, and Australia, we conclude that changing Canada's MSM blood donation policy from a 5- to a 1-year deferral would not increase the number of transfusion-transmitted HIV infections. We provide empirical support to the recently elected Liberal Canadian government's political promise to decrease restrictions on MSM blood donations.

The risk of transfusion‐transmitted HIV from blood donations of men who have sex with men, 12 months after last sex with a man: 2005–2007 estimates from England and Wales

The risk of transfusion-transmitted HIV infection under (i) permanent exclusion and (ii) 12-month deferral of MSM in England and Wales during 2005-2007 was estimated. Assuming equal compliance with both scenarios, estimated risk under a 12-month deferral (0.228/million donations [range 0·168-0·306/million donations]) was only marginally greater (0·5%) than that under lifetime exclusion (0·227/million donations [range 0·157-0.318/million donations]), with one extra-HIV infectious donation every 455years. Poorer compliance of MSM with a 12-month deferral would be expected to increase the estimated risk, whereas improved compliance could decrease risk by up to 29·1%.

Significant background rates of HBV and HCV infections in patients and risks of blood transfusion from donors with low anti‐HBc titres or high anti‐HBc titres with high anti‐HBs titres in Japan: a prospective, individual NAT study of transfusion‐transmitted HBV, HCV and HIV infections

The Japanese Red Cross (JRC) conducted a prospective study to evaluate the frequency of transfusion-transmitted HBV, HCV and HIV infections to assess the risk of transfusion of blood components routinely supplied to hospitals. Post-transfusion specimens from patients at eight medical institutes were examined for evidence of infection with HBV (2139 cases), HCV (2091) and HIV (2040) using individual nucleic acid amplification testing (NAT). If these specimens were reactive, pre-transfusion specimens were also examined for the virus concerned by individual NAT. In the event that the pre-transfusion specimen was non-reactive, then all repository specimens from implicated donors were tested for the viruses by individual donation NAT. In addition, a further study was carried out to evaluate the risk of transfusion of components from donors with low anti-HBc titres or high anti-HBc with high anti-HBs titres. Transfusion-transmitted HCV and HIV infections were not observed. One case of post-transfusion HBV infection was identified (rate, 0·0004675; 95% CI for the risk of transmission, 1 in 451-41,841). The background rates of HBV, HCV and HIV infections in patients prior to transfusion were 3·4% (72/2139), 7·2% (150/2091) and 0% (0/2040), respectively. Sixty-four anti-HBc- and/or anti-HBs-reactive blood components were transfused to 52 patients non-reactive for anti-HBc or anti-HBs before and after transfusion (rate, 0; 95% CI for the risk of transmission, <1 in 22). This study demonstrated that the current criteria employed by JRC have a low risk, but the background rates of HBV and HCV infections in Japanese patients are significant.

HIV Test Service in a Blood Center, as a Measure against Transfusion Transmitted HIV Infection

HIV Test Service in a Blood Center, as a Measure against Transfusion Transmitted HIV Infection

Preventing Transfusion-Transmitted HIV Infection in Latin America and the Caribbean: Issues Associated With Blood Donor Interviews and Sex Between Men

Blood-borne transmission is the most efficient route for acquiring HIV infection, particularly through transfusion. Availability of noninfectious blood units for hemotherapy is a necessary condition for efficient functioning of health services. They have the obligation to ensure that the blood supply is safe, which includes interviewing potential donors to ascertain whether they might be at risk of being HIV infected. The interview procedures demand that blood services staff inquire potential blood donors about sexual practices associated to HIV transmission. Assumptions and misconceptions may unnecessary exclude adequate donors. Review of published and unpublished country reports in Latin America regarding blood safety and deferral criteria related to same sexual behavior among males. An analysis of criteria for deferral of potential blood donors shows inconsistencies that may impact the necessary safe blood supply. The blood donor deferral criteria should be revised according to relevant epidemiological evidence and social legitimacy. Personnel in blood banks and hemotherapy services should be educated to conduct appropriate interviews for accepting or deferring potential donors. Potential donors and the public should be knowledgeable for them to understand the reasons why some individuals may be deferred. Health authorities should work to reduce the stigma associated with HIV, prioritize building strong and meaningful partnerships with civil society, and engage diverse sectors in the national AIDS response.

The Residual Risk of Transfusion-Transmitted HIV Infection in a Public Brazilian Blood Center.

Estimating risks of transfusion-transmitted infections is essential for monitoring blood safety and for helping physicians and patients decide about the risks/benefits of an allogeneic transfusion. In 2000, the residual risk of HIV in our institution was estimated in 1/325,000 units transfused and the prevalence of HIV among all blood donors was 0.06%. The goal of this study was to calculate the current residual risk of transfusion-transmitted HIV infection in the Regional Blood Center of Ribeirão Preto, University of São Paulo, Brazil. We evaluated 292,587 repeated donations of a total of 403,568 donations between january/2002 and december/2005. During this period, we identified 43 seroconversions among the repeated donors. The serological tests performed were 2 different enzyme immunoassays (EIA): HIV 1/2 and a conjugated p24 antigen/antibody as screening tests and Western Blot as a confirmatory test for all positive samples. In order to calculate the residual risk, we used the incidence rate/window period (IR/WP) model, developed in parallel by investigators from the National Heart, Lung and Blood Institute-sponsored Retrovirus Epidemiology Donor Study (REDS), the CDC and the American Red Cross. The IR takes into account the number of incident cases (numerator), the total number of repeated donations and the mean interdonation interval length (multiplication of the last two entities provides the number of person-years at risk or denominator). The mean interdonation interval length can be substituted for the mean seroconversion interval length for all incident cases if the first one can not be accurately measured, so we used this alternative. Once the IR is known, we calculated the residual risk dividing the IR by 365.25 days and then multiplying by the WP of the test used (p24=15 days). Our results are: IR= 43 cases/292,587 repeated donations × 3.2 years = 4.59×10−5. The current residual risk is (IR/365.25 days) × 15 days= 1.5/million units transfused or 1/667,000 units. The prevalence of HIV among all blood donors in 2005 was 0.035%. Although we know that the correlation between prevalence and residual risk is not straightforward, they have a certain degree of correlation and they both have declined since 2000. During these last 5 years, we have made some modifications in our donor selection towards a more rigorous donor screening and since january/2002 we have introduced the p24 antigen/antibody EIA as part of the screening serological tests. We concluded that the more stringent donor risk factor screening and the introduction of the p24 antigen test have substantially reduced the residual risk of transfusion-transmitted HIV infection in our institution.

Estimates of the frequency of HBV, HCV, and HIV infectious donations entering the blood supply in the United Kingdom, 1996 to 2003.

Several new tests have been recently introduced by the United Kingdom Blood Services to improve safety. The frequency (or risk) of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infectious donations entering the UK blood supply during 1996-2003 has been estimated. These years span the introduction of nucleic acid testing (NAT) for HCV, HIV combination antigen and antibody test and NAT for HIV. The frequency of an infectious donation entering the blood supply due to i) the window period, ii) assay failures and iii) human and technical errors in testing and processing, was estimated. The window period risk was estimated using the incidence of infection in donors and the length of the window period for tests in use, with an adjustment for atypical inter-donation intervals in seroconverting donors. The estimated frequency of infectious donations entering the blood supply during 1996-2003 was 1.66, 0.80 and 0.14 per million for HBV, HCV and HIV respectively. HCV NAT resulted in an over 95% fall in the risk of HCV. Current usage of HIV combined antibody-antigen tests and of HIV NAT reduced the estimated risk of HIV by 10%. Since 1996, the risk of transfusion-transmitted HBV, HCV and HIV infection in the UK has been lowered by several improvements to donation testing, although the absolute reduction in risk has been small. Vigilance for errors and the affects of donor selection may be as or more important than further reductions to window periods of tests for improving blood safety with respect to HBV, HCV and HIV.

Health status and health-related quality of life associated with hemophilia.

The hemophilias are a group of disorders associated with a chronic burden of morbidity and early mortality. Improvements in these adverse features have been achieved by the use of clotting factor concentrates within comprehensive centers of specialized care providing home infusion programs. Offsetting effects from transfusion-transmitted hepatitis and HIV infection are in recent decline. The net impact of these changes merits assessment. To test the a priori hypotheses that increasing severity of factor VIII deficiency would be associated with an increasing burden or morbidity and that hepatitis and HIV positivity would impair health status further, a cross-sectional study of a population-based cohort was undertaken in a regional hemophilia program in Ontario, Canada. A survey was made of mild, moderate, and severe hemophiliacs over 13 years of age who self-reported their health status using a standard 15-item questionnaire. The responses were converted to levels in the Health Utilities Index Mark 2 (HUI2) and Mark 3 (HUI3) health status classification systems to form multi-element vectors from which single-attribute morbidity and overall health-related quality of life utility scores were determined. The burden of morbidity was greater in hemophiliacs than in the general population and correlated with the category of disease (mild < moderate < severe). Hepatitis and HIV positivity conferred additional burdens of morbidity, which were mainly in the attributes of mobility (HUI2), ambulation (HUI3), and pain (HUI2/3), all of these differences reaching levels of statistical significance. Despite demonstrable improvements in the safety, effectiveness, and utilization of clotting factor concentrates, hemophiliacs continue to experience an important burden of morbidity. Measurement of this burden, as reported here, provides a basis for future economic evaluation of the costs and consequences of health care interventions provided to this population.

Redefining the HIV-infectious window period in the chimpanzee model: evidence to suggest that viral nucleic acid testing can prevent blood-borne transmission.

Although it is rare, blood-transmitted HIV infection can occur when a donor presents in the window period between HIV-1 exposure and the first appearance of detectable p24 antigen. To study this seronegative window period, a chimpanzee (X034) was inoculated with 38 median tissue culture infective doses of HIV-1 IIIB; serum and peripheral blood mononuclear cells were obtained one to two times per week for 12 weeks and then biweekly for 12 weeks. Infectivity was monitored by the detection of serum HIV RNA, cell-associated HIV DNA, p24 antigen, and anti-HIV and by co-culture methods. No HIV markers were noted until 5 weeks after inoculation, at which time virus was isolated and HIV RNA and DNA were detected in plasma and cells, respectively. Anti-HIV and HIV p24 antigen were not present until 8 weeks after inoculation. Plasma and cells obtained from Chimpanzee X034 3 or 4 weeks after exposure were then sequentially inoculated into a second chimpanzee (X176); no HIV infection was observed in this animal during serial follow-up for 24 weeks after each inoculation. In contrast, when the fifth-week HIV-1 RNA- and DNA-positive sample was inoculated, Chimpanzee X176 was unequivocally infected with HIV-1. Nucleic acid testing narrowed the seronegative window by 3 weeks (37%). More important, there was no demonstrable infectivity in either plasma or peripheral blood mononuclear cells obtained before molecular markers were detectable. This suggests that the infectious window may be considerably shorter than the total window as measured from exposure and that nucleic acid testing might not only shorten the seronegative window, but totally prevent transfusion-transmitted HIV infection.

Two successive HIV contaminations from subjects in the window period

We report a case of HIV seroconversion in a health-care worker, due to successive contaminations (i) from a blood donor to a recipient and (ii) from the recipient to the health-care worker. Unexpectedly, both infections occurred during the HIV serological window period. A nurse sustained a needle-stick injury with a large gauge hollow-bore needle on 24 January 1996. On the same day, she and the source patient were tested for anti-HIV antibodies by Genelavia Mixte (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) and Axsym HIV (Abbott laboratories, North Chicago, Illinois, USA) assays. The results were negative for both subjects. According to legal procedure, an HIV serology check was performed on the nurse 3 months after exposure. The presence of anti-HIV antibodies was observed by enzyme-linked immunosorbent assay and was confirmed by HIV-1 Western blot. Because the nurse reported no risk factors for HIV infection, HIV serology was again performed on a frozen sample from the source patient collected on the day of the needle-stick injury. This serum was found to be weakly positive (three times above cut-off) by Genscreen (Sanofi Diagnostics Pasteur), one of the most sensitive anti-HIV screening tests available [1]. p24 antigen was also positive with a high concentration (> 640 pg/ml). These results indicated that the patient was undergoing HIV seroconversion at the time of the nurse's exposure. The source patient, a 89 year-old woman who was hospitalized for a digestive bleeding, received six red cell units and two platelet concentrates between 6 December 1995 and the 28 January 1996. She died on the 2 February 1996. Sixteen out of the 17 implicated donors were traced, retested and found to be anti-HIV negative. The 17th donor did not answer to the inquiry, but HIV serology performed on 15 February 1996 in a hospital laboratory revealed the presence of anti-HIV-1 antibodies. His implicated donation was given on 24 November 1995 and was transfused to the patient on 6 December 1995. A frozen aliquot of this donation was investigated and was found to be anti-HIV-negative by Genscreen, p24 antigen-negative by Vironostika (Organon Teknika, Oss, The Netherlands), but was HIV RNA-positive by PCR (Amplicor, Roche, Branchburg, New Jersey, USA) and an in-house nested PCR performed in pol region. The results from the three subjects are summarized in Table 1.Table 1: . Data from three subjects implicated in two successive HIV contaminations.We describe an exceptional case of transfusion-transmitted HIV infection by a seronegative donor who was undergoing seroconversion and was in fact HIV RNA-positive. According to some predictions [2], this case highlights the capacity of nucleic acid amplification assays to eliminate the infectious but seronegative donors by reducing the length of the pre-seroconversion window period. Nevertheless, the cost and the complexity of such a measure in mass screening donations [3] must be balanced with the risk of transmitting HIV infection by transfusion of screened blood, which today is very small (1 per 1 million donations in France [4]). Because the precise date of the contamination is often unknown for HIV-infected patients, the length of window period is generally estimated by mathematical models [2]. In this transfusion-transmitted HIV infection, the interval from exposure to seroconversion was 49 days. The nurse was also infected by a subject in preserocon-version stage. The mean risk of transmission of HIV after percutaneous exposure has been estimated to be 0.3% with a higher rate when the HIV load in the source patient's blood is high [5]. Because the p24 antigen level was high and the injury was deep, it can be assumed that this was the case for this patient. On the other hand, if the source patient had been tested for p24 antigen in addition to anti-HIV antibodies, we can presume that the nurse would have been treated sooner by chemoprophylaxis. Thus, one of the recommendations for the improvement of the management of HIV post-exposure could be the implementation of a p24 antigen test in the source patient at the time of health-care worker exposure. Acknowledgement The authors thank F. Simon from the Virology Unit of the Hôpital Bichat, Paris, for performing nucleic acid analysis.

Retesting of bone donors 2 months after donation guarantees sufficient safety of bone allografts.

Both allogeneic bone grafting and blood transfusion may transmit infections from the donor to the recipient. The most effective means to reduce the risk of infection is careful donor selection and screening of donors for markers of infection. The risk of blood transfusion-transmitted HIV infection in Finland, calculated with the incidence/window period model, is approximately 1:3,300,000. The calculated risk for hepatitis B (HBV) and C (HCV) is 1:217,000 and 1:147,000 donations, respectively. In bone banking we can further reduce the risks by retesting the living donors. Retesting 2 months after donation seems to be sufficient, at least in countries with a low incidence of transplantation-transmitted infections.

Infectious disease testing for blood transfusions. NIH Consensus Development Panel on Infectious Disease Testing for Blood Transfusions

To provide physicians and other transfusion medicine professionals with a current consensus on infectious disease testing for blood transfusions.A non-Federal, nonadvocate, 12-member consensus panel representing the fields of hematology, infectious disease, transfusion medicine, epidemiology, and biostatistics and a public representative. In addition, 23 experts in hematology, cardiology, transfusion medicine, infectious disease, and epidemiology presented data to the consensus panel and a conference audience of 450.The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience.The panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature.The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference.The serum alanine aminotransferase test should be discontinued as a surrogate marker for blood donors likely to transmit posttransfusion non-A, non-B hepatitis infection since specific hepatitis C anti-body testing has eliminated more than 85 percent of these cases. Anti-hepatitis B core antigen testing should continue as it may prevent some cases of posttransfusion hepatitis B; it also may act as a surrogate marker for HIV infection in donors and may prevent a small number of cases of transfusion-transmitted HIV infection. Syphilis testing should continue until adequate data can determine its effect on the rarity of transfusion-transmitted syphilis. Vigilant public health surveillance is critical in responding to emerging infectious disease threats to the blood supply.

A model for estimating incremental benefits and costs of testing donated blood for human immunodeficiency virus antigen (HIV‐Ag)

We propose a model for estimating the benefit of adding a test for the human immunodeficiency virus antigen (HIV-Ag) to current procedures for testing donated blood. Using this model, data on HIV infection from published studies, and certain assumptions about blood donor behavior, we estimate that the probability of detecting an additional HIV-infective blood component is approximately 1 in 4,860,000. If this estimate is correct, adding HIV-Ag testing would prevent approximately 4 cases of primary transfusion-transmitted HIV infection annually in the United States. After adjustments for the median incubation period for AIDS, and for mortality due to primary illnesses, this estimate represents prevention of approximately 1 case of AIDS per year, within the 4 years after transfusion. A primary advantage of this model is its adaptability for recalculating cost-benefit analyses if more sensitive tests for HIV infection become available. In addition, we propose that comparing the anticipated costs and benefits of HIV-Ag testing to other possible uses of these funds should be an important factor in assessing the desirability of HIV-Ag testing.

Swedish transfusion medicine in a ten-year perspective--a brief review.

Although the scientific activity within blood preservation, plasma fractionation and treatment of coagulation disorders had been quite active in Sweden before 1978, the national coordination and self support with plasma products was insufficient. A programme for research and development was initiated in 1978 and resulted in important improvements. The production and use of blood components instead of the previous whole blood transfusion rose from 15% to 93% within 10 years and the supply of high quality plasma for industrial fractionation rose from 5,500 kg in 1978 to 86,700 kg in 1986. Transfusion transmitted HIV infection came as a new threat, first in haemophiliacs treated with imported coagulation factor concentrates, later also in patients treated with products from Swedish donors. After 1985 significant improvements were obtained by the introduction of anti-HIV testing of all blood donations and methods for virus reduction of fractionated plasma products. The use of more aggressive cytostatic therapy in haemotological malignancies has drastically increased the need of platelet concentrates for transfusion and has focused attention on platelet compatibility problems. The 10-year period 1978-87 has thus implied great changes in Swedish transfusion medicine with increased quality of haemotherapy and improved regional coordination.