Alan E. Williams

Retention of “safe” blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation.

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false‐positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple‐time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV‐infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple‐time donors giving 2,318,356 donations and observed for 822,426 person‐years, the HBsAg incidence rate was 4.01 per 100,000 person‐years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53‐percent chance that an HBV‐infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV‐infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person‐years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.

The retrovirus epidemiology donor study (REDS) : rationale and methods

BY THE SPRING OF 1984, it was clear that AIDS was caused by at least one retrovirus, initially called human T-cell lymphotropic virus, type 111 (HTLV-III), and later called the human immunodeficiency virus (HIV).. Shortly after HTLV-111 (HIV) was described, antibody enzyme immunoassays were developed. After these tests were introduced into blood bank practice in March and April of 1985, a significant number of HIV enzyme immunoassay-repeatably reactive results, many later confirmed as true-positive results, were enco~ntered.~ This finding was unexpected and raised serious concern, because blood bankers had believed that most people at high risk for AIDS had voluntarily refrained from donating blood and plasma.4- In 1985, a second strain of HIV was identified7 and designated HIV-2, with the original virus now called HIV1. A high degree (60-91%) of serologic cross-reactivity was exhibited against the original whole viral lysate enzyme immunoassays for HIV-1 antibodies8 To date, one blood donor infected with HIV-2 has been identified in the United States whose sera reacted with licensed HIV1 antibody screening tests,Y and one blood donor has been identified whose testing patterns suggested reactivity with HIV-2 antigens alone. No case of transfusion-transmitted HIV-2 has been reported in the United States. US Abbreviations: HIV-1 and -2 = human immunodeficiency virus type 1 and type 2; HTLV-I and -11 = human T-lymphotropic virus type I and type 11; HTLV-111 = HTLV, type 111, now HIV; MCC = medical coordinating center; NHLBI = National Heart, Lung, and Blood Institute; REDS = Retrovirus Epidemiology Donor Study; RFP(s) = request(s) for proposals; WBC(s) = white cell(s).

Evidence among Blood Donors for a 30-Year-Old Epidemic of Human T Lymphotropic Virus Type II Infection in the United States

The demographic and geographic determinants of human T lymphotropic virus types I and II (HTLV-I and -II) are not well defined in the United States. Antibodies to HTLV-I and -II were measured in 1.7 million donors at five US blood centers during 1991-1995. Among those tested, 156 (9.1/10(5)) were HTLV-I seropositive and 384 (22.3/10(5)) were HTLV-II seropositive. In contrast to monotonously increasing age-specific HTLV-I seroprevalence, HTLV-II prevalence rose until age 40-49 years and declined thereafter, suggesting a birth cohort effect. HTLV-II infection was independently associated with an age of 40-49 years (odds ratio [OR], 12.4; 95% confidence interval [CI], 8.8-18.9), female sex (OR, 3.3; 95% CI, 2.6-4.1), high school or lower education (OR, 1.7; 95% CI, 1.3-2.1), hepatitis C seropositivity (OR, 25.0; 95% CI, 17.5-35.8), and first-time blood donation (OR, 3.6; 95% CI, 2.8-4.7). HTLV-II seroprevalence was highest at the two West Coast blood centers. These data are consistent with a 30-year-old epidemic of HTLV-II in the United States due to injection drug use and secondary sexual transmission and with an apparent West Coast focus.

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process : the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion‐associated infectious diseases by allowing high‐risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T‐lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE‐) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE‐ (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed‐seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE‐ units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion‐transmitted infection become more difficult to identify by history‐based screening, however, such efforts may have limited effect.

Demographic characteristics, unreported risk behaviors, and the prevalence and incidence of viral infections: a comparison of apheresis and whole‐blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: The demographics, deferrable risk behaviors, and the prevalence and incidence of viral infections of apheresis (PH) and whole‐blood (WB) donors were compared, to characterize these two populations and to evaluate the relative safety of PH and WB donors in terms of transfusion‐transmitted viral infections.

Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users

This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CI] = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p less than 0.0002), fewer needle sharing partners (p less than 0.002), fewer sexual partners (p less than 0.03), and were more likely to be women (p less than 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk.

Loss of volunteer blood donors because of unconfirmed enzyme immunoassay screening results. Retrovirus Epidemiology Donor Study

BACKGROUND: Blood donors who test repeatably reactive on enzyme immunoassay (EIA) and are not confirmed as positive are a continuing problem for blood banks. Units are discarded and donors are deferred, in spite of multiple studies indicating that such donors are very rarely infected with the transmissible agents. Few data are available, however, with which to evaluate whether the discarded units are more likely to come from particular demographic subgroups. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study database of over 2 million allogeneic whole‐blood donations collected in the years 1991 through 1993 was utilized. The prevalence of false‐positive and indeterminate test results within demographic subgroups was computed for antibodies to human immunodeficiency virus, hepatitis C virus, and human T‐lymphotropic virus (anti‐HIV, anti‐HCV, anti‐HTLV, respectively) and hepatitis B surface antigen (false‐positive only) as the proportion of donations that were repeatably reactive on EIA but negative or indeterminate on the confirmatory or supplemental test. RESULTS: Several demographic groups with increased prevalence of false‐ positive and indeterminate anti‐HIV results were the same females, younger age groups, blacks, and first‐time donors. Likewise, many of the demographic subgroups with increased prevalence of false‐positive and indeterminate anti‐HCV results were similar: older age groups, non‐ whites, lower education levels, first‐time donors, donors making directed donations, and donors who had received transfusions. For anti‐ HTLV, by contrast, the oldest group had the highest prevalence of false‐ positive results but the lowest prevalence of indeterminate results: blacks had the lowest prevalence of false positive results but the highest prevalence of indeterminate results. CONCLUSION: If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex‐, race‐, and/or age‐linked proteins cross‐reacting with the test kit materials. Elucidation of these antigenic determinates and their subsequent removal should be a priority.

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

Background: 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.

Frequency of human immunodeficiency virus (HIV) infection among contemporary anti-HIV-1 and anti-HIV-1/2 supplemental test-indeterminate blood donors. The Retrovirus Epidemiology Donor Study.

Background: Follow‐up studies from the mid‐1980s showed that 1 to 5 percent of blood donors testing reactive in anti‐human immunodeficiency virus type 1 (HIV‐1) enzyme immunoassay (EIA) and testing indeterminate in Western blot were infected with HIV‐1 and were in the process of seroconverting. The present study was conducted to establish the rate of HIV infection among contemporary anti‐HIV‐1/HIV type 2 (HIV‐2) EIA‐ reactive, Western blot‐indeterminate donors.