A total of 342 blood specimens were available for HHV-8 testing, and 110 (32.2%) were positive. The seroprevalence of HHV-8 was higher in MSM (35.0%) than in heterosexual men (26.5%), although this was not statistically significant (P = 0.13). Demographic information, sexual behaviors, parenteral exposures, and laboratory values are shown in Tables 1, 2, 3, and 4.
Correlates of HHV-8 Infection
Hepatitis B seropositivity (odds ratio [OR], 2.50; 95% confidence interval [CI], 1.51–4.13) was significantly correlated with HHV-8-seropositive status in the univariate analysis (P <0.001). No statistically significant relationships were found between HHV-8 serostatus and any demographic or sexual history variables, including number of lifetime sexual partners, history of STIs, receptive oral or anal intercourse, HSV-2 seropositivity, reporting sex with a known HIV-infected sexual partner, bleeding or condom use during sexual activities. Furthermore, there was no association of HHV-8 seropositivity and injection drug use, other drug use, including nitrates, a history of tattoos or body piercing, needlestick injuries, or hepatitis C seropositivity. In a multivariate analysis adjusted for age, ethnicity, education, HIV-infected sexual partner, hepatitis B serostatus, and HSV-2 serostatus, HHV-8 seropositivity was associated with hepatitis B (OR, 2.44; 95% CI, 1.45–4.11); blacks had a significantly lower rate of HHV-8 seropositivity than whites (OR, 0.55; 95% CI, 0.33–0.93;Table 5). There was no evidence of confounding between variables in the multivariate model. Interactions between sexual orientation and ethnicity, sexual orientation and oral sex, sexual orientation and anal sex, and sexual orientation and self-reported bleeding were assessed with no statistically significant findings.
Because sexual behaviors that might predispose to HHV-8 infection varied by sexual preference in our univariate analyses and previous studies, the participants were divided into heterosexual and MSM groups (Table 6). Among MSM, both hepatitis B (OR, 2.52; 95% CI, 1.33–4.78) and HSV-2 (OR, 2.64; 95% CI, 1.42-4.91) were strongly associated with HHV-8 in univariate analyses. A history of STIs other than HSV-2 was associated with an elevated risk of HHV-8 infection, although this finding was not statistically significant (OR, 1.68; 95% CI, 0.92-3.08). In a multivariate model adjusted for age, STIs during lifetime, hepatitis B, and HSV-2, both HSV-2 (OR, 2.60; 95% CI, 1.38-4.89) and hepatitis B (OR, 2.17; 95% CI, 1.10-4.29) remained significantly related to HHV-8 in MSM. The correlates of HHV-8 infection were different between heterosexual men and MSM. Univariate analyses among heterosexuals showed that blacks (OR, 0.32; 95% CI, 0.13-0.75) and married persons were less likely to have serologic evidence of HHV-8 infection (OR, 0.43; 95% CI, 0.18-0.99), whereas persons reporting a higher level of education (OR, 4.67; 95% CI, 1.31-16.62) were more likely to be HHV-8-seropositive. In the multivariate analysis adjusted for age, ethnicity, marital status, and education, being married as compared with being single (OR, 0.38; 95% CI, 0.15-0.97) and black ethnicity (OR, 0.30; 95% CI, 0.11-0.79) were associated with lower HHV-8 seroprevalence. Among heterosexuals, a history of STIs, including HSV-2 and hepatitis B serostatus, was not related to HHV-8 infection.
We identified a high seroprevalence (32%) of HHV-8 infection among recently HIV-infected U.S. military men. Our study population of recently HIV-infected military men was identified by periodic HIV screening with a mean length of HIV infection at study enrollment of 11 months. This is the first study to examine HHV-8 seroprevalence and its correlates among U.S. military personnel.
Although the study population included approximately equal numbers of heterosexuals and MSM, the overall seroprevalence of this group is similar to that found in other studies among HIV-infected MSM. 2-6 The prevalence of HHV-8 infection among this cohort of U.S. men reporting heterosexual behavior is significantly higher than that reported in previous studies, although, to our knowledge, no previous studies have looked at HHV-8 seroprevalence among men who acquired HIV through heterosexual sex. HHV-8 infection among this group was 5 to 25 times that seen in random U.S. blood donors, suggesting that there might be common risk factors for the acquisition of HIV and HHV-8 in this population. 1
The risk factors for HHV-8 infection differed between MSM and heterosexual men, despite their being from the same general population of HIV-infected military personnel. Among MSM, both hepatitis B and HSV-2 were associated with HHV-8 seropositivity, and no association was found between hepatitis C and HHV-8. These data, consistent with previous studies, 5-7 suggest that HHV-8 is likely to be transmitted by sexual activity among MSM. Although our study examined a wide variety of sexual behaviors, we did not identify any specific sexual behavior, including anal sex, oral sex, bleeding during sex, or having an HIV-infected partner, that was associated with HHV-8 infection. Of note, our study did not examine the frequency of oral-receptive sex or kissing in relation to HHV-8; a prior study found that exposure to saliva is associated with HHV-8 infection. 8 Among heterosexuals, hepatitis B and HSV-2 were not associated with HHV-8 seropositivity. Smith et al. showed that in MSM, HHV-8 was associated with STIs, but found that in heterosexual men, there was no evidence for sexual transmission. 5 Taken together, these findings suggest that the mode of transmission of HHV-8 might be somewhat different between MSM and heterosexual men. Salivary transmission of HHV-8 could conceivably reconcile the disparities in correlates of infection between diverse populations.
We found that blacks had a lower seroprevalence of HHV-8 than whites. The blacks in our population were more likely to be heterosexual and were less likely to report nitrate use, anal intercourse, or sex with a known HIV-infected partner. However, when we examined only heterosexuals, the negative association between black ethnicity and HHV-8 remained. A positive association between blacks and HHV-8 has been noted in women 2,12; however, no association has previously been noted in men. 4,13,14 The reason that heterosexual black U.S. military men have a lower rate of HHV-8 than whites is unclear. Black heterosexuals in our study reported more high-risk sexual behaviors and had a higher rate of hepatitis B and HSV-2 seropositivity than whites; these findings are supported by other studies. 15-17 HHV-8 seroprevalence varies significantly among well-defined demographic groups. In the United States, infection rates are highest among MSM, a group that is largely comprised of whites. Blacks in the military might lack exposure to persons from demographic groups that are likely to be infected with HHV-8.
The relationship between marital status and HHV-8 infection has not previously been reported in the published literature. The reason that heterosexual men who are married (as compared with single persons) have a lower seroprevalence of HHV-8 is unknown, but could be related to fewer lifetime or high-risk partners.
There were a number of limitations to our study. Like with any study that assesses exposure status through the use of a self-reported study instrument, the validity of survey responses could not be verified. However, although the official military policy against drug use or homosexual behavior could bias the responses to our questionnaire, a substantial number of men did report MSM behavior and drug use. The low reported rate of injection drug use is supported by the lack of hepatitis C seropositivity in our group. In addition to questionnaire data regarding risk factors, biologic outcomes to determine sexual exposures such as HSV-2, hepatitis B, and syphilis serologies were also measured. This study was designed to assess risk factors associated with HIV seroconversion; therefore, it might have failed to collect specific correlates of HHV-8 infection. In addition, as a result of the cross-sectional study design, we could not evaluate the temporal relationship between a specific behavior and acquisition of HHV-8 infection. Although several specific risk behaviors were assessed, the duration and frequency of these behaviors were not ascertained. Future studies should focus on incident risk factors with quantitative questions regarding potential risk factors.
Based on the findings of this study, HHV-8 is a commonly acquired infection among both MSM and heterosexual men with HIV infection; this suggests that behaviors that place men at risk for HIV might also be associated with acquisition of HHV-8. The U.S. military population is not at increased risk for HHV-8 in general because HHV-8 seroprevalence rates in our population were similar to other studies examining HIV-infected persons. HHV-8 seropositivity is highly associated with STIs such as HSV-2 and hepatitis B in MSM but not in heterosexuals. Safer sexual practices are recommended to reduce the incidence of HHV-8 infections in HIV-infected MSM 18; it is unclear whether such strategies would be efficacious in heterosexual men, because sexual risk factors were not correlated with HHV-8 infection in this study. Furthermore, the high rate of HHV-8 infection among HIV-positive heterosexual men and the low rate of infection among blacks suggests that much has yet to be learned about the seroprevalence of HHV-8 infection among persons not traditionally considered to be at high risk for the development of Kaposi's sarcoma. Studies aimed at determining the correlates of incident HHV-8 infection among broader populations of HIV-infected individuals are now warranted and will help to define the mode of HHV-8 transmission in areas where the virus is not endemic.
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