Seroepidemiology of HTLV-III (LAV) in the Federal Republic of Germany

Summary In 1984 10,281 sera were collected in the FRG and examined for antibodies to HTLV-III (LAV) with an enzyme-linked immunosorbent assay and confirmative tests. Of the German AIDS patients 81% have antibodies. Individuals belonging to AIDS risk groups, homosexuals, haemophiliacs and i.v. drug abusers, have antibody frequencies between 25%–72%. The detection of HTLV-III antibodies in blood donours indicates that the virus is being transmitted by blood transfusions.Abbreviations AIDS acquired immunodeficiency syndrome - LAS lymphadenopathy syndrome - ARC AIDS related complex - LAV lymphadenopathy associated virus - HTLV-III human T-lymphotropic virus type III - HBV hepatitis B virus     

Time relationship of immune changes to HTLV-III/LAV seroconversion in patients with hemophilia

Longitudinal immune studies of patients with hemophilia A were begun in 1982 by the Regional Hemophilia Center in St. Louis, Missouri. Serum samples collected from 74 participants between 1982 and 1985 were analyzed for antibody to human T-lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV). The incidence of antibody to HTLV-III/LAV has increased significantly in this population of patients with hemophilia. Only one of eight hemophiliacs had detectable antibody before July 1982, whereas 88.7% (55/62) were positive in 1985. T-cell surface markers were markedly abnormal in seropositive hemophilia patients with decreased percentage and number of OKT4-positive cells compared with seronegative hemophiliacs and controls. Lymphoproliferative responses to mitogens and antigens were normal in seronegative hemophilia patients. Seropositive hemophiliacs, compared with seronegative hemophiliacs, had significantly decreased lymphoproliferative responses, especially to pokeweed mitogen, tetanus, and Candida stimulations. Immune studies of seven HTLV-III/LAV seropositive hemophiliacs revealed antigen unresponsiveness and decreased T4 cells 2 to 32 months prior to development of full-blown AIDS. Longitudinal immune studies from 1983-85 revealed increasing number of seropositive hemophiliacs with antigen unresponsiveness and decreased T4 cells.     

Prevalence of HIV antibodies in groups at risk in Zürich,Switzerland

Summary The prevalence of HIV antibodies in various groups at risk was studied in 1,546 persons in Zürich. The prevalence was 17% (39/236) in homosexual men, 7% (13/180) in bisexual men, and 45% (14/31) and 42% (22/53) in female and male intranvenous drug abusers, respectively. Heterosexual transmission appeared to be the route of infection in four seropositive persons (two women and two men) who had no homosexual contacts and were not drug abusers (4/1050).Abbreviations HIV Human immune deficiency virus - HTLV III Human T-cell lymphotropic virus type III - IVDA Intravenous drug abusers - LAV Lymphadenopathy-associated virus     

Prevalence of HIV antibodies among prostitutes in Zürich,Switzerland

Summary The prevalence of antibodies to the human immune deficiency virus was determined in 123 prostitutes. Of 18 intravenous drug abusers 14 were anti-HIV positive, all others, with one exception, were seronegative. Neither race, nor number of clients, nor sexual practices correlated with seropositivity.Abkürzungsverzeichnis HIV Human immune deficiency virus - HTLV III Humans T-cell lymphotropic virus type III - LAV Lymphadenopathy-associated virus     

False-Positive Tests for Syphilis Associated with Human Immunodeficiency Virus and Hepatitis B Virus Infection among Intravenous Drug Abusers

 The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76–2.83] was observed for HIV-seropositive intravenous drug abusers; biological false-positive reactions were also more frequent (OR 1.73, 95% CI 1.30–2.31) among intravenous drug abusers who were hepatitis B virus seropositive but not among those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48–1.69). Among homosexuals, the association between HIV and biological false-positive reactions was restricted to subjects who were also intravenous drug abusers, indicating the crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers with a previous biological false-positive reaction yielded a false-positive result in their subsequent visit.     

The LAV/HTLV-III virus may evade elimination by the immune system by inducing low zone tolerance to itself

The acquired immunodeficiency syndrome (AIDS) is caused by the LAV/HTLV-III virus. The incubation period for AIDS is prolonged and on the order of years. We hypothesize that during this prolonged incubation period the LAV/HTLV-III virus is replicating very slowly and is present in extremely low concentrations. The concentrations of the virus may be low enough that the virus induces a low zone tolerance to itself in the T-cell arm of the immune system. B-cells which are resistant to direct low dose tolerance induction may remain responsive to the LAV/HTLV-III virus in a direct fashion without specific helper T-cells. Thus, anti-LAV/HTLV-III antibody may be produced even though the more important cellular immune response has been crippled by the virus. We also outline two hypothetical approaches for breaking this tolerance and restoring the cellular immune response to the LAV/HTLV-III virus.     

Human immunodeficiency virus (HIV) seropositivity in intravenous (i.v.) drug abusers in three cities of Italy: possible natural history of HIV infection in i.v. drug addicts in Italy

The prevalence of human immunodeficiency virus (HIV) antibodies and the symptoms induced [persistent generalized lymphadenopathy (PGL), AIDS-related complex (ARC), acquired immunodeficiency syndrome (AIDS)] was evaluated in several groups of intravenous (IV) drug abusers in three large Italian cities (Milan, Bologna, and Rome). The earliest evidence of seropositivity in sera collected from patients with acute viral hepatitis dates back to 1979 in Milan and to 1981 in Bologna with peaks in 1983 in both cities. In two groups of IV drug addicts on methadone-maintenance treatment at assistance centers, the prevalence of seropositivity differed sharply between Rome (33.3%) and Milan (69.3%) in 1985. Rates of seroconversion were also found to be higher in Milan than in Bologna and Rome. When a population of IV drug abusers voluntarily attending centers for surveillance of AIDS and/or ARC were investigated, high levels (range 55.2-81.5%) of seropositivity were found in the three cities. ARC prevalence among seropositives was very high (range 48.1-64.2% in 1985) in the three cities. The evolution rate to AIDS in Milan was higher among those attending a center for AIDS surveillance (7.4%) than among those attending an assistance center for methadone treatment (0.9%). These data are compatible with the hypothesis that virus infection among IV drug abusers originated in and then spread widely in Northern Italy (Milan first and then Bologna). Both the first appearance and subsequent spread of virus infection are in keeping with the reported occurrence of AIDS cases in the corresponding three regions of Milan, Bologna, and Rome.     

Occupational risk of the acquired immunodeficiency syndrome among health care workers

In August 1983, we initiated nationwide prospective surveillance of health care workers with documented parenteral or mucous-membrane exposures to blood or other body fluids of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related illnesses. The purpose of the surveillance project is to quantitate prospectively the risk to health care workers of acquiring the AIDS virus, human T-cell lymphotropic virus Type III/lymphadenopathy-associated virus (HTLV-III/LAV), as a result of occupational exposures. By December 31, 1985, 938 health care workers were being followed in the surveillance project. The mean length of follow-up was 15 months (range, 0 to 56) and 531 health care workers (57 percent) had been followed for more than one year. Needlestick injuries and cuts with sharp instruments accounted for 76 percent of the exposures. Over 85 percent of all exposures were to blood or serum. None of the health care workers have acquired signs or symptoms of AIDS. Analyses of T-lymphocyte subsets were performed for 341 (36 percent) of the exposed health care workers, and tests for antibody to HTLV-III/LAV were performed for 451 (48 percent). Seven health care workers who had low helper/suppressor T-lymphocyte ratios on initial testing were retested; only three had persistently low ratios. Only two health care workers tested were seropositive for antibody to HTLV-III/LAV. The results of this surveillance project, thus far, suggest that the risk to health care workers of occupational transmission of HTLV-III/LAV is low (the upper bound of the 95 percent confidence interval for the seroprevalence rate among workers with greater than or equal to 3 months of follow-up with HTLV-III/LAV antibody testing is 1.65 percent) and appears to be related to parenteral exposure to blood.     

HIV infection in intravenous drug abusers in Berlin: Risk factors and time trends

Summary To investigate the epidemiology of HIV infection among intravenous drug abusers (IVDA) in Berlin (West), from October 1984 to October 1988, 741 heterosexual IVDA were recruited from facilities for drug treatment and counseling. In this group 22.8% were seropositive for antibodies against HIV, representing 21.1% of the females and 23.5% of the males. Seroprevalences of hepatitis B, hepatitis A, and lues were 67.7%, 40.1%, and 4.0%, respectively. Seropositivity for HIV antibodies correlated with positive seromarkers for hepatitis B and A, and with certain behavioral and social features such as sharing of injection equipment, imprisonment, and intravenous drug use in prison. The crude time trend of HIV seroprevalence shows an increase from 17.1% in those subjects who discontinued i.v. drug abuse in 1983 or earlier to 31.5% in 1985, and a decrease over the past 3 years to 14.1% in 1988. After adjusting for temporary changes in the study group, the estimated HIV seroprevalence odds show an almost steady increase and were significantly higher for those who were injecting drugs in 1987 and 1988 compared with those who stopped i.v. drug use before 1984. Thus IVDA with a persistent risk profile are at a still-increasing risk of acquiring HIV infection.Abbreviations AIDS acquired immunodeficiency syndrome - CDC centers for disease control - HIV human immunodeficiency virus - IVDA intravenous drug abusers - PGL persistent generalized lymphadenopathy     

Hepatitis B and D virus infection among drug abusers in Taiwan

Approximately 15 to 20% of the general population in Taiwan are chronic hepatitis B surface antigen (HBsAg) carriers. However, the incidence of hepatitis D virus (HDV) infection is low (5-8%) in patients with HBsAg-positive chronic liver diseases in this area. To evaluate the prevalence of hepatitis B virus (HBV) and HDV infection among drug abusers in Taiwan, serum samples were collected from 152 drug abusers at the Taipei Municipal Anti-Narcotic Institute and test for HBV and HDV markers. Of these, 24 (15.8%) were HBsAg positive, and only 15 (9.9%) were seronegative for all HBV markers. Of the 115 intravenous drug abusers, serum antibody to hepatitis D antigen (anti-HD) was positive in 78.9% of 19 persons who were HBsAg positive, and in 7.5% of 80 persons who were positive for antibody to HBsAg (anti-HBs). Anti-HD was not detected in the sera from all 37 nonintravenous drug abusers regardless of the status of their HBV markers. Also, none of 63 asymptomatic HBsAg carrier pregnant women or 23 patients with acute type B viral hepatitis had measurable anti-HD in their sera. Thus, the high frequency of HDV detected among Chinese HBsAg carrier intravenous drug abusers in Taiwan is similar to that reported in Western countries.     

Acute glandular fever-like illness in a patient with HTLV-III antibody

A lymph node biopsy obtained from a patient with human T-cell lymphocytotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody, presenting with an acute glandular fever-like illness, was examined by electron microscopy. Numerous pathological changes were present in the biopsy, including hypertrophy of smooth endoplasmic reticulum, intracytoplasmic rod-like inclusions within the cisternae of endoplasmic reticulum, multivesicular bodies, test-tube and ring-shaped forms, and tubulo-reticular structures. Intranuclear and intracytoplasmic viral-like particles measuring 105-120 nm in diameter and small cytoplasmic particles measuring 50-70 nm in diameter were found in some degenerating lymph node cells. These pathological findings may reflect a host cell response to various pathological and viral stimuli resulting from immune deficiency owing to infection with HTLV-III/LAV.     

T lymphocyte subsets and viral infections in Sardinian parenteral drug abusers: relationship to HIV infection

To investigate whether the human immunodeficiency virus (HIV) infection or the abuse of narcotic drugs or other viral infections may be responsible for immunologic abnormalities in parenteral drug abusers, sera from 168 consecutive individual patients were collected from 1985 to 1986. The sera were tested for antibody to HIV (anti-HIV), and the clinical, immunologic, and serologic characteristics of 83 seropositive and 53 seronegative parenteral drug abusers were compared. The presence of anti-HIV was significantly associated with a decreased number of T helper lymphocytes (P less than .001), a reduced T helper/suppressor ratio (P less than .001). Of the 83 seropositive patients, 63 (76%) had generalized lymphadenopathy and 16 (18%) had AIDS-related complex. No patient had AIDS. Parenteral drug abusers with AIDS-related complex had significant reductions in the number of T helper cells (P less than .01) and the T helper/suppressor ratio (P less than .01) compared with patients with lymphadenopathy syndrome (LAS), suggesting that parenteral drug abusers with HIV infection develop a progressive immunodeficiency. IgG antibody to cytomegalovirus was found in 75% of anti-HIV-positive and 45% of anti-HIV-negative parenteral drug abusers (P less than .01), but significant associations between anti-HIV and markers for other viruses were not found. Our data confirm that HIV infection is the major cause of low T helper cells and reversed T helper/suppressor ratio in parenteral drug abusers.(ABSTRACT TRUNCATED AT 250 WORDS)     

The AIDS epidemic

This article reviews the magnitude of human T-lymphotropic virus type III (HTLV-III) exposure, the outcome of such exposure, the economic burden of HTLV-III-related disease, and the social, ethical and public implications of the acquired immunodeficiency syndrome (AIDS) epidemic. The ELISA serum antibody test for HTLV-III is useful for diagnostic purposes, but does not indicate whether the person currently harbors the virus. Additional studies are needed to demonstrate that there are not antibodies to other viruses that cross-react in the test. Seropositivity from lymphadenopathy-associated virus (LAV) rose from under 10% in 1978 to 49% in 1984 among homosexual men attending a Colorado clinic for sexually transmitted diseases. In San Francisco, the prevalence of HTLV-III antibodies among homosexual men attending another such clinic reached 65% in 1984. Parenteral drug users have demonstrated similar increases in seropositity rates. The total number of persons in the US who are positive for HTLV_III antibodies is estimated to be at least 400,000 persons. Initial study results suggest that 4-19% of these seropositive individuals develop full-blown AIDS in 1-5 years. 40,000 new cases of AIDS are expected in the next 2 years. The AIDS epidemic has severely stressed the US health care system in terrms of its financial costs, use of resources, and effect on medical personnel. It is not unreasonable to estimate that AIDS will cost US society over half a billion dollars during the next calendar year. The grat social and economic burden associated with AIDS, and the effects of a positive ELISA test upon those tested, create a multitude of concerns. There is a need for a national coordinated health program on AIDS, as well as for special measures such as a national catastrophic fund for HTLV-III-related disease. Finally, the threasts to confidentiality posed by licensure of the HTLV-III antibody test must be recongnized.     

Human immunodeficiency virus infection in a Dublin general practice.

A group general practice in Dublin's inner city has had extensive experience of intravenous drug users since the late 1970s. Since 1985 a total of 54 human immunodeficiency virus (HIV) seropositive patients have attended the practice, of whom 48 are intravenous drug users, four are the children of drug users and two have been infected through sexual contacts. Three patients have developed the acquired immune deficiency syndrome and at least eight have symptomatic HIV disease. Sixty per cent of Ireland's seropositive population have been infected through intravenous drug abuse but nationally only 16% of all intravenous drug users tested are seropositive; in the study practice, however, at least 35% (48/137) of known intravenous drug users are seropositive.     

Close relationships between neopterin and beta-2-microglobulin levels in intravenous drug abusers

Serum from 36 intravenous drug abusers without acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were tested for concentrations of neopterin and beta 2-microglobulin. The seroprevalence of human immunodeficiency virus (HIV) antibody in this group was 50%. Previous studies of this group showed that the HIV antibody positive patients had significant increases in HLA-DR expression on peripheral blood lymphocytes and increases in serum soluble CD8 antigen. Both neopterin and beta 2-microglobulin concentrations were significantly higher in the HIV antibody seropositive patients compared to the seronegative patients (p = 0.001 and p = 0.005, respectively). A highly significant positive correlation between neopterin and beta 2-microglobulin was found for the seropositive patients (r = 0.8879, p less than 0.0001) as well as for the entire group (r = 0.6054, p = 0.0002). Significant positive correlations were also found between neopterin or beta 2-microglobulin and the percent DR + T cells and CD8 antigen levels, although these correlations were not as significant as that observed between neopterin and beta 2-microglobulin. No relationships were found between neopterin or beta 2-microglobulin and total CD4 cell concentrations or CD4/CD8 ratios. These data demonstrate the significant interrelationships between various immune activation markers in a population at risk for developing AIDS.     

Immunologic abnormalities related to antigenaemia during HIV-1 infection.

The expression of phenotypic markers on T and B lymphocytes in long-term human immunodeficiency virus type 1 (HIV-1) seropositive, antigen negative patients, in seropositive, antigen positive individuals without AIDS and in seronegative intravenous drug abusers was examined by two colour flow cytometry. Seropositive, antigen positive patients showed decreased CD4+ lymphocyte numbers, causing lower CD4/CD8 ratios when compared to seropositive, antigen negative subjects. While CD4 CDw29+ (4B4) lymphocytes are selectively reduced in seropositive, antigen negative individuals, both CD4 CDw29+ and CD4 CD45R+ (2H4) lymphocytes are decreased when antigenaemia is present. An increased percentage of CD3 HLA DR+ activated T lymphocytes and of CD20+ (B1) Leu 8 negative activated B cells was seen in HIV-1 seropositive antigen positive patients. These results demonstrate that, in long-term seropositive individuals, antigenaemia is associated with peculiar phenotypic changes of lymphocyte subsets.     

Glycosylation pattern of herpes simplex virus type 2 glycoprotein G from precursor species to the mature form

Summary Studies of adult T-cell leukaemia virus/human T-cell leukaemia/lymphotropic viruses (ATLV/HTLV-I) in Japan indicate that the virus is involved only with the development of ATL. By contrast, reports from the U.S.A. about HTLV have from time to time claimed that related HTLV are concerned not only with ATL of black persons, but also with a wide range of diseases, such as mycosis fungoides/Sezary's syndrome, T-cell hairy cell leukaemia, acquired immune deficiency syndrome (AIDS) and also multiple sclerosis. Using morphological, biological, serological and molecular hybridisation studies, we were able to confirm that the viruses implicated in the development of ATL and AIDS are distinct and that ATLV/HTLV-I is involved only in ATL, and HIV/LAV/HTLV-III only in AIDS. In vitro, ATLV/HTLV-I transformed and immortalised T-cells, while HIV/LAV/HTLV-III killed our T-cells. Failure to detect any serological cross-reaction indicates that all the structural proteins are different. Likewise, Southern blot studies failed to reveal any cross-hybridisation. Sixty patients with multiple sclerosis failed to reveal any association with ATLV/HTLV-I or with HIV/LAV/HTLV-III. Our conclusion is that ATLV/HTLV-I is involved only in ATL of Japanese and of some black persons of African origin, and that HIV/LAV/HTLV-III is associated only in AIDS.     

Hepatitis D virus infection among intravenous drug abusers in Taiwan: analysis of risk factors and liver function tests

To investigate the prevalence of hepatitis D virus (HDV) and hepatitis B virus (HBV) infection among intravenous drug abusers in Taiwan, a total of 761 male prisoners, including 680 intravenous drug abusers, were studied for serological markers of HBV and HDV. Questionnaires were distributed to evaluate the risk factors for HDV infection and also to estimate the strength of association among HDV infection and the risk factors. HBV infection was common, and the positive rates of HBV markers between intravenous drug abusers and non-drug abusers were not statistically different. However, the positive rate of the antibody to HDV was significantly higher among intravenous drug abusers than among non-drug abusers (21.3% vs. 8.6%). Of 131 chronic HBV carriers with intravenous drug abuse, 119 (91%) were anti-HD positive. Using multiple logistic regression models, we found that the most important risk factor for HDV infection was hepatitis B surface antigen (HBsAg) carriage, and intravenous drug addiction the next. A matched case-control study also was conducted to compare liver function tests among both anti-HD- and HBsAg-positive group anti-HD-negative, and HBs-AG-positive group as well as those with neither positive. Statistically significant difference in liver function tests was not found. It is concluded that the HBsAg carriers with intravenous drug abuse in Taiwan are commonly HDV infected with and that the infection does not seem to affect the liver as assessed by liver function tests.     

Detection of HTLV-III/LAV antigens in peripheral blood lymphocytes from patients with AIDS

Summary HTLV-III was searched for in frozen sections of peripheral blood lymphocytes obtained from AIDS patients by an immunofluorescence technique. Human IgG against HTLV-III/LAV and monoclonal antibodies against HTLV-III/LAV P24 antigen, yielded a strong cytoplasmic fluorescence in frozen sections of the lymphocytes. Some cells containing HTLV-III antigens displayed multinucleated giant forms. They also reacted with monoclonal antibodies against helper/inducer T-cells (OKT 4⁺), as demonstrated by direct double staining immunofluorescence. Similarly, complexes of immunoglobulins and C₃ component of complement were also detected on HTLV-III/LAV Ag expressing lymphocytes.Immunofluorescence study of frozen sections of peripheral blood lymphocytes appeared to be a simple, fast and reliable method for detection of HTLV-III/LAV Ag in AIDS patients.With 3 Figures