Danish Homosexual Men Research Articles

Risk factors for Kaposi's-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996.

A newly identified herpesvirus has been associated with Kaposi's sarcoma. We determined risk factors for Kaposi's-sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) seropositivity and incidence of infection over time in a cohort of Danish homosexual men followed from 1981 to 1996. Antibodies to a latent nuclear (LANA) and a structural (orf65) antigen of KSHV/HHV-8 were measured by immunofluorescence and ELISA/WB respectively. Through linkage with the national AIDS registry, all cohort members diagnosed with AIDS as of September 1996 were identified and their hospital records were scrutinized to record all diagnoses of KS. Overall, 21.1% (52/246) of the men were KSHV/HHV-8-seropositive in 1981. Among the initially seronegative, the rate of KSHV/HHV-8 seroconversion was highest between 1981 and 1982 and declined steadily thereafter. In a multivariate analysis of the status at enrollment in 1981, KSHV/HHV-8 seropositivity was not associated with age but was independently associated both with number of receptive anal intercourses (OR = 2.83; p = 0.03) and with sex with US men (OR = 2.27; p < 0.05). In a multivariate analysis of follow-up data, risk of KSHV/HHV-8 seroconversion was independently associated with having visited homosexual communities in the United States, and current HIV-positive status. More than 5 years' homosexual experience was associated with an insignificantly increased risk (RR = 2.68). KS occurred only in HIV-positive men who were KSHV/HHV-8-positive at or prior to their KS diagnosis. In conclusion, KSHV/HHV-8 appears to be sexually transmitted, probably by receptive anal intercourse, and may have been introduced to Danish homosexual men via sex with US men. The epidemic of KSHV/HHV-8 is now declining. These findings are concordant with the view that KSHV/HHV-8 may have been actively spread simultaneously with and by the same activities that lead to the spread of HIV.

Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals.

Recently, it has been shown that a homozygous 32 base-pair deletion in the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1. We have investigated whether HIV-seropositive individuals who were heterozygous for the CKR-5 deletion had a different course of the disease. Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive Danish homosexual men followed form 1985 to 1996 and 37 blood donors were analysed for their CKR-5 genotype by polymerase chain reaction. Two (6%) of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV-seropositive subjects were heterozygous and none was homozygous. Two subgroups of patients who had an opposite course of the HIV disease were identified. Of nine long-term non-progressors, six (66%) were heterozygous for the deletion. This frequency is significantly higher than in nine rapid progressors of whom non was heterozygous. The frequency of heterozygotes in long-term non-progressors was also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly better prognosis within the first 7 years of follow-up for those who were heterozygous for the deletion. Heterozygous individuals also had a significantly slower decrease in CD4 T-cell count per year. Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

Regression models for interval censored survival data: application to HIV infection in Danish homosexual men.

This paper shows how to fit excess and relative risk regression models to interval censored survival data, and how to implement the models in standard statistical software. The methods developed are used for the analysis of HIV infection rates in a cohort of Danish homosexual men.

USE OF A LOG‐LINEAR MODEL TO COMPUTE THE EMPIRICAL SURVIVAL CURVE FROM INTERVAL‐CENSORED DATA, WITH APPLICATION TO DATA ON TESTS FOR HIV POSITIVITY

SummaryWe describe how a log‐linear model can be used to compute the nonparametric maximum likelihood estimate of the survival curve from interval‐censored data. This permits such computation to be performed with the aid of readily available statistical software such as GLIM or SAS. The method is illustrated with reference to data from a cohort of Danish homosexual men, each of whom was tested for HIV positivity on one or more of six possible follow‐up times.

A preliminary report on the neuropsychologic sequelae of human immunodeficiency virus.

The neuropsychologic sequelae of acquired immunodeficiency syndrome and human immunodeficiency virus were studied by comparing the results of a neuropsychologic test battery administered to the following three groups of Danish homosexual men: 20 patients with acquired immunodeficiency syndrome, 20 asymptomatic subjects who tested positive for the human immunodeficiency virus, and a matched control group of 20 subjects who tested negative for the human immunodeficiency virus. The group with acquired immunodeficiency syndrome performed significantly worse than the control subjects on the tests measuring concentration, memory, and psychomotor speed. The group with human immunodeficiency virus performed significantly worse than the control subjects on the tests measuring verbal memory and psychomotor speed. On the other tests, their results varied. The study supports the hypothesis that not only patients with acquired immunodeficiency syndrome but also asymptomatic subjects with human immunodeficiency virus may be neuropsychologically impaired early in the course of the disease.

Immune status as a determinant of human papillomavirus detection and its association with anal epithelial abnormalities

One hundred and twenty Danish homosexual men were enrolled to characterize risk factors for anal type-specific human papillomavirus (HPV) expression and to examine its association with anal epithelial atypia. Detection of HPV strongly correlated with immunosuppression measured by T-lymphocyte subset markers and rose nearly linearly from 7.3% among subjects with CD4/CD8 ratios above 1.0 to 35.3% among those with a ratio below 0.4 (p trend = 0.003). No association was found between presence of HPV and a wide range of lifestyle factors including number of sex partners/year, smoking, alcohol consumption and illegal drug intake. However, self-reported history of anal condyloma in the past year was correlated with HPV (p less than 0.001). Simultaneous testing for presence of HPV in the oral cavity showed evidence of HPV 16,18 and 31,33,35. Anal smears were abnormal in 19.5% of the men and correlated strongly with presence of HPV (OR = 6.1, p less than 0.001). Type-specific associations were found with HPV 31/33/35 (OR = 8.5) and HPV 16/18 (OR = 3.1) only. The association remained significant after adjusting for immune status. Overall, HPV was detected in 50% of the cases with abnormal smears. However, HPV was found in all subjects with abnormal smears and a CD4/CD8 ratio below 0.4, compared to only 3 of 14 subjects with abnormal smears and a ratio greater than or equal to 1.3. In conclusion, (1) HPV may be missed in a substantial number of infected subjects with a normal immune system. This may have an impact on studies trying to describe risk factors for HPV transmission and its correlation with cancer development. (2) The finding of HPV 16,18 and 31,33,35 in the oral cavity makes oral-genital sexual activity at least a hypothetical route of transmission for these HPV types. (3) HPV appears to play a central role in the development of anal epithelial abnormality.

Sequential HTLV-III antibody studies in Danish homosexual men.

Sequential HTLV-III antibody studies in Danish homosexual men.

White piedra andTrichosporon beigeliicarriage in homosexual men

Trichosporon beigelii was isolated from the anal region in 45 (13%) of 343 Danish homosexual men. T. beigelii was also present on the scrotal skin of six anal carriers who were accessible for re-examination, and white piedra of the genital hair was observed in two cases. Because T. beigelii may cause systemic infections in compromised hosts it may pose a threat to homosexuals infected by HTLVIII/LAV virus.

Variation in human T lymphotropic virus III (HTLV-III) antibodies in homosexual men: decline before onset of illness related to acquired immune deficiency syndrome (AIDS).

Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.

Low T-Lymphocyte Ratios in Homosexual Men

To investigate risk factors for immunologic abnormalities among homosexual men, T-lymphocyte helper/suppressor (OKT4/OKT8) ratios were determined in 78 healthy Danish homosexual men. Ratios in 26 men (33%) were low (less than 1.00). Visiting the United States in 1980 to 1981 was a strong (7.7-fold) risk factor for having a ratio less than 1.00. Among nine travelers who visited only once, the risk of having a low ratio increased significantly if the visit had occurred in 1981. A risk of similar magnitude (6.9-fold) was found among the three men who had not been to the United States but who reported homosexual contact with a Danish man who became ill with Kaposi's sarcoma. Risk of low ratios did not correlate with age or years of homosexual activity. Promiscuity was not a significant risk factor, but these men generally had fewer sex partners than that which has been reported from the United States. Neither nitrite inhalant use nor cytomegalovirus antibody (prevalence or titer) was associated with low ratios. These data support the hypothesis that a transmissible biologic agent may be etiologically responsible for the low helper/suppressor ratios in homosexual men.

Seminal fluid excretion of cytomegalovirus related to immunosuppression in homosexual men.

Seminal fluid samples from 84 Danish homosexual men were successfully cultured to determine the prevalence of cytomegalovirus excretion. Ten (15%) out of 66 men positive for the antibody were found to be excreting the virus. Although the proportion excreting was inversely related to age (p less than 0.01), three men aged over 30 and with many years of homosexual experience excreted the virus. In addition, a 50 year old man with Kaposi's sarcoma excreted the virus. A further study of the ratio of T cell helpers to suppressors in the men aged over 30 and a series of age matched non-excreting homosexual control or heterosexual men showed that those excreting cytomegalovirus in their seminal fluid had statistically lower ratios (all less than 0.77) than the controls (p less than 0.05). Excretion of cytomegalovirus may be related to re-emergence of latent infection in immunosuppressed homosexual men.

Immunologic studies in healthy Danish homosexual men.

Immunologic studies in healthy Danish homosexual men.