A population-based surveillance registry was used to identify human immunodeficiency virus (HIV)-infected persons in the United States at increased risk for group O and group N infections (those born in or near African countries where group O infection has been reported). Of 155 eligible subjects, 37 gave samples. By phylogenetic and serologic analysis, 32 were infected with group M (16 with subtype A, 5 with B, 7 with C, and 1 each with subtypes D, F2, G, and recombinant A/J) and 2 with group O but none with group N virus. For 3, samples could not be typed by serology or amplified by polymerase chain reaction using group M-, O-, or N-specific primers. In the United States, group O HIV infection is uncommon; no case of group N infection was found. African-born persons may have HIV strains typical of their birth country. Ongoing subtype surveillance may allow early identification of novel or emerging HIV strains.

BACKGROUND: As of June 1, 1992, the Food and Drug Administration recommended that all donated blood be screened for antibodies specific to HIV‐2. Despite broad serologic surveillance, only two cases of HIV‐2 infection had been detected among potential blood and plasma donors since the implementation of the test. CASE REPORT: The identification of a third HIV‐2 antibody‐positive blood donor is reported. The first‐ time donor was identified by routine screening procedures as anti‐HIV‐ 1/HIV‐2‐reactive, and that status was confirmed by licensed HIV‐1 Western blot. Concurrent whole‐virus lysate enzyme immunoassay and Western blot for HIV‐2 were strongly positive, but the possibility of HIV‐1 cross‐reactivity could not be eliminated. The donor was notified, counseled, and deferred from future donation. He subsequently enrolled in a Centers for Disease Control and Prevention‐sponsored epidemiologic study of HIV‐positive former donors. When it was revealed during the standardized interview that he was a native of an HIV‐2‐endemic region, follow‐up samples were submitted to the Centers for Disease Control and Prevention. Investigational HIV‐1 and HIV‐2 peptide enzyme immunoassays indicated that this infection was due to HIV‐2 only. CONCLUSION: Enzyme immunoassays for antibodies to synthetic peptides of HIV‐1 and HIV‐2 may be useful in differentiating the two viruses in individuals with ambiguous Western blot results and risk factors for HIV‐2 infection.

In 1994, seven unusual cases of HIV infection were identified in France (1). These cases occurred in foreign nationals whose specimens had atypical Western blot patterns and weak or no seroreactivity in HIV-1 peptide or recombinant-based enzyme immunoassays (EIA). In previous cases, such isolates had been loosely grouped as phylogenetic outliers, termed Group O strains, highly divergent from the Group M strains that gave rise to the HIV-1 pandemic (2). The 1994 cases were soon recognized as representing the global emergence of genetically distinct viruses known to be circulating in Cameroon and Gabon. This recognition prompted an immediate reassessment of HIV screening in Europe and North America. Subtype B strains of HIV-1 predominate in Europe and North America, and there has been increasing evidence for the entry of non-B strains into these populations through persons who were infected while abroad. However, there was no evidence of indigenous spread of the strains in North America (3,4). We report here the laboratory findings related to the first documented HIV-1 Group O infection in the United States. The case was identified in April of this year through the CDC sentinel surveillance program for unusual HIV variants and involves a West-Central African woman (residing in the United States), with a 2-year clinical history of lymphadenopathy, thrombocytopenia, and progressive CD4 lymphocyte loss. In February 1995, the patient was tested for HIV-1-specific antibodies and was determined to be seronegative (Abbott HIV-1/2; signal/ cutoff value = 0.7) by recombinant-antigen based EIA. The patient's serostatus was reevaluated the following October and November and again in April of 1996 with inconclusive results (Table 1). On these occasions, whole virus lysate-based EIAs yielded negative or weakly positive results (signal/cutoff ratios were 0.68 to 4.20); however, confirmatory Western blot assays remained indeterminate. The November 1995 sample was negative in both Genetic Systems formats; however, a signal/cutoff ratio of 0.89 was noted. The Western blot pattern remained remarkably stable through the year, and the patient's sera remained HIV-1 antigen–negative on each sampling occasion. Attempts by commercial reference laboratories to amplify proviral sequences from the patient's peripheral blood mononuclear cells by standard Group M gag-specific primers for polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR did not show HIV sequences. To reconcile the serologic findings, a panel of HIV subtype–specific, peptide-based EIAs was performed at CDC (6) (Table 2). As points of reference, examples of results with sera representing the Group M subtypes A, B, C, D, E, and F are shown. A high degree of cross-reactivity exists among the Group M sera, with the strongest response usually directed against the V3 peptide from the subtype that infected the source patient. The exception to this (Table 2) is seen in the Brazilian subtype F sera, which react strongly with the subtype B peptide but not with the subtype F peptide, which was derived against subtype F isolates from Romania. The distinction between Brazilian and Romanian sera is reflected in the genetic diversity between isolates from the two regions (7). This broad seroreactivity among group M sera is also reflected in their response to group-specific peptides from the gp41. However, the patient's sera were only reactive to the Group O–specific V3 and gp41 peptides (OD = 1.704 and 2.467, respectively). This provided the first direct evidence that this patient was infected with a Group O variant. The virus CDC7755 was isolated by cocultivating the patient's peripheral blood mononuclear cells with phytohemagglutinin A, which stimulated nor-

BACKGROUND: Because occupational blood contact places health-care workers at risk for infection with bloodborne pathogens, we wanted to estimate the prevalence of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among hospital-based surgeons and correlate the results with occupational and nonoccupational risk factors,STUDY DESIGN: All surgeons in training or in practice in general surgery, obstetrics and gynecology, or orthopedics at 21 hospitals in moderate to high AIDS incidence areas were eligible to participate in a voluntary, anonymous serosurvey, Serum samples were tested for HIV antibody, for II(SV antibody, and for markers of HBV infection: hepatitis B surface antigen, total antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen,RESULTS: Of 2,887 eligible surgeons, 770 (27 percent) participated in the study, One of 740 surgeons not reporting nonoccupational risk factors was HIV seropositive (0.14 percent, upper limit 95 percent confidence interval [CI] equals 0.64 percent), None of 20 participants reporting nonoccupational HIV risk factors and none of ten not responding to the question on nonoccupational risk factors were HIV positive. Of 129 (17 percent) participants with past or current HBV infection, three (0.4 percent) had chronic HBV infection; all were negative for hepatitis B e antigen, Risk factors for HBV infection included not receiving hepatitis B vaccine (odds ratio [OR] 14.7, 95 percent CI 8.3 to 26.0) and practicing surgery at least ten years (OR 2.2, 95 percent CI 1.3 to 3.8), Seven (0.9 percent) participants had anti-HCV.CONCLUSIONS: Although not necessarily generalizable to all surgeons in moderate to high AIDS incidence areas, these results do not indicate a high rate of previously undetected HN infection among surgeons who trained or practiced in these areas, or both, Hepatitis B virus posed the highest risk of infection with a bloodborne pathogen, followed by HCV and HIV.

Objective. HIV-1 and HIV-2 isolates representing various geographic regions and distinct viral subtypes were examined for their ability to establish both in vitro and in vivo productive infections of Macaca nemestrina (pigtail macaque) peripheral blood mononuclear cells. Methods. Animals were inoculated with either autologous cell-associated or cell-free viral preparations of selected isolates. HIV-specific immune responsiveness, hematologic changes, genetic variation, and virus burden were monitored as delineators of HIV pathogenesis. Results. HIV-2 replication in vitro and in vivo correlated with nascent antigen production and rising viral titers as determined by infectious center assays. Infection was detectable by polymerase chain reaction amplification of proviral sequences in macaque cells as early as 1 week postinoculation. Two distinct patterns of CD4+ cell depletion induced by HIV-2 infection were observed during the first month postinoculation and characterized by a moderate loss sustained through 20 weeks postinoculation or a substantial loss maintained long-term (> 90 weeks). Identity between inoculating viral stocks and subsequent viral isolates from animals was established comparatively by limited sequence analysis of specific domains within the HIV-2 pol and env genes. In contrast, replication of HIV-1 isolates was limited or only semipermissive in vitro. Intravenous inoculation of HIV-1 field isolates, using conditions successful for HIV-2 (for example, identical viral titers), failed to establish a productive viral infection leading to seroconversion or fluctuations in hematologic cell markers. Infection with a high-titer inoculum of a laboratory-adapted HIV-1 strain in vivo, as demonstrated by polymerase chain reaction analysis, produced seroconversion in the absence of overt viral replication or hematologic variations in one out of four animals. Conclusions. This system provides for multifaceted modeling of HIV pathogenesis, primarily with HIV-2 and potentially with HIV-1/-2 chimerics, in support of immunotherapeutic developments and critical evaluation of intervention practices.

Objective: To study the risk for human immunodeficiency virus (HIV) infection and the patterns of use and associated toxicity of zidovudine among health care workers after an occupational exposure to HIV.Design: An ongoing, prospective surveillance project conducted by the Centers for Disease Control and Prevention.Participants: Exposed workers voluntarily reported by 312 U.S. health care facilities from August 1983 to June 1992.Results: Four of 1103 enrolled workers with percutaneous exposure to HIV-infected blood seroconverted (HIV seroconversion rate, 0.36%; upper limit of the 95% CI, 0.83%); no enrolled workers with mucous membrane (n = 75) or skin (n = 67) contact seroconverted. During October 1988 to June 1992, 31% of 848 enrolled workers used zidovudine after exposure; this proportion increased from 5% during October through December 1988 to 43% during January through June 1992. Despite using zidovudine after exposure, one worker became infected with a strain of HIV that was apparently sensitive to zidovudine. Adverse symptoms, most commonly nausea, malaise or fatigue, and headache, were reported by 75% of workers using zidovudine; 31% of workers did not complete planned courses of zidovudine because of adverse events.Conclusions: The risk for HIV seroconversion after percutaneous exposure to HIV-infected blood is 0.36%, which is similar to previous estimates. Zidovudine is used after exposure by a sizable proportion of health care workers enrolled in the project despite frequent, minor, associated symptoms. Documented failures of postexposure zidovudine prophylaxis, including in one worker enrolled in this study, indicate that if zidovudine is protective, any protection afforded is not absolute. Postexposure zidovudine, if used, requires careful consideration of possible risks and benefits.

Objectives. We conducted sentinel surveillance in persons practicing behaviors known to transmit retroviruses to determine the US presence and extent of human immunodeficiency virus type 2 (HIV-2).Methods. Sentinel surveillance for HIV-2 was conducted by testing 31 533 anonymous blood specimens from patients at sexually transmitted disease clinics, injecting drug users at treatment centers, and clients at HIV counseling and testing sites in 14 US cities where West African immigrants often settle. Specimens were tested by HIV-1 and HIV-2 whole virus and synthetic peptide enzyme immunoassay and confirmed by HIV-1 and HIV-2 Western blots.Results. Nearly 10% of 31 533 sera were positive for HIV-1. Two heterosexual Black male sexually transmitted disease patients were infected with HIV-2. One of the HIV-2 Positive specimens did not cross-react on HIV-1 enzyme immunoassay screening. One client had antibodies consistent with malarial infection in West Africa; the other, who had syphilis, did not have antibodies to malaria or to any of 20 arboviruses present in Africa.Conclusions. Clinics serving clients from HIV-2 endemic areas should test persons practicing risk behaviors for both HIV-1 and HIV-2. Sentinel surveillance for HIV-2 serves as an early warning system for the possible spread of this virus in the United States.

TOKARS, J. I.; CHAMBERLAND, M. E.; SCHABLE, C. A.; CULVER, D. H.; JONES, M.; McKIBBEN, P. S.; BELL, D. M.

We have studied longitudinally ten patients with AIDS encephalopathy with respect to pathogenetic roles of human immunodeficiency virus (HIV) and cytomegalovirus (CMV). Three patients manifested typical AIDS dementia complex (ADC) (initially without retinitis and with slowly progressive cognitive, motor and behavioral abnormalities which were zidovudine-responsive, and relatively preserved CD4+ T cells), and seven patients presented with AIDS dementia complex complicated by CMV encephalopathy (ACE) (with CMV retinitis, peripheral neuropathy, altered sensorium, and rapidly declining clinical and immunological status). Whereas only HIV antibody was elevated in the spinal fluid of patients with ADC, both virus infections were active in the central nervous system of patients with ACE as shown by HIV p24 antigenemia and antigenrrhachia, elevated HIV and CMV antibody in the spinal fluid, disseminated CMV infection with retinitis, and basilar ventriculoencephalitis with multinucleated cytomegalic cells containing CMV and HIV proteins and CMV DNA. The recognition of ADC and ACE is important, since some patients with ACE may respond to ganciclovir or foscarnet.

OBJECTIVE:To study the seroprevalence of human immunodeficiency virus (HIV) among orthopedic surgeons, and correlate the results with occupational and nonoccupational risk factors. Orthopedic surgeons are one of several groups of health care workers at risk for occupationally acquired HIV infection; however, few HIV seroprevalence studies in health care workers, and none in surgeons, have been performed to assist in estimating the extent of occupational risk. DESIGN:A voluntary, anonymous HIV serosurvey at an annual meeting. To assess the representativeness of participants, a mail survey of orthopedic surgeons was conducted 5 months prior to the annual meeting. SETTING:The 1991 annual meeting of the American Academy of Orthopaedic Surgeons held in Anaheim, Calif. PARTICIPANTS:United States or Canadian orthopedic surgeons in training, in practice, or retired from practice who attended the annual meeting. MAIN OUTCOME MEASURES:Participants' HIV serostatus and reporting of occupational and nonoccupational risk factors for HIV infection. RESULTS:Of 7147 eligible orthopedists at the annual meeting, 3420 (47.9%) participated. Compared with the 10,411 orthopedic surgeons responding to the mail survey, serosurvey participants had at least as many opportunities for occupational contact with blood and with HIV-infected patients. Among participants, 87.4% reported a blood-skin contact and 39.2% reported a percutaneous blood contact in the previous month. Among 3267 participants without reported nonoccupational risk factors for HIV infection, none was positive for HIV antibody (0%; upper limit of the 95% confidence interval [CI] = 0.09%); among 108 participants with reported nonoccupational HIV risk factors, two were positive for HIV antibody (1.9%; upper limit of the 95% CI = 5.7%). CONCLUSION:Although these findings may not be generalizable to all orthopedic surgeons, we found no evidence of HIV infection among serosurvey participants without nonoccupational risk factors. The high rates of self-reported blood contact underscore the importance of compliance with infection control precautions and of development of new techniques and equipment to minimize the risk of exposures to blood during surgical procedures.

BACKGROUND Routine, voluntary testing of hospital patients for the human immunodeficiency virus (HIV) has been proposed in order to identify those with early HIV infection in a setting where there is ready access to counseling, appropriate clinical referral, evaluation, and therapy. We studied the pattern of HIV infection among patients in 20 U.S. hospitals, in order to evaluate possible national strategies for the routine, voluntary HIV counseling and testing of hospital patients. METHODS Blood specimens remaining after clinical use from a systematically selected sample of patients at 20 hospitals in 15 U.S. cities were tested anonymously for antibody to HIV type 1 (HIV-1). Multivariate regression was used to determine which variables best predicted HIV seroprevalence in individual hospitals. Using these data, we estimated the number of HIV-positive patients in all U.S. hospitals and considered the efficiency of routine counseling and testing in different subgroups of patients and hospitals. RESULTS From September 1989 through October 1991, 9286 of 195,829 specimens (4.7 percent) were positive for HIV-1 in the 20 hospitals. The seroprevalence of HIV at these institutions ranged from 0.2 percent to 14.2 percent. Among HIV-positive patients, 32 percent had symptomatic HIV infection or the acquired immunodeficiency syndrome (AIDS) at the time of admission or evaluation. In the 20 hospitals, HIV seroprevalence was 10.4 times (95 percent confidence interval, 8.8 to 12.0) the AIDS-diagnosis rate (the annual number of patients with new diagnoses of AIDS per 1000 discharges in 1990). In a multivariate model that included 13 hospital-specific variables, only the AIDS-diagnosis rate was associated with the hospital-specific HIV-seroprevalence rate (P less than 0.001). Using these data and the AIDS-diagnosis rates for all U.S. acute care hospitals, we estimated that 225,000 HIV-positive persons were hospitalized (95 percent confidence interval, 190,000 to 260,000) in all 5558 such hospitals in 1990, including 163,000 persons presenting with conditions other than HIV or AIDS (95 percent confidence interval, 130,000 to 196,000). In 1990, in 593 U.S. hospitals with AIDS-diagnosis rates of 1.0 or more per 1000 discharges, HIV testing of patients 15 to 54 years old (3 million patients, or 12.0 percent of all patients in U.S. acute care hospitals) would have identified an estimated 68 percent of all HIV-positive patients (110,000 patients) who were admitted with conditions other than symptomatic HIV infection or AIDS. CONCLUSIONS We estimate that about 225,000 HIV-positive persons were hospitalized in 1990, of whom only one third were admitted for symptomatic HIV infection or AIDS. Routine, voluntary HIV testing of patients 15 to 54 years old in hospitals with 1 or more patients with newly diagnosed AIDS per 1000 discharges per year could potentially have identified as many as 110,000 patients with HIV infection that was previously unrecognized.

The macaque monkey infected with simian immunodeficiency virus (SIV) is an animal model of the acquired immunodeficiency syndrome. We investigated a laboratory worker who was exposed by needlestick accident to blood from an SIV-infected macaque. Seroreactivity to SIV developed within 3 months of exposure, with antibody titres peaking from the third to the fifth month and declining thereafter. Polymerase chain reaction for SIV sequences and cultures of peripheral-blood mononuclear cells failed to show infection. Inoculation of an SIV-negative monkey with blood from the worker did not cause infection. Animal-care and laboratory workers should adhere strictly to recommended procedures to avoid accidental exposures when working with SIV-infected animals or specimens.

A network of surveys of HIV seroprevalence in American Indians and Alaska Natives (AI/AN) was begun in 1989. From July 1, 1989 through June 30, 1991, 37,681 serologic specimens were collected from prenatal and sexually transmitted disease patients in 58 facilities operated or funded by the Indian Health Service. Specimens from AI/AN women receiving initial prenatal care showed an overall HIV prevalence of 0.3/1,000, while specimens obtained during the third trimester of pregnancy showed an overall prevalence of 1.0/1,000. The rate for rural third trimester prenatal patients (0.9/1,000) was similar to that for urban patients (1.1/1,000). HIV rates among third trimester AI/AN patients in three western states were 4 to 8 times higher than rates observed in childbearing women of all races in those states. The overall HIV seroprevalence in AI/AN seeking care for sexually transmitted diseases was 4.5/1,000 for males (urban 10.8/1,000; rural 2.0/1,000) and 0.7/1,000 for females (urban 0.9/1,000; rural 0.6/1,000). Approximately 1,210 to 4,250 (midpoint of range = 2,730) AI/AN in the U.S. are projected from survey findings to be currently infected with HIV. The presence of HIV in multiple specimens from rural areas and the similarity of HIV infection rates for female patients from rural and urban locations provides evidence of diffusion of the HIV epidemic to rural AI/AN, and emphasizes the need for effective HIV prevention for this population.

BACKGROUNDSince 1985, donors of organs or tissues for transplantation in the United States have been screened for human immunodeficiency virus type 1 (HIV-1), and more than 60,000 organs and 1 million tissues have been transplanted. We describe a case of transmission of HIV-1 by transplantation of organs and tissues procured between the time the donor became infected and the appearance of antibodies. The donor was a 22-year-old man who died 32 hours after a gunshot wound; he had no known risk factors for HIV-1 infection and was seronegative.METHODSWe reviewed the processing and distribution of all the transplanted organs and tissues, reviewed the medical histories of the donor and HIV-1-infected recipients, tested stored donor lymphocytes for HIV-1 by viral culture and the polymerase chain reaction, and tested stored serum samples from four organ recipients for HIV-1 antigen and antibody.RESULTSHIV-1 was detected in cultured lymphocytes from the donor. Of 58 tissues and organs obtained from the donor, 52 could be accounted for by the hospitals that received them. Of the 48 identified recipients, 41 were tested for HIV-1 antibody. All four recipients of organs and all three recipients of unprocessed fresh-frozen bone were infected with HIV-1. However, 34 recipients of other tissues--2 receiving corneas, 3 receiving lyophilized soft tissue, 25 receiving ethanol-treated bone, 3 receiving dura mater treated with gamma radiation, and 1 receiving marrow-evacuated, fresh-frozen bone--tested negative for HIV-1 antibody. Despite immunosuppressive chemotherapy, HIV-1 antibody appeared between 26 and 54 days after transplantation in the three organ recipients who survived more than four weeks.CONCLUSIONSAlthough rare, transmission of HIV-1 by seronegative organ and tissue donors can occur. Improvements in the methods used to screen donors for HIV-1, advances in techniques of virus inactivation, prompt reporting of HIV infection in recipients, and accurate accounting of distributed allografts would help to reduce further this already exceedingly low risk.

Interpretation of human immunodeficiency virus (HIV) antibody results that are "indeterminate" rather than clearly positive or negative is problematic for the person delivering the result as well as for the individual being tested. To improve counseling messages for these individuals, we evaluated data collected from a well-characterized cohort of 387 blood donors who had been monitored for up to 2 years. We sought to determine if persons with indeterminate Western blot patterns were infected with HIV, and whether information derived from follow-up monitoring would assist in the development of counseling messages for persons on whom no follow-up information was available. Donors were studied by laboratory assays, clinical evaluation, and assessment of risk for HIV. The absence of HIV infection in 97 of 98 donors with indeterminate Western blot patterns was confirmed by clinical follow-up, Western blot assays of sequential samples, and negative gene amplification results. We propose supplemental guidelines to be used as an adjunct to existing interpretive criteria for counseling individuals when they first present with an indeterminate Western blot finding.

To investigate the effect of human immunodeficiency virus type 1 (HIV-1) infection on subsequent hepatitis B virus (HBV) infection, HIV antibody was sought in homosexual men who developed HBV infection during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-1-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBV infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk of HBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%-80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-1-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers.

HIV-2 is endemic in West Africa but rare elsewhere. In the USA there have been 18 reported cases of HIV-2 infection; most identified people have been West Africans. We recently diagnosed the first case of HIV-2 infection in a native-born US citizen, a woman whose serum was found to be reactive to anti-HIV-1 enzyme immunoassay (EIA) when she attempted to donate blood in 1986. Although both HIV-1- and HIV-2-specific EIAs were reactive, the anti-HIV-2 Western blot (WB) was positive, while the anti-HIV-1 WB was positive or indeterminate on different occasions. Synthetic peptide testing was reactive for HIV-2 but not HIV-1. HIV-2 DNA was detected using the polymerase chain reaction procedure. Although she had travelled to West Africa, it is unclear how she became infected with HIV-2.