Besides HIV status and sexual preference, age of first sex was also associated with male HBV infection. HBV infection rates were higher for males who had had anal or vaginal sex before 13 years of age (P = 0.049; odds ratio [OR], 5.4; 95% CI, 1.1‐26.9). For females infected with HBV, only number of lifetime partners was significantly associated with HBV infection; those who had more than 10 partners had a higher risk of infection (P = 0.02; OR, 2.4; 95% CI, 1.2‐5.1).
For males infected with HCMV, sexual preference and HIV status were associated significantly with HCMV infection. Homosexual or bisexual males had a higher infection rate (OR, 5.32; 95% CI, 1.2‐9.5), as did subjects who were HIV infected (OR, 3.10; 95% CI, 1.1‐8.8). For females, only HIV status was associated with HCMV infection (P = 0.003). Subjects who were HIV infected were more likely to be HCMV positive (OR, 2.4; 95% CI, 1.3‐4.3).
We report the results of a seroprevalence and risk‐factor analysis for HBV, HCV, and HCMV infections in a unique cohort of HIV‐infected and high‐risk, HIV‐negative adolescents. Aside from the high seroprevalence rates for these viral infections, we have substantiated previous findings of the association of sexual‐activity behaviors and increased risk for HCMV and HBV acquisition.4–10 These data support the need for continuing primary and secondary prevention programs in adolescents to reduce the transmission of these viruses, and the need for clinical screening and treatment for HBV and HCMV in adolescents.
The seroprevalence rates of HBcAb in this cohort are among the highest reported rates for adolescents in areas of low HBV endemicity,5 including subpopulations of similar racial composition. These rates approximate the reported rates for high‐risk ethnic or immigrant groups within the United States; however, this was not a significant risk factor in our analysis because only 13 mothers of the subjects were born in known endemic areas. In the female cohort in the multivariate analysis, the only significant risk factor among those analyzed that was associated with HBV seropositivity was having more than 10 lifetime sexual partners. Previous studies have identified the number of partners, both lifetime and recent, as risk factors associated with HBV seropositivity among heterosexuals.4
In our sample of males, all of the HBV infections were found in HIV‐positive, homosexual or bisexual males. The HBV seropositive rate in the HIV‐positive homosexual male cohort was 35% (14 of 40 subjects). Previous studies have found HBV seroprevalence to be as high as 61.5% among older male homosexuals.6 In that study, risk factors that were associated with HBV seropositivity were duration of regular homosexual activity, number of nonsteady partners during the past 4 months, anal‐genital or oral‐anal intercourse, and rectal douching. Our finding of an association of earlier sexual debut with HBV seropositivity is consistent with the primary mode of transmission being related to sexual behavior. The high HBV chronic‐carrier rates among HIV infected individuals and the high‐risk sexual practices make these male homosexual youth who practice unsafe sex with high‐risk partners particularly vulnerable to these coinfections.
In the cohort described, the overall rate of HIV infected subjects with HBV infections who had evidence of active replicating HBV is 21% (15% among the females and 36% among the male cohort). This is the first description of these rates in an HIV‐infected adolescents who appear to have acquired both HIV and HBV through sexual activity. Given the cross‐sectional design of this study, we cannot define any of our subjects with active HBV infections as chronic carriers; however, based on other studies,24,25 we would project that the subjects reported here with active infections are likely to be chronic carriers. There is an extensive literature on the chronic‐carrier state of HBV in older male homosexuals infected with HIV. These studies demonstrated increased persistence of HBV24,26 and more active HBV replication in HIV‐infected persons compared with HIV‐uninfected persons.25,27 However, there is no evidence that hepatic necrosis or disease due to HBV progresses more rapidly in HIV‐infected persons, and the evidence regarding the effect of active HBV infections on HIV disease progression is not consistent.28,29 Overall, our data have implications in the area of public health because these youth with active infections are more likely to transmit HBV than they are to be individually affected by HBV.
The seroprevalence of HCMV infection in the female cohort reported here (69.8%) is similar to that seen in a racially similar adolescent population in an STD clinic (68%),9 in a lower‐socioeconomic stratified group (67%),8 and in a lower‐income adolescent group in an STD clinic (79%).7 In our cohort, there was a higher seroprevalence of HCMV in the HIV‐infected female group compared with the HIV‐uninfected group (78% versus 61%, P = 0.003). The lack of an association of sexual‐activity variables other than HIV infection with HCMV seroprevalence in this study might be accounted for either by the high background seroprevalence rates in the total cohort or by the high‐risk sexual behaviors of the cohort as a whole. This is one of the first studies that found no association between higher HCMV seroprevalence and black racial background, which may reflect more similarity in the overall socioeconomic status of different racial groups in our cohort than that of previous studies.
The HCMV seroprevalence in the male cohort reported here (69.7%) is considerably higher than that reported in previous seroepidemiologic studies,11 but is lower than the rates seen in older male homosexuals in STD clinics (94%).30 In univariate analyses, multiple sexual‐practice risk factors associated with HCMV seropositivity include receptive and insertive anal‐genital intercourse, younger age at sexual debut, and higher number of lifetime partners. However, in a multivariate analysis model, only a homosexual or bisexual sexual orientation and HIV seropositivity remained significantly associated with HCMV infection, suggesting that the high‐risk sexual activity variables are associated with these two significant risk factors in our cohort. This finding is also similar to the HBV analysis, and suggests that these young homosexual males are being exposed to high‐risk partners.
The overall prevalence of HCV infection in this adolescent cohort (1.6%) is higher than that reported for adolescents as a whole (0.4%), but similar to the rate reported for non‐Hispanic black adolescents (1.2%).29 Given the low rate of admitted intravenous drug use in this cohort, which was substantiated by prospective urine drug screening (data not shown), the HCV infections most likely represent sexual transmission. Sexual transmission of HCV most likely occurs, but this transmission is inefficient compared with HCMV, HBV, and HIV. It is estimated that 20% of acute HCV is associated with high‐risk sexual behavior, whereas 60% is associated with high‐risk drug‐taking behavior (10% cannot be accounted for).31
Interpretation of specific relationships between the risk factors examined and the risk of acquiring HCV, HBV, or HCMV reported in this study should be tempered by the cross‐sectional design and the retrospective data collection of several risk‐factor variables. However, the consistent finding of the association of various sexual risk behaviors and seropositivity is consistent with other studies that suggest the sexual transmission of these viruses. The unique nature of this cohort, including the selection of HIV‐negative subjects for their histories of high‐risk behaviors and the limited number of adolescents with drug‐injecting behaviors, may limit the overall ability to generalize from these data. However, the risk of acquisition of any of these viruses through risky sexual behaviors is clear.
In conclusion, we have demonstrated the high seroprevalence of HBV, HCMV, and HCV in this unique cohort of HIV‐infected and HIV‐uninfected high‐risk adolescents. These data support the risks of acquisition of these infections through sexual behaviors in both male and female adolescents, but particularly in males with same‐sex sexual orientation. In addition, the high rates of evidence of active HBV infection in both male and female HIV‐infected cohorts indicate a higher risk for secondary transmission of HBV. These data reinforce the need for continuing development and application of both primary and secondary prevention programs directed at adolescents to reduce the acquisition and transmission of these viruses, and the need for screening and treatment of HBV and HCMV.
1. Hollinger FB. Hepatitis B virus. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. Philadelphia: Lippincott-Raven, 1995; 2738–2807.
2. Houghton M. Hepatitis C virus. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. Philadelphia: Lippincott-Raven, 1995; 1035–1058.
3. Britt WJ, Alford CA. Cytomegalovirus. In: Fields BN, Knipe DM, Howley PM, eds. Fields Virology. Philadelphia: Lippincott-Raven. 1995; 2493–2524.
4. Alter MJ, Alexander PJ, Kramer E, et al. Importance of heterosexual activity in the transmission of hepatitis B and non-A, non-B hepatitis. JAMA 1989; 262:1201–1205.
5. Margolis MJ, Handler SC. Hepatitis B: evolving epidemiology and implications for control. Semin Liver Dis 1991; 11:81–92.
6. Schreeder SE, Hadler SC, Berquist KR, et al. Hepatitis B in homosexual men: prevalence of infection and factors related to transmission. J Infect Dis 1982; 146:7–15.
7. Chandler SH, Wentworth BB, Gutman LT, Wiesner PJ, Alexander ER, Handsfield HH. The epidemiology of cytomegaloviral infection in women attending a sexually transmitted disease clinic. J Infect Dis 1985; 152:597–605.
8. Davis JA, Garvin S. Cytomegalovirus infection: a seroepidemiologic comparison of nuns and women from a venereal disease clinic. Am J Epidemol 1975; 102:327–330.
9. Sohn MK, Balcarok KB, Cloud GA, Pass RF. Cytomegalovirus infection in sexually active adolescents. J Infect Dis 1991; 163:460–463.
10. Stango G, Pass RF, Britt WJ, Alford CA. Factors associated with primary cytomegalovirus infection during pregnancy. J Med Virol 1984; 13:347–353.
11. Wentworth ER. Seroepidemiology of infections due to members of the herpesvirus group. Am J Epidemol 1971; 94:496–507.
12. McQuillan G, Coleman PJ, Kruszon-Moran D, Moyer LA, Lambert SB, Margolis HS. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976–1994. Am J Public Health 1999; 89:14–18.
13. Spector SA, Wong R, Hsia M, Pilcher M, Stempien J. Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients. J Clin Invest 1998; 101:497–502.
14. Spector SA, Hsia K, Crager M, Pilcher M, Cabral S, Stempien M. Cytomegalovirus (CMV) DNA load is an independent predictor of CMV disease and survival in advanced AIDS. J Virol 1999; 73:7027–7030.
15. Sever JL, Coinfection with herpesviruses in young children of HIV-infected women. Pediatr AIDS HIV Infec 1995; 2:75–82.
16. Kovacs A, Schluchter M, Easley K, et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. N Engl J Med 1999; 341:77–84.
17. Rogers AS, Futterman D, Moscicki AB, Wilson C, Ellenberg J, Vermund SH. The REACH project of the adolescent medicine HIV/AIDS research network: design, methods, and selected characteristics of participants. J Adolesc Health 1998; 22:300–311.
18. Rogers AS, Schwarz DF, Weissman, G, English A. A case study in adolescent participation in clinical research: eleven clinical sites, one common protocol, and eleven IRBs. Rev Hum Subjects Res 1999; 21:6–10.
19. Fienberg SE. The Analysis of Cross-Classified Data. Cambridge: MIT Press, 1977.
20. Mehta CR, Patel NR. A network algorithm for performing Fisher's exact test in contingency tables. J Am Stat Assoc 1987; 78:427–434.
21. Agresti A. Categorical Data Analysis. New York: John Wiley & Sons, 1990.
22. Hosmer DW, Lemesshow S. Applied Logistic Regression. New York: John Wiley & Sons, 1989.
23. Clark LA, Pregibon D. Tree-based models. In: Chambers JM, Hastie TJ, eds. Statistical Models. Pacific Grove: Wadsworth & Brooks, 1992:377–417.
24. Hadler SC, O'Malley PM, Altman NL, et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 1991; 163:454–459.
25. Bodsworth ND, Nightingale BN. The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men. J Infect Dis 1989; 160:577–582.
26. Bodsworth NJ, Cooper DA, Donovan B. The influence of human immunodeficiency virus type 1 on the development of the hepatitis B carrier state. J Infect Dis 1991; 163:1138–1140.
27. Krogsgaard KL, Nielsen JO, Andersson P, et al. The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers. Hepatology 1987; 7:37–41.
28. Gilson RJ, Beecham MR, Ross E, et al. Interactions between HIV and hepatitis B virus in homosexual men: effects on the natural history of infection. AIDS 1997; 11:597–606.
29. Alter MJ, Kriszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA, Kaslow RA, Margolia HS. The prevalence of hepatitis C virus infection in the United States, 1988–1994. N Engl J Med 1999; 341:556–562.
30. Drew WL, Miner RC, Sands M, Ketterer B. Prevalence of cytomegalovirus infection in homosexual men. J Infect Dis 1981; 143:188–192.
31. Alter MJ. Epidemiology of hepatitis C. Hepatology 1997; 26:62S-65S.
The following investigators, listed in order of the numbers of subjects enrolled, participated in this study: University of Miami: L. Friedman, L. Pall, D. Maturo, A. Pasquale; Montefiore Medical Center: D. Futterman, D. Monte, M. Alovera‐DeBellis, N. Hoffman, S. Jackson; University of Pennsylvania and the Children's Hospital of Philadelphia: B. Rudy, D. Schwarz; Children's Hospital of Philadelphia: M. Tanney, A. Feldman; Children's Hospital of Los Angeles: M. Belzer, D. Tucker, C. Kallal, D. Fuchs; Tulane Medical Center: S.E. Abdalian, L. Green, M. Ales, L. Wenthold; Children's National Medical Center: L. J. D'Angelo, C. Trexler, C. Townsend‐Akpan, R. Hagler, J.A. Morrissy; University of Maryland: L. Peralta, C. Ryder, S. Miller; Cook County Hospital/University of Chicago: L. Henry‐Reid, R. Camacho, D. Johnson; Children's Hospital, Birmingham: M. Sturdevant, A. Howell, J.E. Johnson; Children=s Diagnostic and Treatment Center: A. Puga, D. Cruz, P. McLendon; Emory University: M. Sawyer, J. Tigner; St. Jude Children's Research Hospital: P. Flynn, K. Lett, J. Doss; Mt. Sinai Medical Center: L. Levin, M. Geiger; University of Medicine and Dentistry of New Jersey: P. Stanford, F. Briggs; SUNY Health Science Center at Brooklyn: J. Birnbaum, M. Ramnarine. The following investigators have been responsible for the basic science agenda: C. Holland, Center for Virology, Immunology, and Infectious Disease, Children's Research Institute, Children's National Medical Center; A.B. Moscicki, University of California at San Francisco; D.A. Murphy, University of California at Los Angeles; S.H. Vermund, University of Alabama at Birmingham; P. Crowley‐Nowick, The Fearing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; S. D. Douglas, University of Pennsylvania and the Children's Hospital of Philadelphia. Network operations and analytic support are provided by C.M. Wilson, C. Partlow at University of Alabama; B. Hobbs, J. H. Ellenberg, L. Paolinelli, S. J. Durako, L. Muenz, R. Mitchell, K. Clingan, P. Ohan, V. Junankar, O. Leytush, A. Bennett, M. Rakheja, C. Xue, Y. Ma, J. Houser at Westat, Inc. Cited Here...