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Biomedical subjects

S D Holmberg

Publications and source records attributed to S D Holmberg.

At least 19 recordsLinked to original sources

Increased incidence of Hodgkin disease in homosexual men with HIV infection.

OBJECTIVE: To evaluate the incidence of Hodgkin disease and non-Hodgkin lymphoma among homosexual men infected with human immunodeficiency virus (HIV). DESIGN: Cohort study with computer-matched identification of participants with the Northern California Cancer Center registry. Population rate comparisons were made with data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. PARTICIPANTS: The 6704 homosexual men in the San Francisco City Clinic Cohort study. MEASUREMENTS: Incidence of Hodgkin disease, non-Hodgkin lymphoma, HIV infection, and the acquired immunodeficiency syndrome (AIDS); calculation of sex and age-adjusted standardized morbidity ratios and attributable risk. RESULTS: Eight cases of Hodgkin disease and 90 cases of non-Hodgkin lymphoma were identified through computer matching among cohort members residing in the San Francisco Bay area from 1978 through 1989. Among the HIV-infected men, the age-adjusted standardized morbidity ratio was 5.0 (95% CI, 2.0 to 10.3) for Hodgkin disease and 37.7 (CI, 30.3 to 46.7) for non-Hodgkin lymphoma. The excess risk attributable to HIV infection was 19.3 cases of Hodgkin disease per 100,000 person-years and 224.9 cases of non-Hodgkin lymphoma per 100,000 person-years. CONCLUSION: An excess incidence of Hodgkin disease was found in HIV-infected homosexual men. Additional well-designed epidemiologic studies are needed to determine whether Hodgkin disease should be considered an HIV-related malignancy.

Adult

Testing for antibodies to human immunodeficiency virus type 2 in the United States.

The Food and Drug Administration (FDA) has recommended that all donated blood be screened for antibodies to human immunodeficiency virus type 2 (HIV-2) beginning no later than June 1, 1992. This article provides CDC recommendations for the diagnosis of HIV-1 and HIV-2 infections in persons being tested in settings other than blood centers and CDC/FDA guidelines for serologic testing with combination HIV-1/HIV-2 screening enzyme immunoassays (EIAs). Epidemiologic data indicate that the prevalence of HIV-2 infections in persons in the United States is extremely low. Therefore, CDC does not recommend routine testing for HIV-2 in settings other than blood centers. However, when HIV testing is indicated, tests for antibodies to both HIV-1 and HIV-2 should be obtained if epidemiologic risk factors for HIV-2 infection are present, if clinical evidence exists for HIV disease in the absence of a positive test for antibodies to HIV-1, or if HIV-1 Western blot results exhibit the unusual indeterminate pattern of gag plus pol bands in the absence of env bands. The following procedures are recommended if testing for both HIV-1 and HIV-2 is performed by means of a combination HIV-1/HIV-2 EIA. A repeatedly reactive specimen by HIV-1/HIV-2 EIA should be tested by HIV-1 Western blot (or another licensed HIV-1 supplemental test). A positive result by HIV-1 Western blot confirms the presence of antibodies to HIV, and testing for HIV-2 is recommended only if HIV-2 risk factors are present. If the HIV-1 Western blot result is negative or indeterminate, an HIV-2 EIA should be performed. If the HIV-2 EIA is positive, an HIV-2 supplemental test should be performed.

AIDS Serodiagnosis

Serum beta 2-microglobulin and prediction of progression to AIDS in HIV infection.

Identification of laboratory tests that can help predict progression to acquired immunodeficiency syndrome (AIDS) in people infected with human immunodeficiency virus (HIV) is important for clinical management and counselling. We have assessed the usefulness of CD4 lymphocyte count, serum beta 2-microglobulin concentration, and the presence of p24 antigen as predictors of AIDS. We studied 214 homosexual and bisexual men with well-defined dates of HIV seroconversion. For each participant, we defined the baseline date as the earliest date before the development of AIDS on which the three laboratory tests were done. beta 2-microglobulin concentration at baseline was in all analyses an independent predictor of AIDS, even after stratification by baseline CD4 count, duration of HIV infection, or use of zidovudine before or at baseline. For example, among men with at least 0.5 x 10(9)/l CD4 cells who were negative for p24 antigen, the risks of AIDS at 12 months and 24 months were 1% and 5%, respectively, for those whose beta 2-microglobulin concentrations were below 4.0 mg/l, compared with 17% and 27%, respectively for those with beta 2-microglobulin concentrations above that cut-off point (p less than 0.001). Among men with an estimated duration of infection of 5 years or less, beta 2-microglobulin concentration was the strongest independent predictor of AIDS. Measurement of serum beta 2-microglobulin adds important prognostic information to CD4 count in determining the risk of progression to AIDS in HIV-infected subjects, including those whose CD4 cell count has not yet fallen.

Acquired Immunodeficiency Syndrome

Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor.

BACKGROUND: Since 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. METHODS: We 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. RESULTS: HIV-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. CONCLUSIONS: Although 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.

Acquired Immunodeficiency Syndrome

The relation between nitrite inhalants, unprotected receptive anal intercourse, and the risk of human immunodeficiency virus infection.

The role of nitrite was evaluated between 1985 and 1988 in a study of sexual transmission of the human immunodeficiency virus (HIV) among homosexual male couples in Boston, Massachusetts. Initial enrollment data suggested that a history of unprotected receptive anal intercourse (odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.4-3.6) and a history of nitrite use (OR = 1.7, 95% CI 1.1-2.5) were independent risk factors for HIV infection. In addition, interaction between nitrite use and unprotected receptive anal intercourse was observed (OR = 5.5, 95% CI 2.8-11.1) after controlling for number of unprotected receptive anal sex partners and history of sexually transmitted diseases. Since it was felt that nitrite use might be a marker for unprotected receptive anal sexual activity, a supplemental questionnaire was administered to obtain information on simultaneous nitrite use and unprotected receptive anal intercourse. The supplemental data suggested a strong interaction between nitrite use and unprotected receptive anal intercourse in increasing the risk of HIV infection. In the adjusted analyses, the odds ratio for HIV infection was considerably greater among men who always used nitrites during unprotected receptive anal intercourse (OR = 31.8, 95% CI 12.9-76.7) compared with men who sometimes (OR = 7.1, 95% CI 2.1-23.6) or never (OR = 9.0, 95% CI 2.5-32.1) used them. These findings have preventive public health implications and may add insight into our understanding of the mechanism by which HIV infection spread rapidly among homosexual men in the early 1980s.

Adult

Herpes zoster and human immunodeficiency virus infection.

The interaction of herpes zoster and the human immunodeficiency virus (HIV) was evaluated in a cohort study of 287 homosexual men with well-defined dates of HIV seroconversion and 499 HIV-seronegative homosexual men. The incidence of herpes zoster was significantly higher among HIV-seropositive men (29.4 cases/1000 person-years) than among HIV-seronegative men (2.0 cases/1000 person-years); the overall age-adjusted relative risk (RR) was 16.9 (95% confidence interval [CI], 8.7-32.6). When compared with that of age-matched population controls from 1945 to 1959, the incidence of zoster was significantly higher among seropositive men (RR, 26.7; 95% CI, 19.3-37.1) and slightly higher among seronegative men (RR, 1.85; 95% CI, 1.0-3.3); the latter may reflect increasing background rates over several decades. The risk of herpes zoster was not associated with duration of HIV infection and was not predictive of faster progression to AIDS.

Adult

Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics.

From a prospective cohort study, 24 asymptomatic men were identified who had been antibody positive for human immunodeficiency virus (HIV) for at least 5 years (median = 9.1) with CD4+ lymphocyte counts greater than or equal to 400 cells/mm3. Of these "nonprogressors", 23 (96%) had evidence of HIV infection by either HIV culture or the polymerase chain reaction (PCR) for HIV DNA, although only 1 (4%) had a positive assay for HIV RNA (by PCR) and no one was positive for p24 antigen. Compared with 24 antibody-negative men and 14 men with AIDS, nonprogressors had higher CD8+ counts and lower natural killer cell activity. Nonprogressors had higher beta 2-microglobulin levels than did seronegative controls, suggesting some degree of immune system activation. Compared with men with AIDS, nonprogressors seemed to have a stronger antibody response to six different HIV-related proteins but did not differ significantly in neutralizing antibody or antibody-dependent cellular cytotoxic activity.

Adult

HIV-2 infection in an American.

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.

Adult

The association of clinical conditions and serologic tests with CD4+ lymphocyte counts in HIV-infected subjects without AIDS.

Early intervention guidelines in HIV infection require knowledge of CD4+ lymphocyte count; however, CD4+ determinations require special laboratory procedures and may not be readily available in all situations. Using data from 207 HIV-seropositive homosexual men without AIDS, we evaluated the association of difference clinical conditions or serologic tests with CD4+ count. Men with conditions including seborrheic dermatitis, hairy leukoplakia, oral candidiasis and chronic diarrhea, and men with beta2-microglobulin levels greater than or equal to 4.0 mg/l had significantly lower CD4+ counts. However, the probability that a subject with such parameters had less than 200 x 10(6)/l CD4+ cells was limited (25-63%). Although the probability that a subject with such parameters had less than 500 x 10(6)/l CD4+ cells was better (76-88%), the probability that a person without these parameters had greater than or equal to 500 x 10(6)/l CD4+ cells was only 45-50%. Clinical and serologic parameters may provide important prognostic information, but cannot be used to reliably determine the level of CD4+ cells.

Bisexuality

Concordance of polymerase chain reaction with human immunodeficiency virus antibody detection.

To evaluate the correlation of detection of human immunodeficiency virus (HIV) by polymerase chain reaction (PCR) with detection of HIV antibody, 271 simultaneous serum and peripheral blood mononuclear cell samples were examined from 242 persons whose activities placed them at increased risk for HIV infection: 142 from homosexual men, 86 from hemophilic men, and 43 from heterosexual partners of HIV-infected persons. PCR was performed using the gag region primer pair SK38/39 and the env region primer pairs SK68/69 and CO71/72. Amplified HIV DNA was detected using specific oligomer probes. Of 63 HIV antibody-positive samples, 58 (92%) had HIV DNA by PCR. Of 208 HIV antibody-negative samples, 7 (3.4%) had HIV DNA by PCR. On follow-up, 4 of the latter persons were seropositive when next tested; 2 were well and antibody- and PCR-negative; 1 had died of a stroke before retesting. Thus, PCR detects HIV in most antibody-positive persons; detection is increased by use of multiple primer pairs. PCR-positive antibody-negative specimens may indicate HIV infection in which antibody has not yet developed or may be false-positive PCR results. When PCR is discordant with HIV antibody, testing of additional specimens and clinical follow-up are necessary to assess HIV infection status.

Bisexuality

The rise of tuberculosis in America before 1820.

Bills of mortality, newspaper and gazette articles, journals, and other records with specific references to "consumption," "phthisis," and other terms for tuberculosis were reviewed to determine the occurrence and importance of tuberculosis in the American colonies before 1820. Review of these sources indicates a marked increase in the proportional mortality from tuberculosis in the United States in the 18th century. "Consumption" may have been the leading cause of death in adult American colonists.

History, 18th Century

Possible cofactors for the development of AIDS-related neoplasms.

Because of the various neoplastic manifestations of human immunodeficiency virus (HIV) and the variable period between HIV infection and the development of tumors related to acquired immunodeficiency syndrome (AIDS), it is possible that certain behaviors, toxins, genes, or infectious agents--particularly viruses--may act as cofactors in the pathogenesis of AIDS-related neoplasms. Most epidemiologic and laboratory investigations of possible cofactors have been directed toward Kaposi's sarcoma (KS), by far the most common AIDS-related tumor and one closely associated with male homosexual lifestyle in the U.S. Nonetheless, epidemiologic investigations of putative associations have not demonstrated any clear association between KS and particular viruses. Furthermore, laboratory investigations, both serologic and molecular/genetic, have failed to definitively implicate as cofactors for KS these viruses: cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses, pathogenic human papillomaviruses, or human herpes virus type 6. Investigations of a suggested association between EBV and AIDS-associated non-Hodgkin's (B cell) lymphomas (NHLs) have also been inconclusive. However, HIV may act as a cofactor in accelerating the development of hepatitis B-associated hepatocellular carcinoma. In summary, viral or other cofactors have not been definitely identified as cofactors in AIDS-related tumors.

Acquired Immunodeficiency Syndrome

Duration of human immunodeficiency virus infection before detection of antibody.

To estimate the duration and frequency of the period of HIV infection without detectable antibody, modelling techniques were applied to results of detection of HIV DNA by means of the polymerase chain reaction (PCR) and to data from cases in published reports. PCR was carried out with gag and env region primers on samples from 27 homosexual and 12 haemophilic men for whom stored samples were available from before and after seroconversion; serum was also tested for p24 antigen by antigen-capture enzyme immunoassay. HIV DNA was detectable before seroconversion in 4 men; in all 4 PCR was positive only in the seronegative sample taken closest to the time of seroconversion. In 3 men antigen was detected before seroconversion; in each case HIV DNA was also detected. By a Markov model, the time from infection with HIV (as assessed by detection of HIV DNA) to first detection of HIV antibody was estimated to be 2.4 (SE 2.1) months for the median individual. Modelling of cases of HIV infection with known exposure in published reports gave a median estimate of 2.1 (0.1) months from exposure to antibody detection, and 95% of cases would be expected to seroconvert within 5.8 (0.6) months. HIV infection for longer than 6 months without detectable antibody seems uncommon.

Acquired Immunodeficiency Syndrome