Correspondence
The Risk of HIV Transmission by Screened Blood
N Engl J Med 1996; 334:992-993April 11, 1996
- Article
To the Editor:
The virtual elimination of the risk of transmitting the human immunodeficiency virus (HIV) by the transfusion of screened blood is a triumph of transfusion medicine, as the analysis by Lackritz et al. (Dec. 28 issue)1 shows. Remarkably similar data have emerged from a virologic analysis in which we directly determined the rate of HIV infection among donors that was not discovered because of the window period before seroconversion or because of errors during laboratory testing.
We isolated peripheral-blood mononuclear cells (PBMCs) from samples of 200,000 fully screened blood donations made available for virologic investigation from November 1, 1987, through June 15, 1993. Ficoll-separated PBMCs were combined into 50-donor pools, and multiple aliquots of pools containing 50 million PBMCs were frozen at -70°C for subsequent HIV culture, assay for HIV DNA by the polymerase chain reaction (PCR), or both.2 During phase 1, we cultured 50 million PBMCs from each of 2079 pools and in parallel performed standard “micro-PCR” tests using 250,000 PBMCs from a subgroup of 1516 pools. Interim analyses of the first 71,800 blood donations (tested through December 1989) revealed a single pool that was HIV-positive by culture and PCR.2
In phase 2, we screened 96,050 donations by testing 50 million PBMCs from each of 1921 pools of PBMCs, using a “macro-PCR” assay developed specifically for this study.3 A single pool that initially tested positive was negative on repeated macro-PCR and culture tests of backup aliquots. The unreported results from the 643 pools not already analyzed during phase 1, when combined with the results for the 1921 pools tested in phase 2, revealed no HIV infections among 128,200 blood donations collected between January 1, 1990, and June 15, 1993 (Table 1Table 1
Virologic Analyses of 50-Donor PBMC Pools Derived from 200,000 Voluntary Blood Donations at the Irwin Memorial Blood Center, San Francisco, November 1987 through June 1993.). A combined analysis of all the data from both phases of the study, after adjustment for the sensitivity of the algorithm used in the pooled testing,2 yielded a risk estimate of 1:160,000 (upper bound of the 95 percent confidence interval, 1:128,000).These data show a rapid and continuing decline in the risk of HIV infection as a cumulative outcome of the aggressive screening of blood donors and the improved sensitivity of laboratory tests.4 The similarity between the results of our experimental virologic studies and the epidemiologic risk estimates reported by Lackritz et al.1 should reassure both physicians and patients about the unprecedented safety of blood transfusion achieved by contemporary screening of our blood supply. (This work was carried out under a contract [HB-6-7020] with the National Heart, Lung, and Blood Institute.)
4 ReferencesGirish N. Vyas, Ph.D.
Bhupat D. Rawal, Ph.D.
Michael P. Busch, M.D., Ph.D.
University of California School of Medicine, San Francisco, CA 94143-01341
Lackritz EM ,Satten GA ,Aberle-Grasse J , et al. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995;333:1721-1725
Full Text | Web of Science | Medline2
Busch MP ,Eble BE ,Khayam-Bashi H , et al. Evaluation of screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells. N Engl J Med 1991;325:1-5
Full Text | Web of Science | Medline3
Babu PG ,Rawal BD ,Khayam-Bashi H ,Vyas GN . Detection of exceedingly low levels of HIV proviral DNA in multimillion peripheral blood mononuclear cells by PCR. PCR Methods Appl 1993;3:63-64
Medline4
Busch MP ,Lee LL ,Satten GA , et al. Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 1995;35:91-97
CrossRef | Web of Science | Medline
To the Editor:
The article by Lackritz et al. estimates that of the 12 million blood donations screened annually in the United States, from 18 to 27 are infectious for HIV. Of these, about 20 to 25 percent — that is, four to six infectious units — would be expected to test positive on the p24 antigen test and other screening tests.
Our laboratory acts as a reference laboratory for HIV testing in the Geneva area, and we tested 27 patients with diagnosed primary HIV infection for both HIV-specific antibodies and p24 antigen, both prospectively and retrospectively, from 1991 through 1994. Fifteen of the 27 tested positive, 2 had indeterminate results, and 10 tested negative on initial screening for HIV antibodies during the seroconversion period (third-generation enzyme immunoassay for HIV types 1 and 2, Abbott Laboratories, North Chicago, Ill.). When they were tested for p24 antigen, 24 of the 27 patients tested positive (HIVAG-1 Monoclonal, Abbott). Of the 10 patients with negative HIV-antibody results, all tested positive for p24 antigen.
Clinical data were available for all the seroconverting patients. We tried to assess whether using a more detailed questionnaire at the time of blood donation would have helped exclude patients with an acute retroviral syndrome, which is known to occur in 50 to 70 percent of patients.1 All 10 patients who tested negative for HIV antibody presented at the time of seroconversion with an acute retroviral syndrome of a mean duration of 16.8 days (range, 8 to 28). When we analyzed the symptoms and signs that were present on the day of the negative HIV-antibody test, we found that patients had been symptomatic for a mean of 5.8 days (range, 2 to 16) and that all had a maculopapular rash, 7 of the 10 had oral ulcers, and 5 of the 10 had genital ulcers.
More than a third of the patients undergoing seroconversion (37 percent) would not have been identified by a third-generation antibody test, but p24 antigen was detectable in all these antibody-negative patients. Clinical manifestations such as dermatologic signs, in particular a maculopapular rash, are clues that may be used to exclude seroconverting blood donors.1
1 ReferencesS. Kinloch, M.D.
L. Perrin, M.D.
B. Hirschel, M.D.
University Hospital, 1211 Geneva 14, Switzerland1
Kinloch-de Loes S ,de Saussure P ,Saurat JH ,Stalder H ,Hirschel B ,Perrin LH . Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 cases. Clin Infect Dis 1993;17:59-65
CrossRef | Web of Science | Medline
To the Editor:
The very small risk of HIV transmission through the transfusion of screened blood estimated by Lackritz et al. makes the policy of the Food and Drug Administration (FDA) that effectively prohibits blood donation by gay men indefensible. in 1983, when the cause of AIDS was not yet understood and the disease appeared to be linked to homosexuality, the FDA required blood banks to reject blood donations by men who answered “yes” to the donor-screening question, “Have you ever had sex with another man, even one time, since 1977?” Incredibly, this policy remains in effect, unnecessarily disqualifying many potential donors of healthy blood. . . .
Ben Carlson
1227 Guerrero St., San Francisco, CA 94110Author/Editor Response
The authors and a colleague reply:
To the Editor: Kinloch et al. provide important clinical and laboratory data on patients with primary HIV infection. Care must be exercised, however, when information on the performance of HIV-1 p24 antigen tests and clinical criteria for donor exclusion is extrapolated from clinically ill patients to U.S. blood donors. Before nonspecific criteria such as a history of rash are adopted as strategies for excluding blood donations, their specificity and positive predictive value should be carefully evaluated among potential donors. Similarly, the 100 percent sensitivity of the HIV-1 p24 antigen test reported by Kinloch et al. among clinically ill patients would probably not reflect the performance of the test among all persons during seroconversion. In a study of HIV seroconversion among persons at high risk, Busch et al.1 estimated that p24 antigen tests detected infection approximately six days earlier than the most sensitive HIV-1–antibody test, thereby identifying about 25 percent of people capable of transmitting HIV by transfusion but in whom levels of HIV antibody were not yet detectable.
The issue of donor exclusion raised by Mr. Carlson was not evaluated in our original report. Preventing blood donation by those potentially exposed to infectious diseases has been one of the cornerstones of the prevention of disease transmission to blood recipients. Questioning potential blood donors serves to identify those who have medical risks or have engaged in activities or behavior that is unquestionably associated with a risk of infection with HIV or another infectious agent. These policies and others, such as the exclusion of healthy persons who have traveled to areas with endemic malaria and those who have had hepatitis infection, disqualify many potential donors of safe blood but also remove from the donor pool those at increased risk for transmitting infectious diseases by transfusion.
In the United States, male–male sexual contact remains a leading risk factor for HIV infection.2 Despite the current questioning of donors and use of exclusion criteria, a study of 19 large U.S. blood centers revealed that 43 percent of all donations discarded because they were HIV-positive came from men who reported a history of male–male sexual contact.3 These data support the need to continue interviewing potential donors about behavior that presents a risk of HIV transmission.
3 ReferencesEve M. Lackritz, M.D.
Robert S. Janssen, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333Jay S. Epstein, M.D.
Food and Drug Administration, Rockville, MD 208571
Busch MP ,Lee LL ,Satten GA , et al. Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors. Transfusion 1995;35:91-97
CrossRef | Web of Science | Medline2
HIV/AIDS surveillance report. Vol. 5. No. 4. Atlanta: Centers for Disease Control and Prevention, 1994.
3
Lackritz EM, Kennedy MB, Doll LS, et al. Risk behaviors and test seeking among HIV-positive blood donors. Presented at the 48th Annual Meeting of the American Association of Blood Banks, New Orleans, November 11–15, 1995.
- Citing Articles (2)
Citing Articles
1
Steven H. Kleinman, Michael P. Busch. (2000) The risks of transfusion-transmitted infection: direct estimation and mathematical modelling. Best Practice & Research Clinical Haematology 13:4, 631-649
CrossRef2
Murphy, Busch, Tong, Cornett, Vyas. (1998) A prospective study of the risk of transfusion-acquired viral infections. Transfusion Medicine 8:3, 173-178
CrossRef
