Elevated seroprevalence of human herpesvirus 8 among men with prostate cancer

Background. To investigate any epidemiological association between human herpesvirus (HHV)-8 and prostate cancer, we determined the prevalence of HHV-8 seropositivity among prostate cancer case and control subjects in the United States and Trinidad and Tobago.Methods. Antibodies against HHV-8 were detected in 2 independent laboratories using either indirect immunofluorescence assay (IFA) or a combination of enzyme-linked immunosorbent assay and IFA.Results. Among 138 Tobago men with prostate cancer, HHV-8 seroprevalence was 39.9%-significantly higher than that among 140 age-matched control subjects (22.9%; P=.003; odds ratio [OR], 2.24; 95% confidence interval [CI], 1.29-3.90). Among 100 US men with prostate cancer, seroprevalence was 20%-significantly higher than that of 177 blood donors (5.1%; P=.001; OR, 4.67; 95% CI, 1.91-11.65) and higher than that of 99 men with cancer not related to HHV-8 (13%; P=.253; 95% CI, 0.77-3.54).Conclusions. HHV-8 seropositivity is elevated among men with prostate cancer compared with control subjects, which suggests that HHV-8 plays a role in the development of prostate cancer.     

Frequent and asymptomatic oropharyngeal shedding of human herpesvirus 8 among immunocompetent men

BACKGROUND: Little is known about the clinical and virologic manifestations of human herpesvirus (HHV)-8 infection in immunocompetent persons in the absence of malignancy. METHODS: A total of 46 human immunodeficiency virus-negative, HHV-8-seropositive men collected saliva daily, and 25 recorded 15 common symptoms daily (gastrointestinal, constitutional, and oropharyngeal) and absences from work or school. Quantitative polymerase chain reaction measured HHV-8 DNA in saliva. RESULTS: Some 44 (96%) of 46 men reported having sex with men (MSM). Of the 44 MSM, 27 (61%) had HHV-8 detected in saliva on > or = 1 day; heterosexual men also shed HHV-8. In analyses restricted to MSM, HHV-8 DNA was detected on 636 (22%) of 2897 days. Among MSM with HHV-8 detected in saliva, the median rate was 20% (range, 1%-100%), with 30% shedding on > 50% of days, and the median quantity was 4.5 log10 copies/mL (range, 2.0-7.3 log10 copies/mL). The quantity of HHV-8 shed was lower in nonwhites (P<.001) and younger participants (P=.03). The frequency of HHV-8 detection and quantity were correlated (r=0.62; P<.001). Symptoms were reported on 10 (9%) of 114 days when HHV-8 was present, compared with 78 (9%) of 830 days without (odds ratio, 0.93 [95% confidence interval, 0.30-2.88]; P=.9). CONCLUSIONS: HHV-8 is detected frequently and intermittently in the saliva of chronically infected immunocompetent MSM, but this infection is asymptomatic.     

Demographic and immune correlates of human herpesvirus 8 seropositivity in Malawi, Africa.

BACKGROUND: In the USA, human herpesvirus 8 (HHV-8) is associated with Kaposi's sarcoma (KS) and HIV infection. We examined HHV-8 seroprevalence in a Malawian cohort, and assessed its relationship with HIV, KS, demographic characteristics, and immune findings. METHODS: In 1997 and 1998, blood samples were obtained from 272 hospitalized Malawian patients, for whom demographic information was obtained, and 24 healthy volunteers without demographic data. We used enzyme immunoassays to assess seroprevalence and antibody titers to peptide antigens derived from HHV-8 K8.1 and ORF65-encoded proteins. Intracellular cytokines and cell surface antigens were assessed with four-color flow cytometry. Data were analyzed using non-parametric univariate and regression analytic techniques. RESULTS: The rates of HHV-8 seroprevalence to either or both HHV-8 peptides were 67% for the patients and 54% for the healthy volunteers. Seroprevalence increased with patients' age (P<0.001) but was not associated with HIV status, percentage of lymphocytes expressing CD4, or KS (n=10). Seropositive females had lower antibody titers to both peptides than did males (medians: 455 versus 1361 for K8.1, P<0.001; and 268 versus 405 for ORF65, P=0.044). For the healthy volunteers, the percentage of CD8+ cells producing IFN-gamma after stimulation was significantly lower in ORF65-specific antibody-positive persons (medians: 24% versus 57%, P=0.008). CONCLUSIONS: In Malawi, HHV-8 is endemic and is not associated with HIV infection or HIV severity. Seroprevalence rates increase in childhood, and, most steeply in adolescence. Titers are higher in seropositive males than in sero-positive females. The immune effects of HHV-8 in healthy adults are consistent with chronic inhibition of type 1 cytotoxic T-cell responsiveness, independent of HIV status.     

Serologic evidence of human herpesvirus 8 transmission by homosexual but not heterosexual sex.

Epidemiologic studies link Kaposi's sarcoma with a sexually transmitted agent. Human herpesvirus 8 (HHV-8) is likely to be that agent, but routes of transmission are poorly described. A seroepidemiologic study was conducted to determine whether HHV-8 is transmitted sexually between heterosexuals. Sera from 2718 patients attending a sexually transmitted disease (STD) clinic were tested for antibodies to HHV-8 and herpes simplex virus type 2 (HSV-2). Information on sex partners in the previous 12 months and past STDs were obtained by questionnaire. Relationships between possible risk factors and HHV-8 infection were assessed by logistic regression. Overall, seroprevalence of HHV-8 was 7.3%. Independent risk factors for HHV-8 in the whole group were homo/bisexuality and birth in Africa and, among homo/bisexual men, a history of syphilis and HSV-2 and human immunodeficiency virus seropositivity. Among heterosexuals there was no evidence for sexual transmission; the only independent risk factor for HHV-8 seropositivity was birth in Africa.     

Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort study of trucking company workers in Kenya

OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees. METHODS: HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior. RESULTS: The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/driver's assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute. This population is an appropriate target for HIV-1 prevention trials and behavioral interventions.     

Seroprevalence of human herpesvirus 8 among injection drug users in San Francisco

The association between injection drug use and human herpesvirus 8 (HHV-8) was examined to investigate bloodborne transmission of the virus. In all, 1905 injection drug users (IDUs) enrolled in a cross-sectional study were tested for K8.1 antibodies to HHV-8 lytic antigen. Logistic regression was used to adjust for demographic and sexual behavior variables. HHV-8 seroprevalence was 10% among women, 10% among heterosexual men, and 23% among men who have sex with men. In adjusted analyses, HHV-8 seroprevalence increased with longer duration of injection drug use for each of these groups (P = .01, P = .03, and P = .049 for trend, respectively). HHV-8 infection is relatively common among IDUs in San Francisco, and longer duration of injection drug use is associated with an increase in the risk of HHV-8 infection that is not explained by sexual behavior or demographic differences. These results are consistent with the occurrence of bloodborne transmission of HHV-8 among IDUs.     

Correlates of prevalent and incident Kaposi's sarcoma-associated herpesvirus infection in men who have sex with men

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is common among men who have sex with men (MSM). To determine correlates of infection, 578 human immunodeficiency virus (HIV)-negative MSM were assessed by serologic assays, questionnaires, and physical examinations. At baseline, 76 (16%) of 474 participants were KSHV seropositive. Prevalent KSHV infection was significantly associated with hepatitis A (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.5-7.5), hepatitis B seropositivity (OR, 2.6; 95% CI, 1.4-4.8), herpes simplex virus (HSV)-2 (OR, 2.4; 95% CI, 1.3-4.4), and >4 male partners in the previous 6 months (OR, 1.9; 95% CI, 1.1-3.2). Fifteen KSHV seroconversions (4%) were observed for an incidence of 3.8/100 person-years, similar to HSV-1 incidence in this cohort and more frequent than incidence of HIV and HSV-2. Reporting > or =1 HIV-positive partner (OR, 5.9; 95% CI, 1.8-19.3), amyl nitrite use (OR, 7.0; 95% CI, 2.1-23.0), and lymphadenopathy in the past 6 months (OR, 7.7; 95% CI, 1.9-31.0) correlated with KSHV seroconversion.     

Risk factors for Kaposi's sarcoma in men seropositive for both human herpesvirus 8 and human immunodeficiency virus

OBJECTIVE: To identify risk factors for Kaposi's sarcoma (KS) among men seropositive for both human herpesvirus 8 (HHV-8) and HIV. DESIGN: Cross-sectional study of 91 HHV-8 seropositive, HIV seropositive men who have sex with men (57 with KS), and 70 controls at lower risk for KS. METHODS: Patients received clinical evaluations. Blood, oral fluids, semen, rectal brush, rectal swab, and urine were collected, and tests for HHV-8 were performed. RESULTS: Men with KS were more likely to have HHV-8 DNA in peripheral blood mononuclear cells (PBMC) than men without KS [35.1 versus 5.9%, odds ratio (OR), 8.6, 95% confidence interval (CI), 1.9-39.9]. The prevalence of HHV-8 DNA in oral fluids was similar for the two groups (37.0 versus 32.4%; OR, 1.2; 95% CI, 0.5-3.0). HHV-8 DNA was rarely detected in specimens of other types from these men, or in any specimens from the 70 controls. Among men with KS, HHV-8 DNA in PBMC was associated with new KS lesions (OR, 4.5; 95% CI, 1.4-14.5), and HHV-8 DNA in oral fluids was associated with oropharyngeal KS lesions (OR, 3.1; 95% CI, 1.0-10.1). Men with high HHV-8 antibody titers were more likely to have KS (OR, 9.6; 95% CI, 1.2-78.2), but were less likely to have new KS lesions (OR, 0.2; 95% CI, 0.0-1.1) or HHV-8 DNA in PBMC (OR, 0.2; 95% CI, 0.0-1.6) or oral fluids (OR, undefined; = 0.001). CONCLUSIONS: In HHV-8- and HIV-seropositive men, HHV-8 DNA is associated with KS. Among men without KS, HHV-8 DNA is most commonly found in oral fluids. High HHV-8 antibody titers may protect against circulating HHV-8 and new KS lesions.     

Human herpesvirus 8 cellular immune responses in homosexual men.

Little is known about cellular immunity to human herpesvirus 8 (HHV-8), the virus associated with Kaposi's sarcoma (KS). T cell proliferative responses to purified HHV-8 were measured in homosexual men, a group with elevated HHV-8 seroprevalence and high risk of KS. None of 20 blood donor controls had T cell responses to HHV-8. Among human immunodeficiency virus (HIV)-negative homosexual men, 8 (42%) of 19 HHV-8 seropositive men responded as did 4 (16%) of 25 HHV-8 seronegative men. Among HIV-positive homosexual men, however, none of 21 HHV-8 seropositives had T cell responses to HHV-8, even though most responded to common recall antigens, and 10 had >/=400 CD4 cells/mm3. The results suggest that HHV-8 T cell proliferative responses are common in HIV-negative homosexual men and that HIV infection may be associated with diminished HHV-8 cellular immunity, possibly before there is substantial depletion of CD4 cells. If correct, this could explain why KS occurs relatively early in HIV infection/AIDS.     

男男性接触者异性性行为特征的调查研究

目的了解男男性接触者异性性行为的特征及其影响因素。方法于2005年7～11月，在北京市招募男男性接触者进行问卷调查，内容包括社会人口学和高危性行为特征。结果在526名男男性接触者中，10．6％（56／526）的人在近6个月与女性发生过性关系，其中有8．2％（43／526）和4．4％（23／526）的人分别与配偶／固定女性性伴和临时女性性伴发生过性行为，其与配偶／固定女性性伴和临时女性性伴发生阴道性交时，100％使用安全套的比例分别为32．6％（14／43）和34，8％（8／23）。多因素Logistic回归分析结果显示，结婚／与女朋友同居（OR=9．6，95％C13．8～24．4）、首次性交对象为女性（0R=9．7，95％C14，7～20．0），近6个月有固定男性性伴（0R=0，4，95％C10．2～0．8）、近6个月向同性卖淫（0R=5．0；95％C12．0～12．3）、近6个月每月饮酒（OR=3．8；95％C11，8～8，2）与男男性接触者近6个月发生异性性行为的关系有统计学意义。结论男男性接触者是HIV传播的桥梁人群，需要加大对该人群的干预力度，以控制HIV通过该人群向女性人群扩散。     

Transmission of human herpesvirus 8 by sexual activity among adults in Lagos,Nigeria

BACKGROUND: Human herpesvirus 8 (HHV-8) infection is common in Africa, but prevalence varies geographically. Studies in Europe and America suggest spread through homosexual contact, but evidence of heterosexual spread is inconsistent. We examined the association between HHV-8 and markers of risky sexual activity in Nigeria. METHODS: The study subjects included an adult referent population at relatively low risk of HIV infection, patients attending a sexually transmitted disease (STD) clinic, and female commercial sex workers (CSW). Sera were collected between 1991 and 1994 to study the epidemiology of retroviruses and STD in Lagos, Nigeria. Residual samples were tested for HHV-8 antibodies using a K8.1 enzyme immunoassay and for antibodies to syphilis, chancroid, herpes simplex virus 2, HIV-1/2, and HTLV-1. Associations were sought using chi square tests and logistic regression. RESULTS: Overall, HHV-8 prevalence was 26.5% in 2002 study subjects, being higher among CSW and STD patients (31% in each) than in the referent population (19%). HHV-8 prevalence in women was approximately half that in men in both the referent and the STD populations. Increasing age and STD were each associated with HHV-8-seropositivity in men and women, and among women being a CSW was also a risk factor. HHV-8 antibodies were more frequently detected in those with laboratory evidence of STD in each group. Having at least one STD was associated with having HHV-8 antibodies. CONCLUSION: The higher prevalence of HHV-8 antibody in groups with multiple sexual partners and the association with STD among individuals both support the sexual transmission of HHV-8 in African adults.     

Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa,Kenya

Human herpesvirus 8 (HHV-8) infection is very prevalent in sub-Saharan Africa, but the role of sexual transmission has not been well characterized. HHV-8 seroprevalence and correlates were evaluated in a cohort of female prostitutes in Mombasa, Kenya. Between February 1993 and January 2000, stored plasma samples taken from 736 women were tested, by whole-virus ELISA assay, for the presence of HHV-8 antibodies; of these 736 women, 633 were included in the analysis of correlates of HHV-8 infection; and, of these 633, 44.1% were seropositive for HHV-8 antibodies. In univariate analysis, age, years of education, years of prostitution, workplace, hormonal contraception, intrauterine-device use, alcohol consumption, syphilis, and gonorrhea were all significantly associated with the presence of HHV-8 antibodies. In a multivariate model, older age, fewer years of education, and 2 markers of high-risk sexual behavior-namely, alcohol consumption and gonorrhea-were each independently associated with HHV-8 seropositivity. These results suggest that heterosexual transmission may contribute to acquisition of HHV-8 infections in this African population of prostitutes.     

Reactivation of and primary infection with human herpesvirus 8 among solid-organ transplant recipients

Human herpesvirus 8 (HHV-8) is the causal agent of all forms of Kaposi's sarcoma, including the iatrogenic form that presents in solid-organ transplant recipients. A longitudinal study of HHV-8 seropositivity was conducted among a cohort consisting of children and adult solid-organ transplant recipients. Antibodies to HHV-8 lytic proteins were detected by an indirect immunofluorescence assay in serum samples of 100 transplant recipients. HHV-8 seropositivity increased significantly, from 5.3% before transplantation to 15.8% after transplantation (P<.01). Seropositivity was not related to the age of the patient or the type of organ transplanted. HHV-8 seroconversion occurred in both children and adult recipients. None of the seroconversion events was related to the source of the donor organ. These findings suggest that HHV-8 infection is not uncommon among both adult and children transplant recipients and that viral infection may be acquired from an outside source other than the transplanted organ.     

HIV,syphilis and heterosexual bridging among Peruvian men who have sex with men

OBJECTIVES: To determine prevalence of and risk factors associated with HIV and syphilis seropositivity and estimate incidence of HIV infection among Peruvian men who have sex with men (MSM) and characterize behaviors of men who report sex with both men and women ('bridgers'). DESIGN: Cross-sectional study of MSM in Lima, Peru. METHODS: Four-hundred and fifty-one MSM (of whom 442 responded to the question regarding sexual orientation) recruited through street outreach. Each was interviewed and underwent serologic testing for syphilis and HIV, including the less sensitive enzyme immunoassay test to estimate HIV incidence. RESULTS: Overall, HIV and syphilis prevalence were 18.5% and 16.0%, respectively, with highest prevalence among cross-dressers (33.3% and 51.1%, respectively). The estimated overall HIV seroincidence was 11.2% per year (95% confidence interval, 4.8-23.6). Overall, 47.1% of men reported ever having sex with a woman: 78.6% of men self-identifying as heterosexuals, 85.1% of bisexuals, 35.5% of homosexuals, and 12.5% of cross-dressers. Of these, 26.5% were 'bridgers', of whom 55% reported two or more female partners during the last year. 'Bridgers' were less likely to have always used condoms during the past year for vaginal sex (17%) than for insertive anal sex with men (25.5%). CONCLUSIONS: Among MSM in Peru, HIV and syphilis prevalence and HIV incidence were high, especially among cross-dressers. The high prevalence of bisexuality and low rates of consistent condom use, especially with female sexual partners indicates potential HIV transmission into the heterosexual population.     

Repeated measures study of human herpesvirus 8 (HHV-8) DNA and antibodies in men seropositive for both HHV-8 and HIV

OBJECTIVE: To study the natural history and pathogenesis of human herpesvirus 8 (HHV-8) infection in HHV-8-seropositive, immunosuppressed men. DESIGN: Longitudinal study of 87 HHV-8- and HIV-seropositive men [42 with Kaposi's sarcoma (KS)] during four visits over a 2 month period. METHODS:: Patients provided oral fluid and blood. HHV-8 antibody titers were measured with peptide-based enzyme-linked immunosorbent assays (ELISA) for ORF65 and K8.1; HHV-8 DNA was detected with polymerase chain reaction ELISA. RESULTS: HHV-8 DNA was present in oral fluid or peripheral blood mononuclear cells (PBMC) at one or more of the four visits in 71% of men with KS and 56% of men without KS. The strongest correlate of HHV-8 DNA in PBMC was the presence of KS [odds ratio (OR), 8.7; 95% confidence interval (CI), 3.4-22]. Detection of HHV-8 DNA in oral fluid or PBMC was often intermittent, but individuals who shed virus at one time point were more likely to shed at other times. Some men had incomplete epitope recognition in their anti-HHV-8 antibody response. High antibody titers were associated with the absence of circulating HHV-8, particularly for the ORF65 seroassay (OR, 0.16; 95% CI, 0.05-0.51). CONCLUSIONS: Among HHV-8 seropositive men, circulating virus is common even in the absence of disease. The link between KS and HHV-8 DNA in PBMC suggests that anti-herpes drugs may impede KS development or progression. Seroassays should target multiple epitopes to achieve maximal sensitivity. HHV-8 replication may be limited by high antibody titers or other immune function for which antibodies are a marker.