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Identification of HIV-1 Group O Infection -- Los Angeles County, California, 1996

The strains of HIV-1 that have caused the worldwide pandemic of acquired immunodeficiency syndrome (AIDS) have been designated as group M viruses. A group of HIV-1 viruses that also cause AIDS but that are characterized by extensive genetic divergence from group M strains have been identified recently and classified as group O viruses. Group O viruses or serologic evidence of group O infection have been reported in patients from West and Central Africa (Cameroon, Gabon, Niger, Nigeria, Senegal, and Togo), nationals of these countries living in Europe, and one French national (1-4). The antibody response elicited by group O strains is not consistently detected by enzyme immunoassay (EIA) kits commercially available in Europe and the United States (4,5). This report describes a patient in Los Angeles County, California, with recently confirmed HIV-1 group O infection in whom HIV infection was not detected consistently by standard HIV serology. *

Case Investigation

As part of CDC's national sentinel surveillance for unusual HIV variants, including group O infections, the Los Angeles County Department of Health Services (LACDHS) in April 1996 referred to CDC blood specimens obtained from a woman who had come to the United States from Africa and who had been reported to the LACDHS AIDS surveillance program in 1995. She was evaluated initially in November 1994 because of a 3-month history of generalized lymphadenopathy; lymph node biopsies obtained during March 1995 - June 1995 indicated lymphoid hyperplasia. In addition, in February 1995, she was tested for HIV infection by an Abbott ** HIV-1/2 enzyme immunoassay (EIA) for HIV antibody; the result was nonreactive.

In October 1995, she was evaluated again for persistent lymphadenopathy and for a 1-month history of menorrhagia. A platelet count was 7000 cells/uL, and findings of an examination of a bone marrow aspirate were consistent with idiopathic thrombocytopenic purpura. A test for antibody to HIV using an EIA from a different manufacturer (Genetic Systems HIV-1 EIA) was weakly reactive; however, the confirmatory Western blot was indeterminant (P17,P24,P31, equivocal gp41,P50,P66 bands present), and an HIV-2 EIA was nonreactive. The patient's CD4+ T-lymphocyte count was 132 cells/uL. When repeated 5 weeks later, findings were the same for the HIV-1 EIA (Genetic Systems) and Western blot; the CD4+ T-lymphocyte count was 92. In December 1995, a polymerase chain reaction assay for HIV-1 DNA was negative.

The patient had come to the United States and to Los Angeles County in 1994. She reported sexual contact with three men during her lifetime, including two in her country of origin during 1991-1994, and one (a native of Africa) in Los Angeles County during 1994-1995. None of the partners was known to be HIV-infected, to be bisexual, or to inject drugs. The patient reported one pregnancy in 1993 and that during the pregnancy both she and the father of the child had tested HIV-negative. She denied other HIV tests before or at the time of her arrival in the United States. The patient's baby was delivered by emergency cesarean section, and the patient did not know the quality of the procedures used to assure sterility of surgical instruments. She reported that the child and father continue to reside in Africa and are in good health. She denied a history of intravenous or other illicit drug use, occupational risks for HIV infection, and receipt of a blood transfusion. She had undergone scarification of her chest and back by a folk healer in 1985 for treatment of fever, and in 1991 for treatment of menstrual cramps. She reported that a razor blade was used in both procedures but did not know if these blades were sterile. She denied donating blood while residing in the United States.

Laboratory Investigation

At CDC, laboratory evidence for group O infection was established by HIV subtype-specific peptide serology (5,6), by culturing the virus from peripheral blood mononuclear cells of the patient, and by nucleic acid sequencing of the viral isolate. HIV subtype-specific peptide serology demonstrated that serum specimens from the patient reacted with two prototypic group O strains -- the V3 domain from ANT70 and the gp41 immunodominant region from MVP5180 -- but not with any peptides representing subtypes of the group M viruses. The nucleic acid sequences were analyzed by comparing the patient's viral nucleotide sequence with the sequences of prototype group O (ANT70 and MVP5180) and group M HIV viruses. When phylogenetic analysis was performed, sequences of the env, gag, and protease genes from the patient's isolate consistently and strongly clustered with the prototypic group O strains.

Commercially available diagnostic tests licensed by the Food and Drug Administration (FDA) were evaluated for their utility in detecting group O HIV infection in the patient. Serum samples obtained from the patient in April 1996 were tested using EIA assays from several manufacturers and by using reverse transcription-polymerase chain reaction (RT-PCR). Analyses performed at CDC and FDA laboratories indicated that antibodies to HIV-1 were detected by four of the five EIA kits tested (Table_1). Samples from the specimens obtained in October and November also were tested at CDC using the Genetic Systems HIV 1/2 EIA test; this kit failed to detect HIV infection in one sample (Table_1). HIV p24 antigen testing performed at CDC was negative on samples from specimens obtained in October 1995, November 1995, and April 1996. RT-PCR amplification to detect HIV RNA using standard HIV group M primers and probes (submitted to a commercial laboratory in May 1996) also was negative. However, a DNA PCR based on HIV-1 group O primers was positive at CDC.

Reported by: L Britvan, MD, K Gould, MD, J Dryjanski, MD, Kaiser Permanente Medical Group; P Kerndt, MD, L Mascola, MD, Los Angeles County Dept of Health Svcs, Los Angeles; R Sun, MD, S Waterman, MD, State Epidemiologist, California Dept of Health Svcs. Office of Blood Research and Review, Food and Drug Administration. Div of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention; Div of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: This report documents the first recognized case of HIV-1 group O infection in the United States. Although the source of the patient's infection is not known, her relatively recent arrival in the United States and low CD4+ T-lymphocyte count at the time of presentation suggest that she was most likely infected in Africa. Of the <100 group O infections reported worldwide, nearly all have occurred among persons from countries in West and Central Africa (7). In Cameroon, where the first group O strains were identified, group O strains have accounted for an estimated 6% of HIV infections (8). The worldwide distribution of these divergent strains is not well defined, but based on surveillance data, group O infection in the United States is rare. Among the 590,788 AIDS and HIV cases reported to CDC through December 1995, only 91 have been reported as occurring in persons born in countries in West and Central Africa from which group O infections have been reported. In addition, stored serum samples obtained from persons in both high and low HIV-risk groups in the United States and Puerto Rico were analyzed by a peptide EIA specific for the prototypic group O strains (MVP5180 and ANT70) (6); however, group O infections were not detected.

The differences in HIV-1 antibody test results for blood samples collected from this patient on several dates and analyzed by multiple HIV-1 EIA kits underscore variations in the ability of FDA-licensed EIA test kits to detect HIV group O infection. For example, testing using the Abbott HIV 1/2 EIA kit was nonreactive for a serum sample obtained in February 1995 (signal/cutoff {s/c} ratio of 0.7) but reactive for a sample obtained in April 1996 (s/c ratio of 1.2). Variability in s/c ratios is expected in weakly reactive specimens and may reflect kit lot variation and temporal changes in antibody titers in the patient. In addition, standard PCR testing (DNA-PCR and RT-PCR) was consistently negative, probably because of the use of primer sets designed to amplify group M HIV-1 strains.

Although the patient described in this report is the only known case of group O infection in the United States, the identification of HIV variants that are not detected consistently by all FDA-licensed HIV-EIA kits has important implications for medical diagnosis and blood safety. Current U.S. recommendations to prevent HIV transmission by blood and blood products include exclusion of donors with behavioral risk factors for HIV infection and screening of donated blood for HIV-1 and HIV-2 antibodies and for HIV-1 p24 antigen (9,10). The current practice of temporary exclusion of donors who have lived in or traveled through malaria-endemic regions may result in the exclusion of some donors at increased risk for infection with group O strains, which also are endemic in some malarious regions. In addition, FDA-licensed EIA test kits will identify many infections with group O HIV strains (5). Although manufacturers are working to reconfigure existing HIV-EIA tests to increase sensitivity for divergent HIV strains, modifications to increase sensitivity for group O variants must be monitored to assure that test accuracy for more prevalent HIV variants is not compromised. FDA and CDC are working with the manufacturers of HIV tests to ensure detection of all known HIV variants.

The recognition of this case of HIV-1 group O infection and the potential for emergence of other highly divergent strains underscore the importance of maintaining active surveillance for HIV variants at local, national, and global levels (6,7). To improve surveillance for and characterization of divergent HIV strains, CDC has established a domestic and global monitoring program for divergent HIV strains that are not reliably detected by the FDA-licensed tests.

Patients who present with clinical or laboratory findings suggestive of HIV disease, but for whom HIV screening tests are negative or equivocal, should be evaluated with further diagnostic tests to rule out HIV infection. Physicians evaluating such patients should consult with their state or local health department for assistance in characterizing risks for HIV exposure, defining prior history of blood donation, confirming the diagnosis of HIV infection, contacting sex partners, and, if necessary, characterizing the HIV strain.

References

  1. De Leys R, Vanderborght B, Vanden Haesevelde M, et al. Isolation and partial characterization of an unusual human immunodeficiency retrovirus from two persons of West-Central African origin. J Virol 1990;64:1207-16.

  2. Peeters M, Gaye A, Mboup S, et al. Presence of HIV-1 group O infection in West Africa {Letter}. AIDS 1996;10:343-4.

  3. Mulanga Kabeya C, Esu-Williams E, Eni E, Peeters M, Saman E, Delaporte E. Evidence for HIV-1 group O infection in Nigeria {Letter}. Lancet 1995;346:308.

  4. Loussert-Ajaka I, Ly TD, Chaix ML, et al. HIV-1/HIV-2 seronegativity in HIV-1 subtype O infected patients. Lancet 1994;343:1393-4.

  5. Schable C, Zekeng L, Pau CP, et al. Sensitivity of United States HIV antibody tests for detection of HIV-1 group O infections. Lancet 1994;344:1333-4.

  6. Pau CP, Hu DJ, Spruill C, et al. Surveillance for human immunodeficiency virus type 1 group O infections in the United States. Transfusion 1996;36:398-400.

  7. Hu DJ, Dondero TJ, Rayfield MA, et al. The emerging genetic diversity of HIV: the importance of global surveillance for diagnostics, research, and prevention. JAMA 1996;275:210-6.

  8. Zekeng L, Gurtler L, Afane Ze E, et al. Prevalence of HIV-1 subtype O infection in Cameroon: preliminary results {Letter}. AIDS 1994;8:1626-8.

  9. Food and Drug Administration. Revised recommendations for the prevention of human immunodeficiency virus (HIV) transmission by blood and blood products {Memorandum to all registered blood establishments}. Bethesda, Maryland: US Department of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Biologics Evaluation and Research, 1992.

  10. CDC. U.S. Public Health Service guidelines for testing and counseling blood and plasma donors for human immunodeficiency virus type 1 antigen. MMWR 1996;45(no. RR-2).

* Single copies of this report will be available until July 5, 1997, from the CDC National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD 20849-6003; telephone (800) 458-5231 or (301) 217-0023. 

** Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.


Table_1
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TABLE 1. Results of enzyme immunoassay (EIA) * antibody testing for HIV-1
in a patient infected with a group O variant of HIV-1 -- Los Angeles
County, California, 1996
=============================================================================
Date            Test result (S/C ratio +, Manufacturer)
-----------------------------------------------------------------------------
February 1995   Negative (0.7, Abbott HIV-1/2 EIA +)

October 1995    Positive (1.6, Organon Technica Corporation HIV-1 EIA)
                Negative (0.5, Genetic Systems HIV-1 EIA)
                Positive (1.4, Genetic Systems HIV 1/2 EIA)

November 1995   Positive (2.1, Organon Technica Corporation HIV-1 EIA)
                Negative (0.4, Genetic Systems HIV-1 EIA)
                Negative (0.9, Genetic Systems HIV 1-2 EIA)

April 1996      Positive (1.2, Abbott Recombinant)
                Negative (0.7, Organon Technica Corporation HIV-1 EIA)
                Positive (4.2, Genetic Systems HIV-1 EIA)
                Positive (3.4, Genetic Systems HIV 1/2 EIA)
                Positive (3.1, Abbott HIV-1 EIA)
-----------------------------------------------------------------------------
* Signal/cutoff ratio is the ratio of the sample optical density (OD) to the
  minimum OD required for a positive test (e.g., an s/c ratio of greater
  than 1.0 is required for a positive test).
+ Use of trade names and commercial sources is for identification only and
  does not imply endorsement by the Public Health Service or the U.S.
  Department of Health and Human Services.
=============================================================================

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