FDA seeks temporary blood donor changes
Concern lies with group O HIV cases
Six months after two cases of HIV-1 group O infection were identified in the United States, the U.S. Food and Drug Administration has requested blood collection agencies to exclude donors who are at risk of the rare strain. The measure will be lifted once the FDA approves tests that are sensitive to group O.
Although group O appears to be exceedingly rare in this country, HIV tests licensed in the United States have failed to detect the strain reliably. The major strain in the United States is Group M, which includes subtypes A through I, with subtype B accounting for all but a few cases. How well commercial tests can pick up non-subtype B strains is not well-established.
"The FDA is very concerned about these [group O] cases, mainly because of lack of reliability of the current assays to identify these strains in the U.S.," says John Ward, MD, chief of the AIDS surveillance branch at the CDC.
The FDA recommendations emerged in December following a meeting of the agency’s Blood Products Advisory Committee.
"These recommendations should be considered interim measures to reduce the risk of HIV-1 group O transmission by blood and blood products pending the licensure of test kits specifically labeled for detection of antibodies to HIV-1 group O viruses," states Kathryn Zoon, PhD, director of the FDA’s Center for Biologics Evaluation and Research in a Dec. 11 letter to blood and plasma collection agencies.
A potential blood donor would be excluded from donations if he or she answers affirmative any of the following questions:
• Were you born in or have you lived in any of the following countries since 1977: Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, Gabon, Niger, or Nigeria?
• If you have travelled to any of those countries since 1977, did you receive a blood transfusion or any medical treatment with a product made from blood?
• Have you had sexual contact with anyone who was born in or lived in these countries since 1977?
The memorandum notes that the recommendations should be implemented immediately without prior approval by the FDA, and that blood and plasma collection agencies should submit proof that they are being established.
Blood donors already must answer a series of questions relating to activities that put them at risk of HIV. The new requirements, however, should not be too taxing, says Richard Davey, MD, chief medical officer for the American Red Cross.
"We hate to burden them additionally, but we feel that most of our donors are repeat donors and understand the necessity to answer these questions to protect the safety of the blood supply," Davey tells AIDS Alert.
The number of donors that would be disqualified by the new exclusion would be minute, he says, adding that more sensitive tests should come on the market soon.
"The questions are only a temporary measure," he says. "We are hoping it would be a matter of months, but certainly I would anticipate this would be in place by the end of 97."
A geographic exclusion was placed on blood donors earlier in the epidemic before tests were developed to screen HIV-2 virus.
Concerns about the existence of the group O virus in the United States were first raised in 1994, following reports that the strain had shown up in France and Belgium among individuals whose country of origin was in the West Africa region. Group O viruses were first identified in patients from Central and West Africa, primarily Cameroon. The strains were classified as group O (O standing for outlier) because of their genetic distance from other HIV-1 isolates.
Group O is considered rare outside of West Africa. Even in Cameroon, it accounts for only 8% of HIV infections that have been tested for the strain, says Ward. Two years ago, the CDC evaluated the sensitivity of FDA-approved HIV antibody screening tests to detect group O. The study found that several tests did not detect one or two of the eight group O sera specimens. All tests that use recombinant or synthetic peptide antigens failed to detect at least one specimen. Three of the five tests based on whole virus antigen did detect all eight specimens.
In July, the CDC reported on the first of two cases of group O virus identified in this country after investigating 72 people with AIDS living in the United States but whose country of origin was West Africa. Investigations were completed for 23 people, of whom seven died and 11 returned to their native countries. The first infection was found in a West African woman living in Los Angeles who was believed to have been infected while living in West Africa or by a West African sex partner. Neither of the two patients with group O strain reported having donated blood.
"This is a good example of the surveillance system in this country working really well," Davey says. "Here we have just two cases identified, and we are moving quickly now to update our screening test to take care of this problem."
Although the strain appears rare in this country, the CDC has not completed investigations on the remaining cases and other cases may show up. The strains harbored by the 72 patients were predominately non-subtype B, Ward says.
"We found that many of people tested so far actually have subtypes in Africa rather than those found here, which suggested they were infected in Africa or by sexual contact with people from Africa," he explains.
More sensitive test under development
Since notifying HIV test manufacturers in 1994 of the need to modify their tests, the FDA has required manufacturers developing new tests to enhance their sensitivity to group O viruses and to include group O specimens in their clinical evaluation. The FDA also is evaluating how sensitive the tests are to non-subtype B viruses. In conjunction with the CDC, it is developing good panels of sera from people with infections from other subtypes so there can be further study of test effectiveness.
"We know group O infections are not as reliably detected by the diagnostic testing used in this country," Ward says, "but we don’t know if other subtypes within group M, other than subtype B, are as reliably detected. The conventional wisdom is that since those subtypes are much more closely related, there should not be anywhere near the problem that is seen with group O."
Davey agrees: "We are in pretty good shape here in North America. The screening tests that have been developed are very effective against the prevalent subtypes here and we are not concerned we are missing others, but active surveillance is necessary."
The CDC will continue to monitor the prevalence of non-subtype B strains in the United States, not only to protect the blood supply but also because their prevalence may have ramifications for vaccine development. If other strains become more prevalent in the United States, researchers may need to develop a vaccine that will protect from strains other than non-subtype B, Ward adds.
Reference
1. Department of Health and Human Services. Letter from director of the Center for Biologics Evaluation and Research, Dec. 11, 1996.
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