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J J Goedert

Publications and source records attributed to J J Goedert.

At least 199 records · Page 11Linked to original sources

A method for predicting individual HIV infection status in the absence of clinical information.

Latent structure analysis can be used to determine sensitivity and specificity rates of human immunodeficiency virus antibody assays in the absence of previous clinical or laboratory results. The technique was applied to the analysis of data obtained when a panel of serum samples, collected as part of a large-scale screening project, were subjected to four conventional bioassays (ag121, p24, gp120, and an enzyme-linked immunosorbent assay). To determine the accuracy of this statistical approach, the results of latent structure analysis were compared with the known clinical diagnoses of patients from whom the samples were taken, and nearly 100% agreement was obtained. Although a two-class latent structure model had some predictive value, a three-class model more adequately explained assay patterns. The use of the four standard assays in conjunction with the statistical methods described here would largely reduce the need for confirmatory Western blot assays in analyses of large panels of samples.

AIDS Serodiagnosis↗

Spectrum of HIV-1 neutralizing antibodies in a cohort of homosexual men: results of a 6 year prospective study.

Serum samples collected prospectively between 1982 and 1987 from a cohort of homosexual men were analyzed for HIV-1 neutralizing antibodies. Seven seroconverters who became infected between 1982 and 1984 and 12 seroprevalents who were already seropositive in 1982 remained free of AIDS. During the 6 year period, 1 seroconverter and 14 seroprevalents developed AIDS. Healthy seroconverters developed neutralizing antibodies slowly and reached moderate geometric mean titers (GMT) of 1:100 within 3 years of seroconversion. Healthy seroprevalents already had moderate titers in 1982, which increased markedly in 1985-1986 (GMT greater than 1:200) and subsequently returned to the previous level in 1987. Neutralizing antibody titers declined 3 years prior to diagnosis in men who developed AIDS and reached levels significantly lower than those of healthy counterparts 2 years before diagnosis. Analysis of neutralizing antibody activity to several HIV-1 isolates indicated that the lower titers of men who developed AIDS were not due to diminished group-specific reactivity. Thus, high neutralizing antibody titers correlated with better clinical outcome, and low or decreasing neutralizing antibody titer signaled poor prognosis. Although naturally developing neutralizing antibodies may ultimately be inadequate in controlling disease progression, measures able to boost the neutralizing antibody titer of individuals already infected with the virus or to elicit high-titer neutralizing antibodies in individuals at risk may yet prove beneficial in controlling viral spread in vivo or in preventing new infection, presumably in concert with cellular immunity.

Acquired Immunodeficiency Syndrome↗

HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS.

HLA-A, -B, -C, -DR, and -DQ antigen phenotypes were determined in 266 Caucasian homosexual men, 90 of whom were HIV-1 seronegative, 94 HIV-1 seropositive AIDS-free, and 82 with a diagnosis of AIDS [36 with Kaposi's sarcoma (KS), 34 with opportunistic infection (OI), and 12 with KS and OI]. No significant differences in HLA-A or -B antigen frequencies were found in any comparisons of these groups. However, in comparisons of seropositive AIDS-free men with the AIDS groups, HLA-Cw7 was increased in frequency in OI and HLA-DR1, -DRw14, and -DQw1 in KS. HLA-DR3 and -DQw3 frequencies were decreased in KS, and DRw53 was decreased in OI. In a cohort of 102 HIV seropositive individuals that were followed for a mean of 43 months, AIDS developed in HLA-DR1 positive men more frequently than in individuals with other HLA-DR phenotypes (p = 0.02). These results demonstrate probable genetic differences between individuals developing KS and OI and indicate that the HLA-DR1 phenotype is a risk factor in disease progression in human immunodeficiency virus (HIV)-infected individuals.

Acquired Immunodeficiency Syndrome↗

AIDS update.

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Acquired Immunodeficiency Syndrome↗

What is safe sex? Suggested standards linked to testing for human immunodeficiency virus.

Because of the lethality of the HIV epidemic, rational and scientifically defined standards of sex that preclude the spread of sexually transmitted diseases are required. In the context of an HIV-antibody test that has been documented to be extremely sensitive and specific, standards for truly safe sex can be defined. HIV testing can be used as a powerful tool for defining a series of standards for sexual partners that eliminates, with reasonable certainty, the further spread of HIV. Such standards provide a defined benchmark for future research aimed at evaluating the effectiveness of public health measures in arresting the spread of the virus. The fact that at least 10 million American blood donors and some 2 million Americans applying for or in the armed forces have been tested demonstrates that the adverse consequences of testing can be limited. Now is the time to minimize the fear and eliminate the risk of transmitting HIV to loved ones by urging widespread voluntary testing of sexually active adults and by developing standards for safe sex.

Acquired Immunodeficiency Syndrome↗

Risk of AIDS after herpes zoster.

In a closed internal medicine practice for homosexual men in Central Manhattan herpes zoster developed in 112 men between 1980 and mid-1986. In these patients the incidence of acquired immunodeficiency syndrome (AIDS) was high: Kaplan-Meier survival analysis indicated cumulative incidences of AIDS of 22.8% within 2 years after herpes zoster, 45.5% within 4 years, and an estimated 72.8% after 6 years. Severity of zoster (relative risk, RR = 4.6), degree of pain (RR = 3.4), and zoster of the cranial or cervical dermatomes (RR = 2.2) were all associated with a poor outcome. Oral thrush, oral hairy leucoplakia, amoebiasis, and superficial (tinea) fungal infections also indicated an increased risk of AIDS among zoster patients. Oral thrush and oral hairy leucoplakia manifestations were diagnosed an average of 1.2 and 1.1 years, respectively, after the diagnosis of herpes zoster; thus zoster is an early indicator of an impaired immunity. Herpes zoster can be used as a predictor of AIDS and in AIDS risk groups should be regarded as a poor prognostic sign.

Acquired Immunodeficiency Syndrome↗

Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus.

We prospectively evaluated potential markers and cofactors for the acquired immunodeficiency syndrome (AIDS) in 86 homosexual men who were seropositive for human immunodeficiency virus antibodies. During three years of follow-up, 19 men developed AIDS. Risk of AIDS was clearly predicted by the total number of circulating OKT4-positive lymphocytes (T4 count) at enrollment, while the corresponding T8 count was unrelated to subsequent AIDS development. Subjects in Manhattan had a higher risk of Kaposi's sarcoma than did subjects in Washington, DC, and the risk of AIDS tended to increase with numerous homosexual partners. Several of 40 potential cofactors defined ex post facto, including receptive fellatio, enemas, methaqualone use, and high levels of antibody to hepatitis B surface antigen, appeared to be associated with Kaposi's sarcoma but not with Pneumocystis pneumonia. Our data suggest that potent cofactors for Pneumocystis pneumonia were not prominent, pointing to the need for effective drug therapies, particularly to reduce the high AIDS risk of persons with human immunodeficiency virus infection and low T4 counts.

Acquired Immunodeficiency Syndrome↗

Antiviral antibodies in the sera of homosexual men: correlation with their lifestyle and drug usage.

Healthy homosexual men between the ages of 21 and 65 years, from the Washington, DC (n = 162), and New York City (n = 89) areas, were studied for antibodies in the serum against cytomegalovirus (CMV), herpes simplex virus (HSV) types 1 and 2, and Epstein Barr virus (EBV) viral capsid antigen (VCA). CMV-specific antibodies were assayed by enzyme-linked immunosorbent assay (ELISA), anti-HSV-1 and -2 antibodies were measured by indirect hemagglutination (IHA), and antibodies to EBV VCA were measured by the immunofluorescence assay. Antibodies to human T lymphotrophic virus III (HTLV-III) were detected by ELISA and Western blot procedures. T lymphocytes were enumerated using OKT4 monoclonal antibody. Healthy male volunteer blood donors (n = 90) matched for age range and race proportions were used as controls. The percentage of seropositive individuals in the homosexual group was higher (90-98%) for all the viruses tested than in the control group (47-87%). Comparisons of the geometric mean titers, expressed as reciprocal serum dilutions, of seropositive individuals in homosexual (H) vs control (C) group were as follows: CMV-IgG (ELISA) H = 1:794, C = 1:68; HSV-1 (IHA) H = 1:248, C = 1:14; HSV-2 (IHA) H = 1:56, C = 1:17; EBV-VCA (IFA) H = 1:385, C = 1:131. The homosexual group also showed a higher frequency of individuals with elevated titers than the control group. The CMV IgM antibody was prevalent in 17.7% of the homosexual group and 5% of the control group; arithmetic means for ELISA values for CMV IgM were 0.207 for the homosexual group and 0.05 for the control group. In the homosexual group, the anti-CMV antibody titers increased with age (P = 0.01) and with numbers of sex partners (P = 0.06). Both anti-HSV-1 and anti-HSV-2 antibodies correlated with the number of sex partners (P = 0.04 and P = 0.05, respectively). Neither age nor partner number correlated with response to EBV, and no particular sex act was related to the EBV VCA titer level. HTLV-III seropositivity was associated with higher herpes virus group antibody titers, probably because of life style cofactors. Among the HTLV-III-seropositive subjects, those with less than or equal to 400 T-helper lymphocytes/mm3 had lower antibody titers than those with greater than 400 T-helper lymphocytes/mm3 counts, suggesting an impaired immune response secondary to immunosuppression.

Adult↗

Heterosexual transmission of human immunodeficiency virus: association with severe depletion of T-helper lymphocytes in men with hemophilia.

We evaluated risk factors for human immunodeficiency virus (HIV) seropositivity in the wives/female sexual partners of hemophiliacs. One of the 6 seropositive women has developed the acquired immunodeficiency syndrome (AIDS). At least three of the others seroconverted during 1985-86, after more than four years of regular sexual contact with a seropositive hemophiliac. HIV seropositivity was present in at least 5 (50%) of the 10 female partners of hemophiliacs with severe depletion of T-helper cells (less than 100/microliters), including 3 (43%) of the 7 female partners of hemophiliacs with AIDS. All 4 HIV seropositive women with available data had vaginal intercourse without a condom, but risk of seropositivity did not appear to be affected by the frequency of vaginal intercourse or by hysterectomy. Other sexually transmitted diseases, anal intercourse, or vaginal intercourse during menstrual periods were not necessary for HIV infection. These data suggest that heterosexual transmission of HIV can occur during routine vaginal intercourse but that it usually does not occur until the hemophiliac has severe immune deficiency late in the course of HIV infection.

Acquired Immunodeficiency Syndrome↗

Cancer in a group at risk of acquired immunodeficiency syndrome (AIDS) through 1984.

Using a proportional morbidity analysis method, the authors examined changes in the risk of malignancy among never-married men 20-49 years old (a surrogate population for homosexual men) in a high AIDS-risk area (City of San Francisco) and other lower AIDS-risk areas. This approach easily detected increases in Kaposi's sarcoma (odds ratio (OR) comparing 1973-1978 to 1984: 2,479-fold, proportional increase = 99.9%) and in non-Hodgkin's lymphomas (OR = 4.2-fold in 1984, p for trend less than 0.0001, proportional increase = 70%) in the City of San Francisco, with excesses especially in the Burkitt-like lymphomas and immunoblastic lymphomas. Extranodal lymphomas of the brain, but not other sites, were especially prominent (proportional increase = 96%). In addition, nonsignificant increases were seen for Hodgkin's disease (p for trend = 0.13) and for hepatoma (p for trend = 0.08). A posteriori, the authors noted increases in urinary tract tumors and acute lymphoblastic leukemia which warrant monitoring. Other tumors suggested to be AIDS-associated did not occur excessively in this population. Among single young men outside of San Francisco, Kaposi's sarcoma also increased significantly (OR = 182 in 1984), suggesting a lag of about three years behind the increases in the City of San Francisco. Some tumors may require a longer latent period before an association becomes manifest. In the meantime, however, these data indicate that the increases in AIDS-related cancers are limited to only a few malignancies.

Acquired Immunodeficiency Syndrome↗

Natural history of human immunodeficiency virus infections in hemophiliacs: effects of T-cell subsets, platelet counts, and age.

Serial T-cell subsets and platelet counts were determined in a cohort of 84 hemophiliacs in whom time of seroconversion for human immunodeficiency virus (HIV) antibody could be ascertained. An abrupt decrease in the number of T-helper (T4) cells was seen in 9 patients 12 to 24 months before the acquired immunodeficiency syndrome (AIDS) was diagnosed (p = 0.0007 compared with those who did not develop AIDS). Thrombocytopenia also was associated with an increased risk for AIDS (p = 0.02), as was older age at the time of seroconversion (p = 0.03). Ten patients developed AIDS at 24 to 95 months after seroconversion, for a cumulative incidence (+/- SE) of 18.0% +/- 7.1% at 6 years. Hemophiliacs who had T4 cell counts of less than 200 cells/microL had a 50% +/- 16% cumulative incidence of AIDS within 2 years, indicating that decreasing or very low T4 cell counts have predictive value for the development of AIDS. Furthermore, the data suggest that thrombocytopenia and older age may be markers for a cofactor that increases the risk for AIDS in hemophiliacs.

Acquired Immunodeficiency Syndrome↗

Three-year incidence of AIDS in five cohorts of HTLV-III-infected risk group members.

The incidence of the acquired immune deficiency syndrome (AIDS) among persons infected with human T-lymphotropic virus type III (HTLV-III) was evaluated prospectively among 725 persons who were at high risk of AIDS and had enrolled before October 1982 in cohort studies of homosexual men, parenteral drug users, and hemophiliacs. A total of 276 (38.1 percent) of the subjects were either HTLV-III seropositive at enrollment or developed HTLV-III antibodies subsequently. AIDS had developed in 28 (10.1 percent) of the seropositive subjects before August 1985. By actuarial survival calculations, the 3-year incidence of AIDS among all HTLV-III seropositive subjects was 34.2 percent in the cohort of homosexual men in Manhattan, New York, and 14.9 percent (range 8.0 to 17.2 percent) in the four other cohorts. Out of 117 subjects followed for a mean of 31 months after documented seroconversion, five (all hemophiliacs) developed AIDS 28 to 62 months after the estimated date of seroconversion, supporting the hypothesis that there is a long latency between acquisition of viral infection and the development of clinical AIDS. This long latency could account for the significantly higher AIDS incidence in the New York cohort compared with other cohorts if the virus entered the New York homosexual population before it entered the populations from which the other cohorts were drawn. However, risk of AIDS development in different populations may also depend on the presence of as yet unidentified cofactors.

Acquired Immunodeficiency Syndrome↗

Altered immunity in hemophilia correlates with the presence of antibody to human T-cell lymphotropic virus type III (HTLV-III).

Twenty-nine heterosexual patients with hemophilia were investigated with histories, physical examinations, laboratory evaluations of immune function, delayed hypersensitivity skin tests, and assays for antibody to human T-cell lymphotropic virus type III (HTLV-III). Sixteen patients were HTLV-III antibody positive and 13 were HTLV-III antibody negative. No patient had the acquired immune deficiency syndrome (AIDS). Patients who had antibody to HTLV-III had received significantly more units and lots of factor concentrates in the preceding 5 years than those who did not have antibody. HTLV-III antibody-positive patients had significantly fewer total T cells (Leu-1 positive) and significantly fewer helper T cells (Leu-3 positive) than HTLV-III negative patients. Antibody-positive patients also had increased amounts of IgG and decreased thymidine incorporation in response to concanavalin A in vitro. There were no differences in in vitro lymphocyte responses to phytohemagglutinin (PHA), pokeweed mitogen, Candida, tetanus, or purified protein derivative (PPD), no significant impairments of gamma interferon or interleukin-2 (IL-2) production, and no anergy. Ten patients with antibody to HTLV-III had immunologic studies repeated 1 year after the original evaluation. A significant increase was seen in suppressor (Leu-2-positive) T cells but not in total T-cell or helper T-cell numbers, helper/suppressor ratios, or T-cell functional assays. We conclude that the immune abnormalities in hemophiliacs are the result of contact with HTLV-III but that these abnormalities may remain stable over prolonged periods.

Adult↗

Antibodies to human T-lymphotropic virus type III and development of the acquired immunodeficiency syndrome in homosexual men presenting with immune thrombocytopenia.

In 35 homosexual men with isolated thrombocytopenia at initial presentation, who were evaluated and treated between 1982 and 1984, hematologic studies showed immune destruction. In contrast to findings in other autoimmune conditions, T-lymphocyte subsets in these patients were reversed, with a mean helper to suppressor ratio of 0.4 and with an absolute depletion of helper cells to 390/mm3. An enzyme-linked immunosorbent assay detected antibodies to human T-lymphotropic virus type III in 21 of 25 patients tested; Western blot analysis confirmed seropositivity in the other 4 patients, who had borderline findings. Although 19 of 24 patients treated with steroids responded, only 2 achieved sustained normal platelet counts. Ten of fifteen patients who had splenectomy achieved remissions. Three patients treated with steroids or splenectomy developed diagnoses compatible with the acquired immunodeficiency syndrome 16 to 34 months after their initial presentation with thrombocytopenia. These findings indicate that immune thrombocytopenia is part of the clinical spectrum of the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Long-term seropositivity for human T-lymphotropic virus type III in homosexual men without the acquired immunodeficiency syndrome: development of immunologic and clinical abnormalities. A longitudinal study.

The long-term effects of seropositivity for human T-lymphotropic virus type III (HTLV-III) on T-lymphocyte subsets and health status were evaluated in longitudinal studies of 250 initially healthy homosexual men. The relative risk of having an inverted T-lymphocyte helper-to-suppressor ratio rose from 14.3-fold among short-term seropositive subjects (less than 19 months) to 46.9-fold among long-term seropositive subjects (greater than 29 months) in comparison with the risk among seronegative subjects. Overall, 91.7% of long-term seropositive men had inverted ratios, compared with 12.9% of seronegative men. None of the seropositive men who developed an inverted ratio later reestablished a normal ratio. Both decreased T-helper cell number and percentage (p = 0.003) and increased T-suppressor cell number and percentage (p = 0.03) were significantly correlated with duration of seropositivity. Among seropositive persons, lymphadenopathy was a highly significant short-term as well as long-term consequence, whereas diarrhea, oral thrush, and herpes zoster were correlated with long-term seropositivity. Overall, 50% of long-term seropositive men compared with 16% of seronegative men developed at least one of five clinical symptoms (p less than 0.003). We conclude that a high proportion of persons infected with HTLV-III will develop measurable immunologic and clinical abnormalities.

Antibodies, Viral↗