Evaluation of a confidential method of excluding blood donors exposed to human immunodeficiency virus

A confidential self-administered questionnaire was given to all donors prior to blood donation (n = 95,917). The questionnaire describes acquired immunodeficiency syndrome (AIDS) high-risk groups and requires the donor to designate his blood for either laboratory purposes or for transfusion. Six-hundred and twenty-seven people (0.65%; 78% men) designated their blood for laboratory purposes. In addition to routine enzyme-linked immunoassay (EIA) screening for human immunodeficiency virus (HIV) antibody, all units from the latter group of donors were tested by Western blot (WB) irrespective of the EIA result. An equal number of donor units was selected from those designating their blood for transfusion (age, sex and clinic matched) and these too were tested by WB irrespective of the EIA result. We found that donors designating their blood for laboratory purposes had a 10 times (vs transfusion-designated controls) to 100 times (vs general donor population) greater exposure to HIV. In the laboratory-designated group, an EIA negative donor was WB positive, yielding an estimated EIA false-negative rate of 16 per million. A confidential questionnaire, as described, is a valuable adjunct in ascertaining high-risk blood donors.     

Screening potential blood donors at risk for human immunodeficiency virus

Even though all blood donated for transfusion is tested for the presence of human immunodeficiency virus (HIV) antibodies, there exists a period of time after infection by the virus before these antibodies can be detected. Blood donated during this window period is capable of transmitting the virus. Therefore, the blood of persons who are at risk for acquired immune deficiency syndrome (AIDS) should not enter the blood supply. Over a period of 4 months, 6573 potential blood donors who entered fixed and mobile blood collection sites in two cities were exposed to alternative interventions the aim of which was to exclude persons at risk for AIDS. We compared the interventions to one another and to existing materials in terms of the numbers of at-risk persons who did or did not donate for transfusion, the amount of attention paid to the materials, the scores on a comprehension test, and the self-reports by the subjects of attitudes towards the various interventions. At-risk donors who were asked direct AIDS risk behavior questions in addition to the current health history questions were more likely to be screened out than those who underwent alternative health history interviews (p less than 0.01). Potential donors paid more attention to the experimental brochures than to the experimental video or current materials (p less than 0.05). Comprehension scores were better for the new brochure and the video than for the current brochure (p less than 0.05). Donors were not offended by the experimental interventions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiologic characteristics of blood donors with antibody to human immunodeficiency virus

From March 1985 through July 1986, blood donors who were positive for antibody to human immunodeficiency virus (HIV) were evaluated at three major blood centers in the United States. Of 818,629 donations, 450 (0.05%) were HIV antibody-positive. The seroprevalence decreased from 0.07 to 0.04 percent during the study period, due perhaps to a decline in repeat donors. HIV-seropositive donors tended to be 20 to 29 years old (52%) and male (88%). HIV seroprevalence among white donors (2/10,000 donations) was less than that among Hispanic (9/10,000; p less than 0.0001) and black donors (31/10,000; p less than 0.0001). Of 152 seropositive men interviewed, 77 percent reported sexual contact with men; of this latter group, 53 percent were bisexual. Fifteen (44%) of 34 seropositive women had apparently acquired infection from heterosexual contact, and an equal number denied having any known risk factors for HIV infection. Educational efforts must address women and bisexual men who do not perceive themselves to be at risk for HIV infection and should be specifically designed for the mores of different racial and ethnic groups.     

False-positive human immunodeficiency virus type 1 western blot tests in noninfected blood donors

Background: The manufacturers' criteria for a positive human immunodeficiency virus type 1 (HIV-1) Western blot (WB) test were recently revised to require reactivity to only two of the following bands: p24, gp41, and gp120/160. In a recent report, low-risk blood donors were identified in whom nonspecific reactivity to multiple env antigens in WB testing resulted in apparently false-positive WBs by these criteria. The present study was conducted to verify the existence of false-positive WBs among noninfected donors and to assess the extent of this problem. Study Design and Methods: Four donors classified as WB- positive on the basis of env-only (3 cases) or p24/env-only (1 case) patterns were investigated. Index and/or follow-up specimens were tested by polymerase chain reaction (PCR), by overlapping recombinant env antigens and synthetic peptides in enzyme immunoassays, and by deglycosylated and denatured antigen WBs. WB records from American Red Cross blood centers were reviewed to determine the frequency of env- only and p24/env-only patterns, relative to all positive WBs, from 1988 through 1993. Results: The four index-case donors denied risk and had stable WB reactivity during follow-up. HIV PCR was negative in all. Env reactivity was restricted to nonglycosylated gp41 epitopes; no gp120- specific reactivity was detected. For three of the four donors, env reactivity was mapped to a 20-amino acid N-terminal epitope of gp41. The rate of detecting WBs with these false-positive patterns increased from 0.6 percent of all positive WBs from 1988 to 1990 (4/776) to 8 percent in 1991 and 1992 (52/683), and then it declined to 6 percent in 1992 and 1993 (47/783). Env-only patterns predominated in 1991 and 1992, whereas p24/env-only patterns were more frequent following implementation of combined anti-HIV-1/HIV type 2 enzyme immunoassays in 1992. Conclusion: Low-risk blood donors can have false-positive results on WB tests. Increased detection of env-only and p24/env-only WBs appears related to the enhanced sensitivity of newer enzyme immunoassays to gp41 and p24 antibodies. Donors with these patterns should undergo follow-up testing to document the presence or absence of HIV infection.     

Potential deferral criteria predictive of human immunodeficiency virus positivity among blood donors in Thailand

Background: To develop deferral criteria to prevent human immunodeficiency virus (HIV) transmission by recently infected blood donors in the seronegative “window” phase, routine data on donors at a university hospital were examined for factors predicting seropositivity. Study Design and Methods: Records of all 281 HIV- positive blood donors from August 1987 through September 1991 were retrospectively compared with those of 1076 randomly selected control donors matched only by year of donation. Four controls were selected for each HIV-positive donor. Results: The prevalence of HIV in 102,684 donor units during the period rose from 0.02 percent in 1987 to 0.52 percent in 1991. Multivariable analysis revealed that male sex (odds ratio [OR] = 26.4), VDRL test positivity (OR = 3.0), age 21 to 30 years (OR = 2.2; referent: 16–20-year-old group), and replacement donorship (OR = 1.4; referent: voluntary donors) were independent factors significantly associated with HIV positivity among these donors (p < 0.05). Since replacement donorship cannot be avoided, only male sex, age 21 to 30 years, and VDRL test positivity were considered as potential criteria. When these findings were extrapolated to all donors in 1990 and 1991, those with all three or only two (excluding VDRL test, because the results are known only after donation) of these high- risk factors had HIV positivity probabilities of 2.2 and 1.0 percent, respectively. These probabilities were, respectively, 4.9 times (95% CI: 2.9 8.3) and 4.1 times (3.1, 5.4) the risk among other donors. However, applying such criteria would have eliminated 1.5 and 31.2 percent, respectively, of all HIV-negative donors in 1990 and 1991. The latter deferral proportion is too high to be acceptable. Conclusion: In Thailand, improved donor deferral criteria addressing sexual risk factors could lead to decreased probability of window-period donation, with an acceptable rate of deferral. Additional p24 antigen testing may be indicated for donors at increased risk for HIV infection, specifically, men aged 21 to 30.     

Donation deferral criteria for human immunodeficiency virus positivity among blood donors in northern Thailand

Background: The purpose of this study was to develop human immunodeficiency virus (HIV) infection donation deferral criteria for blood donors in an HIV-epidemic area of northern Thailand, where the predominant means of transmission of HIV is through heterosexual contact. Study Design and Methods: In a preliminary study, 2242 blood donors were interviewed, and their blood was tested for HIV antibodies between September 1993 and April 1994. The risk factors associated with HIV positivity were identified. Criteria to identify HIV-positive persons on the basis of a logistic equation were developed and applied to another group of 5769 prospective blood donors. Results: A multivariate analysis showed the following odds ratios (OR) for traits that were independently associated with HIV positivity: younger age (OR = 0.93 for each additional year of age), male gender (OR = 2.41), having no more than a primary school education (OR = 2.00), being in the military (OR = 1.78), being unsure of one's own blood safety (OR = 2.00), history of injecting drug use (OR = 5.36), diagnosis of syphilis or positive syphilis serologic test in the past 12 months (OR = 2.67), and genital ulcer in the past 12 months (OR = 4.56). On the basis of the model, with a limit of <10 percent loss of uninfected donors, predicted probabilities of HIV positivity alone or of markers of infection with HIV, hepatitis B virus, or Treponema pallidum were calculated. With a cutoff of 6.5-percent estimated probability of HIV infection, derived from the logistic equation, the donor deferral criteria have 33.6-percent sensitivity and 8.3-percent positive predictive value for HIV positivity and 15.5-percent sensitivity and 18.4-percent positive predictive value for markers of infection with one of the three pathogens. Conclusion: The proposed donor deferral system provides a more flexible, sensitive, and predictive tool for averting donation by those who, though HIV antibody-negative, are at a higher risk of being infected with HIV.     

IgA and IgM human immunodeficiency virus antibodies in weakly reactive or false-negative blood donors

Detection of antibodies to the human immunodeficiency virus (HIV) in recently infected donors is crucial to prevent the transmission of HIV infection via blood products. To determine whether specific antibodies of the IgA or IgM class are present as markers of recent infection in donor specimens that have borderline reactivity on routine enzyme immunoassay (EIA) screening, 15 specimens that were positive by immunoblot were tested for IgA and IgM HIV antibodies. All 15 had detectable IgA HIV antibodies, and 14 had IgM HIV antibodies. The 15 specimens were tested further, each by two independent laboratories, with nine licensed EIAs. Two of the nine EIAs found all 15 units positive in both laboratories; seven EIAs found 1 to 5 of the 15 units negative, for a total of 31 false-negative results. The results indicated a difference between the sensitivity of EIA kits using only anti-IgG reagents and of kits using multispecific reagents that react with IgG and other classes of antibody. In a modified procedure, the addition of enzyme-conjugated anti-IgA or anti-IgM to the kit's enzyme-conjugated reagent increased the optical density values of most false-negative specimens to the positive range. It was concluded that licensed kits vary in reactivity with IgA and IgM HIV antibodies and that sensitivity could be increased by improved detection of these classes of antibody.     

Evaluation of the persistence and characteristics of indeterminate reactivity against hepatitis C virus in blood donors

BACKGROUND: A substantial number of individuals are excluded from blood donation due to indeterminate results in screening tests for hepatitis C virus antibody (anti-HCV). Disclosure of the characteristics of the indeterminate serologic pattern could optimize the testing and the management and care of blood donors.
STUDY DESIGN AND METHODS: Ninety-two former blood donors deferred from blood donation due to consistent reactivity in anti-HCV enzyme immunoassay and indeterminate HCV recombinant immunoblot assay (RIBA) results were retested for anti-HCV to examine the extent of disappearance of reactivity. In addition, they were screened for selected viral, immunologic, and inflammatory variables to detect possible causes of the test reactivity pattern.
RESULTS: After a median observation time of 75 months, 66 of 92 individuals had persistent indeterminate HCV RIBA results. Reactivity against the nonstructural NS5 antigen was the most frequent finding. A significant association was detected both between indeterminate reactivity in HCV RIBA and against the NS5 antigen independently and detectable antibody against adenovirus. Novel indeterminate reactivity showed increased prevalence during autumn and winter months.
CONCLUSION: Indeterminate HCV RIBA reactivity in blood donors persists over years. Increased prevalence during autumn and winter and association to detection of adenovirus antibody indicate that viral infection and cross-reactivity are etiologic factors in indeterminate HCV RIBA reactivity. Further prospective studies are needed to confirm the results.     

Direct oral questions to blood donors: the impact on screening for human immunodeficiency virus

BACKGROUND: In December 1990, the Food and Drug Administration recommended that all United States blood centers implement a policy of asking prospective donors direct oral questions (DOQs) about human immunodeficiency virus (HIV) risk behaviors to increase the safety of the blood supply. STUDY DESIGN AND METHODS: To evaluate the impact of the DOQ policy, HIV-related deferral and HIV seroprevalence data were analyzed at four American Red Cross blood centers for the year before the policy change and the year after. An epidemiologic analysis with stratification was conducted, including the calculation of odds ratios (OR) and 95-percent CIs. RESULTS: Two of the four blood centers showed an overall significant increase in HIV-related deferral after implementation of the DOQ policy: OR = 4.04, (95% CI = 3.41, 4.76); OR = 2.93, (95% CI = 2.67, 3.21). The increase in HIV-related deferral was higher for women. HIV seroprevalence decreased at all four centers, including the two that did not see an increase in HIV-related deferrals. Seroprevalence declined by 14 percent in the two centers with increases in HIV-related deferral, which was neither significant nor attributable to DOQs. CONCLUSION: Given that HIV antibody screening cannot detect HIV-seronegative (but infectious) "window-period" donations, the deferral of at-risk donors may offer some additional protection to the blood supply. However, evidence was not found of an increase in safety of the blood supply as measured by HIV seroprevalence.     

Evaluation of a confidential method of excluding blood donors exposed to human immunodeficiency virus: studies on hepatitis and cytomegalovirus markers

A confidential self-administered questionnaire was given to all blood donors prior to donation (n = 95,917). The questionnaire describes groups at increased risk of acquired immunodeficiency syndrome (AIDS) and requires the donor to designate his blood either for laboratory purposes or for transfusion. In a previous communication, we reported that donors in the former group had a much higher prevalence of antibody to human immunodeficiency virus (HIV) than age, sex and clinic matched controls or a group of "miscellaneous" donors who did not fill out the form properly. In this communication, we report results of tests for other viral markers performed on the three designation groups, namely laboratory-designated, miscellaneous and controls. We found that the former two groups had a higher prevalence of antibody to hepatitis B surface antigen (anti-HBs), hepatitis B core antigen (anti-HBc) and cytomegalovirus (anti-CMV) than controls, but there were no differences in alanine aminotransferase (ALT) levels among the groups. In addition, the laboratory-designated group had a higher prevalence of hepatitis B surface antigen (HBsAg) than the general donor population. These data indicate that a questionnaire designed to ascertain AIDS high-risk donors is valuable in excluding donors who may be carriers of other viruses as well.     

Evaluation of indeterminate c22-3 reactivity in volunteer blood donors

Background: Approximately 25 percent of blood donor sera that are repeatably reactive for hepatitis C virus (HCV) on second-generation enzyme immunoassay (EIA 2.0) are indeterminate on second-generation recombinant immunoblot assay (RIBA 2.0), and over 76 percent of these results are due to single reactivity to the HCV recombinant antigen c22- 3. Study Design and Methods: Data are presented on 46 volunteer allogeneic blood donors who were reactive on EIA2.0 and c22-3 indeterminate in RIBA 2.0. Index and follow-up samples were evaluated by using a panel of five synthetic peptide EIAs, a prototype strip immunoblot assay that uses synthetic peptides in addition to recombinant protein (RIBA 3.0), and polymerase chain reaction (PCR) for HCV RNA. Results: All 46 donations had normal alanine aminotransferase values; only 2 (4.3%) reacted for antibody to hepatitis B core antigen. With a panel of 12 synthetic peptides spanning the entire sequence of the c22-3 recombinant antigen, 33 plasmas (72%) reacted to one peptide or none, including 19 plasmas with reactivity restricted entirely to the N-terminal peptide (1–15 amino acids) of c22-3. With RIBA 3.0, 28 donations (61%) were nonreactive, including 25 that reacted with one peptide or none in EIA. Of these 25 plasmas, 18 reacted with the N- terminal sequence only. All 46 index donations were tested by PCR; the single PCR-positive unit reacted with four HCV peptides, was positive by RIBA 3.0, and reacted for antibody to hepatitis B core antigen. Twenty-six index donors were successfully recalled 3 to 7 months after their index donation. None seroconverted to positivity in RIBA 2.0, 1 was nonreactive, and 25 remained positive for c22-3 only. The restricted epitope reactivity in peptide EIA and RIBA 3.0 was maintained over time in all cases. All 26 of the follow-up samples tested negative by PCR. Conclusion: On the basis of the restricted peptide reactivity and PCR negativity of index and follow-up samples, it is concluded that the majority of c22-3 RIBA 2.0-indeterminate results are due to nonspecific cross-reactivity to restricted (principally, N-terminal) regions of HCV core antigen.     

Long-term follow-up of blood donors with indeterminate human immunodeficiency virus type 1 results on Western blot

BACKGROUND: At present, tens of thousands of United States blood donors who are at low risk for human immunodeficiency virus type 1 (HIV-1) infection are indefinitely deferred. These persons are repeatably reactive for HIV-1 antibody in enzyme immunoassay (EIA) and are indeterminate in Western blot. STUDY DESIGN AND METHODS: To determine the significance and persistence of anti-HIV-1 reactivity in plasma from volunteer blood donors with HIV-1-indeterminate Western blots, 66 donors were retested for HIV-1 antibody by the same manufacturers' EIA and Western blot 5 to 7 years after the initial Western blot. In addition, donors' peripheral blood mononuclear cells were tested by polymerase chain reaction (PCR) for HIV-1 DNA gag sequences. RESULTS: Thirty-five (53%) of 66 donors were still repeatedly reactive for HIV-1 on EIA and indeterminate on Western blot, 23 (35%) were negative on EIA and indeterminate on Western blot, 7 (11%) were negative in EIA and Western blot, and 1 (2%) was repeatedly reactive on EIA and negative on Western blot. Donors with persistently indeterminate Western blots had a band pattern nearly identical to that on the original Western blot. No donor was positive in Western blot, p24 antigen, or PCR testing. No donor had signs or symptoms of HIV-1 infection. CONCLUSION: Long-term follow-up of Western blot-indeterminate blood donors does not reveal evidence of HIV-infection. A mechanism to return these donors to the donor pool should be considered.     

Indeterminate human immunodeficiency virus type 1 western blot may indicate an abortive infection in some low-risk blood donors

BACKGROUND: The infectious status of persons with an indeterminate human immunodeficiency virus type 1 (HIV-1) Western blot must be established. STUDY DESIGN AND METHODS: Evaluation of the CD4 and CD8 T- cell subsets and the expression of HIV-1-integrated sequences by Southern blot and polymerase chain reaction were studied in a group of low-risk subjects with an indeterminate Western blot. RESULTS: From a total of 45,000 blood donors and 50 patients with chronic renal failure on hemodialysis who were tested during the period of 1985 through 1990, 50 sera (0.1%) had an indeterminate Western blot. A low CD4:CD8 ratio (0.7-1.2) was detected in 14 of 24 tested subjects, whereas the unfractionated and adherence-enriched cells of 7 (32%) and 5 (23%) of 22 patients, respectively, could be stained with a p24 monoclonal antibody. A transient positive culture was detected in 3 of 20 subjects, but these viral isolates could not be transmitted to CEM-A310 cells. Ultracentrifuged culture supernatants hybridized under high- stringency conditions with genomic gag-pol (4 cases), env (3 cases), and tat (1 case) cDNA fragments of the HXB2 HIV-1 clone. In one case, DNA obtained from adherent but not unfractionated mononuclear cells contained 3.3- and 3.9-kb env- and gag-pol-related HIV-1 sequences, respectively; these sequences were heavier than expected. Polymerase chain reaction analysis for gag and pol but not env sequences was positive in 1 and 2 of 7 cases, respectively. A female patient with a positive viral culture and who was positive for pol in polymerase chain reaction demonstrated a full seroconversion 19 months later. CONCLUSION: The results strongly suggest that, rarely, some low-risk subjects with indeterminate Western blot results might be infected with low-level replicative strains or HIV-related viruses; thus, an exhaustive immunologic and virologic workup is needed for the investigation of these subjects.