In 1986, a second
virus causing the acquired immunodeficiency syndrome (AIDS), human
immunodeficiency virus type 2 (HIV-2), was discovered and found to be
relatively common in parts of West Africa. Because HIV-2 infections are
not always detected by HIV-1 antibody tests, antibody tests for HIV-2
have been developed. Voluntary screening for HIV-2 antibodies by blood
banks is a current acceptable practice. public health Department Clinics
now use a HIV1 and HIV2 Elisa test.
Although most HIV
infections in the United States are of HIV-1 group B subtype, current
ELISAs can accurately identify infections with nearly all non-B subtypes
and many infections with group O HIV subtypes. Infections with HIV-2 and
HIV-1 group O are rare in the United States and routine screening for
these subtypes is not generally recommended as part of diagnostic
testing except in areas where several such infections have been
identified. Routine screening for HIV-2 might be appropriate in certain
populations where potential risk for HIV-2 infection is higher (e.g., in
areas where West African immigrants have settled). Since June 1992, FDA
has recommended routine screening for antibody to HIV-2 (in addition to
HIV-1) for all blood and plasma donations. Clients with clinical,
epidemiologic, or laboratory history that suggests HIV infection and
negative or indeterminate HIV-1 screening tests should receive further
diagnostic testing to rule out HIV infection, potentially including
testing for HIV-1 non-B subtypes and HIV-2 .
Blood centers can
accomplish this either by the use of a single combination test for
HIV-1/HIV-2 or by the use of two independent tests, one for HIV-1 and
one for HIV-2. Screening donated blood and plasma for HIV-2 infection
raises issues concerning appropriate strategies for testing for both
viruses, HIV-2 testing in other settings, and notification of HIV-1 and
HIV-2 test results. What follows are CDC recommendations for the
diagnosis of HIV-1 and HIV-2 infections in persons being tested in
settings other than blood centers and CDC/FDA guidelines for serologic
testing with combination HIV-1/HIV-2 screening ELISAs.
Although HIV-2
appears to have spread in West Africa primarily via heterosexual
transmission, HIV-2 infection has been reported in Europe in homosexual
men, injecting drug users (IDUs), transfusion recipients, and men with
hemophilia. HIV-2 is endemic in parts of West Africa and has also been
reported in other parts of Africa. Apparently as a result of links with
former colonies in West Africa, Portugal and France have reported the
highest number of cases of HIV-2 infection in Europe. As of late 1989,
12.6% of AIDS cases in Portugal were caused by HIV-2. Although most of
these cases were in persons originally from Africa, HIV-2 is also
present among persons in Portugal with no known contacts with Africa.
HIV-2 infection has also been reported in India.
In the Western
hemisphere, rare cases of HIV-2 infection have been reported from
Brazil, Canada, and the United States. Within the United States, CDC and
others conduct surveillance for HIV-2, including serologic surveillance
of blood donors and populations at increased risk of HIV-1 infection.
Since 1987, 32
persons with HIV-2 infection have been reported in the United States.
Fifteen of these 32 were identified by serologic surveillance, and 17
were identified by case reports. Twenty-eight were residing in the
northeastern United States, a frequent destination for West African
immigrants and the area that has been most intensely surveyed using
HIV-2-specific tests. No cases of HIV-2 infection have been reported
among persons known to be IDUs or men reporting homosexual contact. More
than 2,700 serum specimens that were reactive by HIV-1 EIA and
indeterminate by HIV-1 Western blot have been tested for HIV-2 by either
the New York City Health Department or the Maryland Department of Health
and Mental Hygiene. HIV-2 infection was detected in specimens from 11
persons. The Massachusetts Department of Public Health identified two
HIV-2-positive specimens among blood samples from 14,779 childbearing
women. Positive HIV-2 specimens were detected among sera from two of
19,504 clients of sexually transmitted disease clinics, but in none of
the specimens from 6,547 IDUs at drug-treatment centers. In other
studies of populations at increased risk for HIV-1 infection, no cases
of HIV-2 infection have been reported. Of 15 U.S. residents found to be
positive for HIV-2 infection through serologic surveillance, demographic
information was available for seven; six were West Africans and one was
the U.S.-born wife of an HIV-2 infected West African.
Most of the 17
persons identified by case reports were West Africans residing in the
United States, but one was a U.S. resident of European origin and two
were native-born U.S. citizens. All three non-West Africans had traveled
to West Africa. One native-born U.S. citizen was diagnosed as HIV-2
infected after volunteering to donate blood in 1986. However, serologic
surveillance of more than 26,000,000 blood donations collected between
1987 and 1991 has not revealed another instance of an HIV-2 infected
U.S. blood donor.
DIAGNOSIS OF HIV-2 INFECTION
Although
considerable serologic cross-reaction occurs between HIV-1 and HIV-2,
HIV-2 infection may not be diagnosed when screening is done exclusively
with HIV-1 tests. From 60% to 91% of HIV-2-infected persons will test
repeatedly reactive by HIV-1 whole-virus lysate EIA. According to data
provided to FDA by the test manufacturers, HIV-2 antibodies are detected
with >99% sensitivity by FDA-licensed HIV-1/HIV-2 EIAs and the
FDA-licensed HIV-2 EIA. However, analogous to the diagnosis of HIV-1
infection, diagnosis of HIV-2 infection requires more specific
supplemental tests, such as an HIV-2 Western blot. Although no licensed
supplemental tests exist for HIV-2 infection, research tests are
available. Several European and U.S. biotechnology companies manufacture
HIV-2 Western blot tests. Studies of these tests have been performed by
manufacturers of HIV test kits, by state and local public health
laboratories, and by CDC. The diversity of protein bands, especially
glycoprotein bands, is greater on the HIV-2 Western blot tests than on
HIV-1 Western blot tests. This variation occurs because the various
HIV-2 Western blot tests use different strains of HIV-2 and because of
the different methods by which HIV-2 antigens are prepared before
separation by electrophoresis. No one test appears to have a distinct
advantage. Therefore, although public health laboratories would benefit
from a standard HIV-2 Western blot test format to which a single set of
interpretive criteria could be applied, a single standard currently
cannot be applied to all tests. CDC recommends that each test be
interpreted by the criteria suggested by the kit manufacturer.
Other
investigational tests for antibodies to HIV-2, such as
immunofluorescence, EIAs based on HIV-1 and HIV-2 synthetic peptides and
radioimmune precipitation can be useful in distinguishing a true
positive HIV-2 EIA screening test result. Gene amplification by
polymerase chain reaction and viral culture can also be used to
determine the virus type.
Persons at risk for HIV-2 infection include:
Sex partners of a
person from a country where HIV-2 is endemic (this category includes
persons originally from such countries).
Sex partners of a
person known to be infected with HIV-2.
Persons who
received a transfusion of blood or a nonsterile injection in a country
where HIV-2 is endemic.
Persons who shared
needles with a person from a country where HIV-2 is endemic or with a
person known to be infected with HIV-2.
Children of women
who have risk factors for HIV-2 infection or who are known to be
infected with HIV-2.
Additionally,
testing for HIV-2 is indicated when there is clinical evidence for or
suspicion of HIV disease (such as an AIDS-associated opportunistic
infection) in the absence of a positive test for antibodies to HIV-1 and
in cases in which the HIV-1 Western blot exhibits the unusual
indeterminate pattern of gag (p55, p24, or p17) plus pol (p66, p51, or
p32) bands in the absence of env (gp160, gp120, Or gp41) bands.
Other Considerations
Laboratories that
use a licensed combination HIV-1/HIV-2 screening test should follow the
testing algorithm recommended by CDC and FDA Figure 1. If a combination
test for HIV-1/HIV-2 is performed and is repeatedly reactive,
additional, more specific testing is necessary to confirm the presence
of antibodies either to HIV-1 or HIV-2 as follows:
A repeatedly
reactive specimen determined by a combination HIV-1/HIV-2 EIA should be
tested for antibodies to HIV-1 by a licensed Western blot or other
licensed HIV-1 supplemental test. A positive HIV-1 Western blot confirms
the presence of antibodies to HIV. Although this result does not always
distinguish between antibodies to HIV-1 and HIV-2, further testing is
not required for routine purposes. If the suspicion of HIV-2 infection
(based on epidemiologic risk factors {see "Recommendations" section}) is
high, additional testing for HIV-2 is indicated.
If the HIV-1
Western blot result is negative or indeterminate, an EIA for HIV-2 only
(HIV-2 EIA) should be performed. If the HIV-1 Western blot is negative
and HIV-2 EIA is not repeatedly reactive, the specimen should be
considered negative for HIV antibodies. If the HIV-1 Western blot is
indeterminate and the HIV-2 EIA is not repeatedly reactive, the specimen
should be considered indeterminate and the person should be advised to
have follow-up testing 6 months later to exclude the possibility of
early infection with HIV-1, especially if risk factors are present.
Persons should be counseled to follow risk-reduction guidelines during
the intervening 6 months. If the HIV-1 immunofluorescence assay (IFA) is
used as the supplemental test, positive and negative IFA results should
be interpreted in the same manner as similar results from Western blot
tests. However, with an indeterminate IFA (both infected and uninfected
cells fluoresce), neither positive nor negative interpretation of the
test is possible. Therefore, the specimen should be tested by HIV-1
Western blot. Further testing and counseling are determined by the
results of the Western blot.
If the HIV-2 EIA
is repeatedly reactive, an HIV-2 supplemental test should be performed.
Until an FDA-licensed supplemental test for HIV-2 becomes available,
specimens requiring supplemental testing for HIV-2 should be sent to the
appropriate state public health laboratory. Only those sera that are
repeatedly reactive by the combination HIV-1/HIV-2 test, negative or
indeterminate by the HIV-1 Western blot, and positive by the licensed
HIV-2 EIA should be sent for supplemental HIV-2 testing. An exception to
this rule would be a person with a positive result by HIV-1 Western
blot, but with demographic risk factors for HIV-2 infection.
Retesting with a
second specimen should be considered for persons who have positive
results by HIV-1 or HIV-2 Western blot at first testing.
MEDICAL COUNSELING
Infection with
either HIV-1 or HIV-2 can cause immunosuppression and the development of
AIDS (34,35). Although the period between infection and disease may be
longer for persons with HIV-2 than for those with HIV-1 (36,37), the
modes of transmission and, therefore, preventive counseling are the same
for persons with either virus. Furthermore, because data are limited
regarding the effectiveness of antiviral therapy for HIV-2 infection,
persons with a confirmed antibody test for HIV-2 should be managed
similarly to persons with a confirmed antibody test for HIV-1.
Additional testing to define the virus type is of epidemiologic
importance and should be considered for persons with epidemiologic risk
factors for infection with HIV-2.
