Human T-cell Lymphotropic Virus Type III Antibody Research Articles

Clinical investigations of lymphadenopathy, including lymph node biopsies, in 24 homosexual men with antibodies to the human T-cell lymphotropic virus type III (HTLV-III).

The findings of 27 lymph node biopsies performed on 24 homosexual patients with lymphadenopathy are presented. Six had acquired immune deficiency syndrome (AIDS) and 18 lymphadenopathy only, of whom one subsequently developed AIDS. All these patients had antibodies to the human T-cell lymphotropic virus type III (HTLV-III) suggesting that HTLV-III is currently the commonest cause of lymphadenopathy in homosexual men. The histopathological findings of six of seven nodes from AIDS patients showed either follicular depletion alone or follicular and paracortical lymphocyte depletion. Nodes from four patients showed Kaposi's sarcoma, three of which also showed follicular hyperplasia. In two of these patients there were no cutaneous manifestations of this condition. One lymph node from a patient with persistent generalized lymphadenopathy (PGL) showed Mycobacterium tuberculosis. Six nodes from six other patients have had features of toxoplasmosis although there was no serological or clinical evidence of recent toxoplasma infection. The remaining 11 lymph nodes from patients with PGL and one node from a patient with transient lymphadenopathy, showed reactive follicular hyperplasia only. We conclude that homosexuals with lymphadenopathy who are HTLV-III antibody positive do not need a routine node biopsy unless an alternative diagnosis is strongly suspected.

Neurologic disease as the presenting manifestation of acquired immunodeficiency syndrome.

Neurologic disease was the harbinger of the acquired immunodeficiency syndrome (AIDS) in 26 (20%) of 132 patients and ultimately developed in 83 (63%). The most common neurologic disorder heralding AIDS was toxoplasmic encephalitis (17 cases) followed by cryptococcal meningitis (six), retinitis (three), progressive multifocal leukoencephalopathy (two), neuropathy (one), myopathy (one), and subacute "viral" encephalitis (one). In four patients, more than one neurologic disorder coexisted at presentation. Recognition of underlying human T cell lymphotropic virus type III (HTLV-III) infection may allow a more expedient determination of the cause of the neurologic disease. Our study emphasizes the importance of testing for the presence of HTLV-III antibody and assessing the immunologic status of all patients at risk for AIDS who have neurologic illness.

HTLV-III Antibodies After Immune Globulin

To the Editor.— In their recent letter, Wolfe et al 1 presented an analysis of the potential of a transient false-positive reaction on an enzyme-linked immunosorbent assay for antibody to human T-cell lymphotropic virus type III (HTLV-III) in recipients of immune globulin (IG) made from unscreened source material. Their analysis was limited to the case of intramuscular administration of a 5-mL dose of IG to US military personnel. Two factors not included in the case analyzed by Wolfe et al can greatly increase the chance of observing a transient false-positive in the HTLV-III antibody test. The standard dose in the case presented by these authors, calculated on the basis of their assumptions, is 10 mg/kg. Intravenous (IV) IG therapy is often given at a dosage of 400 mg/kg. Consequently, a recipient of IV IG may have a serum titer of passively received antibodies that is 40 times greater than that

More on HTLV-III Antibodies in Immune Globulin

<h3>To the Editor.—</h3> Recently, concern has been raised about the passive transmission of human T-cell lymphotropic virus type III (HTLV-III) antibodies during immune globulin (IG) administration.¹Some contend that these antibodies could cause a transient "false-positive" reaction on enzyme-linked immunosorbent assay (ELISA) screening tests for the HTLV-III antibody. The military services administer IG to large numbers of personnel on active duty and also screen all military personnel for evidence of HTLV-III antibodies. Any transient positive screening results caused by the administration of IG would, therefore, have a significant impact on the military program. White et al²indicated that hypogammaglobulinemic patients demonstrated increased HTLV-III antibody absorbance values following infusion of IG. However, these increases were not great enough to exceed the cutoff range of positivity. Such results are not surprising when one considers the dilution involved. We conducted a serological study, using ELISA methodology, to assess the effect of

HTLV-III Antibodies in Drug-Addicted Prostitutes Used by US Soldiers in Italy

To the Editor.— The controversial issue of the human T-cell lymphotropic virus type III (HTLV-III) infection rate among US soldiers in Berlin and its relationship with use of prostitutes,1,2in particular intravenous drug abusers, prompted us to report our data from Italy. To study the relationship between HTLV-III infection and the development of malignant lymphoma, 315 intravenous drug abusers seen in five centers for drug addicts from three provinces (Pordenone, Udine, and Gorizia) of Friuli Venezia Giulia, a region of 1.5 million inhabitants close to the borders of Austria and Yugoslavia, were clinically examined. They were also given laboratory tests including an HTLV-III antibody test (enzyme-linked immunosorbent assay) and T4/T8 ratios and completed a questionnaire on their drug abuse and sexual behavior. Human T-cell lymphotropic virus type III antibodies were detected in 86 (27% ) of the overall population, and 65 intravenous drug abusers (21%) were affected by persistent generalized

Human T-Cell Lymphotropic Virus Type III Associated Disorders

Eleven heterosexual patients (nine women, two men) without classic risk factors for development of acquired immunodeficiency syndrome (AIDS) were seen between March 1983, and April 1985, and diagnosed as having AIDS (four), persistent, generalized lymphadenopathy (PGL) (four), or asymptomatic human T-cell lymphotropic virus type III (HTLV-III) carrier state (three). The clinical presentations and course of those with AIDS or PGL were similar to those reported in homosexual men with AIDS or PGL, with reversed T4/T8 ratio, and the presence of antibody to HTLV-III. Asymptomatic carriers had normal T4/T8 ratios, had an absence of HTLV-III antibodies, but had HTLV-III virus cultured from blood. We conclude that the heterosexual population, with or without history of sexual exposure to individuals at risk for AIDS, may develop a wide range of clinical manifestations secondary to HTLV-III, varying from AIDS to the asymptomatic carrier state.

False-Positive Western Blot Tests for Antibodies to HTLV-IIIN

To the Editor.— As part of the US Army quality assurance program for human T-cell lymphotropic virus type III (HTLV-III) testing, we recently sent identical proficiency panels to five large commercial firms that offered HTLV-III Western blot testing on a fee-for-service basis. Each panel consisted of 15 samples from healthy, low-risk adults whose serum was repeatedly negative for HTLV-III antibodies and five samples from HTLVIII-infected (culture-documented) patients. By Western blot analysis, all five positive samples produced definite, but not strong, bands at 41 kilodaltons (kd) and other molecular weights characteristic of HTLV-III proteins. 1 Scores ranged from 85% to 100% accuracy (Table). Four of the five laboratories reported at least one falsepositive test result. The six falsepositive results were all on different normal specimens, suggesting that the errors were due to technique and not to intrinsic biologic properties of the specimens. There was a substantial range of clarity of the

HTLV-III Antibody Testing in Hong Kong

To the Editor.— Hong Kong's current population is estimated at 5.4 million; about 90% are ethnic Chinese. It has a thriving tourist industry, with about 17 million arrivals and departures in 1984. Homosexual practice is illegal. Virtually no information regarding the number and sexual behavior of the homosexuals in this city is available. Prostitution is also illegal, although the service of prostitutes is readily obtainable in certain districts. Just how rigorously laws governing homosexualityand prostitution are enforced is not known. Because of the extensive exchange of visitors between Hong Kong and countries with high prevalence of acquired immunodeficiency syndrome (AIDS), human T-cell lymphotropic virus type III (HTLV-III) infections would be expected to be present in Hong Kong. We have therefore initiated a study to assess the frequency of HTLV-III antibodies among residents of this city. Study.— Ten groups of subjects were tested (Table). All serum samples were collected in

Detection of human T-cell lymphotropic virus type III-related antigens and anti-human T-cell lymphotropic virus type III antibodies by anticomplementary immunofluorescence

Techniques presently available for detection of human T-cell lymphotropic virus type III (HTLV-III) antigens and antibodies are laborious or relatively nonsensitive. We adapted anticomplementary immunofluorescence (ACIF) for these purposes. In HTLV-III-infected cells, specific ACIF was demonstrated by a diffuse speckling pattern that often resulted in a peripheral cellular rim of fluorescence. A 97% concordance was demonstrated between the ACIF assay and other sensitive tests for HTLV-III antibody detection (Western blot and membrane immunofluorescence and fixed-cell immunofluorescence tests). The ACIF assay was both more sensitive and more specific when compared with the enzyme-linked immunosorbent assay. For detection of HTLV-III antigens, the ACIF assay appeared to be as sensitive as the reverse transcriptase assay and more sensitive, with less background reactivity, than the conventional immunofluorescence assay. The ACIF assay often detected low levels of HTLV-III antigens within 3 days of infection in vitro, compared with 5 to 7 days with the indirect immunofluorescence assay, and generally paralleled the reverse transcriptase assay. The ACIF assay is a simple, sensitive, and specific assay for detection of HTLV-III-related antigens and antibodies. It should prove useful in the diagnosis of HTLV-III infection, as well as in studies of pathogenesis.

AIDS, Blood Transfusions, and Directed Donations

Prince et al. (Feb. 6 issue) recently expressed concern that human T-cell lymphotropic virus Type III (HTLV-III) could be transmitted by intravenous immune globulin preparations. They suggested that conditions used to make intermediate Cohn-Oncley fractions did not inactivate spiked HTLV-III; however they did not study partitioning of HTLV-III into the various fractions. We recently reported the results of such studies. HTLV-III was spiked into the various Cohn-Oncley fractions and its partitioning between precipitates and supernatants as well as inactivation was studied by viral cultures and quantitative antigen measurements by antigen-capture enzyme-linked immunosorbent assay (ELISA). These studies showed that HTLV-III was partioned and inactivated at multiple steps in the Cohn-Oncley process. At the most efficient step HTLV-III was quantitatively (99.5%) partitioned into precipitate III a fraction discarded during the manufacturer of immune globulin. The cumulative effects of partitioning and inactivation resulted in a potential efficiency of virus removal of 10(15) infectious units per milliliter. This efficiency is many orders of magnitude greater than would be needed to eliminate the small amounts of virus that potentially could be present in plasma pools used for immune globulin manufacture. Thus the conjecture of Prince et al. that lyophilization of immune globulin would preserve HTLV-III infectivity is not relevant. In addition not all intravenous preparations are lyophilized as they implied. Surveillance studies of recipients of intravenous immune globulin suggested by Prince et al. have been under way since the autumn of 1985. The number of patients is limited because most recipients are immunodeficient and would not be expected to acquire antibodies even if they were infected with HTLV-III. Furthermore because immune globulin preparations may contain antibodies to HTLV-III patients receiving immune globulin on a long-term basis are unsuitable for study; antibody detected in serum samples from such patients could have been transferred passively. Despite these limitations 134 recipients (mostly patients with immune thrombocytopenia but a few with renal transplants or Kawasakis disease) of intravenous immune globulin made by various manufacturers (data provided by J. Bussel M.D. The New York Hospital-Cornell Medical Center The Massachusetts Public Health Biologic Laboratories Miles Laboratories Travenol Laboratories The Blood Transfusion Service of The Swiss Red Cross Immuno AG and Kabi Vitrum AB) have been followed for 2 to 24 months by means of ELISA and Western blotting of serum reactive by ELISA. 3 patients had passively transferred antibodies; none produced HTLV-III antibodies. Thus the results of laboratory studies of the fractionation process and surveillance of immune globulin recipients corroborate epidemiologic observations indicating that receipt of immune globulin is not associated with the risk of the development of AIDS. (full text)

Pyoderma Gangrenosum in a Patient With HTLV-III Antibody

To the Editor.— Pyoderma gangrenosum (PG) is an uncommon cutaneous ulcerative disease of unknown causes. 1 Human T-cell lymphotropic virus type III (HTLV-III) antibody has been isolated in individuals with acquired immunodeficiency syndrome (AIDS) or at risk for AIDS. 2 Both conditions have been associated with quantitative and qualitative abnormalities in humoral and cell-mediated immunity. We herein report a case in which the two conditions coexist. Report of a Case.— A 23-year-old homosexual man was examined at Dartmouth-Hitchcock Medical Center, Hanover, NH, in March 1985 for a six-year history of recurrent episodes of bilateral lower-extremity ulcers. The lesions have begun as inflammatory nodules or pustules, which rapidly enlarge and ulcerate. The tender ulcers have violaceous, undermined, raised borders with beefy exudative bases. The lesions are slow to heal, granulating over several months. Over the years, the patient has been treated with a variety of agents, including systemic and topical antibiotics,

HTLV-III Antibody in Intravenous Drug Abusers of Metropolitan Barcelona, Spain

To the Editor. —The presence of antibodies to human T-cell lymphotropic virus type III (HTLV-III) has been studied in patients affected by acquired immunodeficiency syndrome (AIDS), AIDS-related complex, lymphadenopathy syndrome, in symptom-free individuals at high risk of developing AIDS, and in the general population. The presence of antibodies to HTVL-III in intravenous drug abusers (IDAs) has been reported as showing great geographic differences, from 87% in the United States 5 to 1.5% in the United Kingdom. 3 In this letter, we report the preliminary results of a study of 92 consecutive heterosexual IDAs who were residents of metropolitan Barcelona, Spain, and admitted to our hospital because of infectious complications or for treatment of their drug addiction. All HTLV-III seropositive and sero-negative IDAs usually shared needles on more than one occasion. All patients were living in metropolitan Barcelona during their drug-abuse period. It is very improbable that they used needles from

Leukopenia and Anergy as Predictors of AIDS-Reply

<h3>In Reply.—</h3> Cohen and associates, in their accompanying letter, have collected WBC counts on more than 11,000 adult inmates of a division of the New York City jail and determined that approximately 2.5% were leukopenic. This is certainly consistent with our historical data.¹They have also determined that less than 10% of those who were leukopenic were also anergic. All 22 anergic inmates had a history of parenteral drug abuse. No data on human T-cell lymphotropic virus type III (HTLV-III) antibody appear to be available. Leukopenia, per se, does not seem to be predictive of anergy or other prodromal signs and symptoms associated with AIDS. The development of testing procedures for HTLV-III antibody permits identification of those who have been exposed to the virus associated with AIDS, of whom only a portion are either prodromal or overtly ill.²Antibodies against HTLV-I, HTLV-II, and HTLV-III are prevalent among intravenous

AIDS and Testing for AIDS

To the Editor.— In the recent article, Status Report on the Acquired Immunodeficiency Syndrome, the Council on Scientific Affairs 1 calculated that testing blood components for human T-cell lymphotropic virus type III (HTLV-III) using Abbott Laboratories' enzyme-linked immunosorbent assay kit would result in 20,000 positive results annually. This calculation assumed there are 20 million blood donors annually and a prevalence rate of HTLV-III antibody in the general population of 0.1%. Unfortunately, the number of donors (D) multiplied by the prevalence of the antibody (P) equals the number of persons with HTLV-III antibody, not the number of positive test results, as these authors concluded. The number of positive results in fact is the sum of the number of true-positives plus the number of false-positives. Standard probability theory 2 shows that true-positive equals D × P × sensitivity and false-positive equals D(1—P)(1—specificity). Thus, the expected number of positive results equals D × P

AIDS and Testing for AIDS

To the Editor.— The recent COUNCIL REPORT on human T-cell lymphotropic virus type III (HTLV-III) testing 1 provides important information on the meaning of the newly available serological tests for HTLV-III antibody and on information to be provided to individuals who have repeated positive test results. Since many of the readers of the report may have little or no experience with AIDS or HTLV-III testing, I believe that there are several clarifications of the recommendations that should be made. Public and private organizations are urged to advise high-risk individuals who have repeated positive results to establish a relationship with a physician trained in and experienced with signs and symptoms of AIDS and related disorders. It is essential that the same organizations be urged to ensure that individuals have access to such physicians. The recommendation regarding advising seropositive women about their offspring implies that any offspring is at increased risk of

AIDS virus infection in Nairobi prostitutes. Spread of the epidemic to East Africa.

The acquired immunodeficiency syndrome (AIDS) is epidemic in Central Africa. To determine the prevalence of AIDS virus infection in East Africa, we studied 90 female prostitutes, 40 men treated at a clinic for sexually transmitted diseases, and 42 medical personnel in Nairobi, Kenya. Antibody to human T-cell lymphotropic virus Type III (HTLV-III) was detected in the serum of 66 percent of prostitutes of low socioeconomic status, 31 percent of prostitutes of higher socioeconomic status, 8 percent of the clinic patients, and 2 percent of the medical personnel. The presence of the antibody was associated with both immunologic and clinical abnormalities. The mean T-cell helper/suppressor ratio was 0.92 in seropositive prostitutes and 1.82 in seronegative prostitutes (P less than 0.0001). Generalized lymphadenopathy was present in 54 percent of seropositive prostitutes and 10 percent of seronegative prostitutes (P less than 0.0001). No constitutional symptoms, opportunistic infections, or cases of Kaposi's sarcoma were present. Our results indicate that the epidemic of AIDS virus infection has, unfortunately, spread extensively among urban prostitutes in Nairobi, Kenya. Sexual exposure to men from Central Africa was significantly associated with HTLV-III antibody among prostitutes, suggesting transcontinental spread of the epidemic.

HTLV-III Antibody Testing: The False-Negative Rate

<h3>To the Editor.—</h3> During the last several months, much attention has been directed to the number of false-positive results of the test for human T-cell lymphotropic virus type III (HTLV-III) antibody.¹Concern has focused primarily on use of this test to screen blood donors and the worry that a large number of healthy donors would be falsely branded as HTLV-III viral carriers.²While this is an important and valid concern, some of this worry has already been dispelled.¹What remains largely unaddressed, however, is the number of false-negative results of the HTLV-III antibody test. There are now published case reports of individuals who are HTLV-III viral culture positive, but HTLV-III antibody negative.³The frequency of such cases is currently unknown. Such persons may be nonresponders to the specific inciting antigens or produce levels of antibody below the technical level of detectability. In addition, although there is

Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test.

The Abbott enzyme immunoassay (Abbott Laboratories, North Chicago, Ill.) for human T-cell lymphotropic virus type III (HTLV-III) antibody was evaluated to determine the effect of using heat-inactivated (56 degrees C for 30 min) serum as the sample. Each of 58 nonreactive serum samples gave a higher A492 value when tested after heat inactivation. Ten of the samples became reactive after heating. Heat-inactivated serum should not be used in the current Abbott HTLV-III antibody test, because this can cause false-positive results.

Insect-Borne Transmission of AIDS

To the Editor.— Although Dr Drotman 1 correctly downplays the current evidence for mosquito-borne transmission of the acquired immunodeficiency syndrome (AIDS) in the United States, I believe that several pieces of information suggest a possible role for insect-borne spread in the tropics. 2 That 50 of 75 serum samples collected from healthy children in the West Nile region of Uganda in 1973 had antibody to human T-cell lymphotropic virus type III (HTLV-III) 3 indicates that transmission is wide-spread and may occur early in life; either heterosexual or homosexual transmission with subsequent vertical transmission is unlikely to account for such high prevalence of infection. Therefore, in contrast to Dr Drotman's assertion, HTLV-III infection may be common in preadolescent children. In a small study of HTLV-III antibody in healthy Zairians, 22% were positive and 29% had borderline results; all were immunologically normal. 4 Even in the absence of follow-up data, it is reasonable

HTLV-III Infection Among Health Care Workers

Health care workers are caring for an increasing number of persons infected with human T-cell lymphotropic virus type III (HTLV-III), the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). We studied 361 health care and clinical laboratory personnel from institutions in several metropolitan areas with both high and moderate levels of HTLV-III infection among high-risk group members to evaluate routes of exposure to and seropositivity for HTLV-III. Protection of the privacy of subjects and prospective determination of risk factors were integral components of the study design. Six (26%) of 23 health care workers with recognized risk factors for AIDS had HTLV-III antibodies. Thirty-nine (14%) of 278 workers at one institution as well as a total of five workers from other institutions reported possible percutaneous exposure to HTLV-III, usually injuries with needles that had been used on AIDS patients. There were three HTLV-III seropositive subjects who reported possible parenteral exposure to HTLV-III but no recognized AIDS risk factors. One was a symptomatic female, subject A, and her apparent sources of HTLV-III exposure were two puncture wounds, without injection of blood, made with needles used on AIDS patients. Human T-cell lymphotropic virus type III was cultured from her asymptomatic, seronegative long-term sexual partner, apparently representing female-to-male transmission. For the two other seropositive workers (subjects B and C) with nosocomial parenteral exposure, we could not rule out heterosexual transmission as a possible source of HTLV-III exposure. These latter two cases as well as the identification of seropositive health care providers from known risk groups point to the need for thorough case investigation to identify routes of exposure in health care workers. The risk of nosocomial HTLV-III transmission appears to be low and related to percutaneous exposure. Medical personnel should be trained systematically in the proper techniques and handling of instruments for phlebotomy and similar procedures to decrease occupational exposure to HTLV-III.