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High Rates of Viral Infections & HCV and For Risk Factors Among HIV-Infected and High-Risk HIV-Uninfected Women
  Cynthia Stover (Emory University; CDC) and colleagues from the HIV Epidemiology research Study group reported in the may 1 issue of the Journal for Infectious Diseases (2003;187:1388-1396) that women with HIV tend to be in certain high risk groups for other viral infections. The researchers discuss their findings that HIV-infected women tend to have high rates of viral infections in addition to HIV. Prevalences of viral infections were particularly high for HIV-infected women. While HIV is a real problem in undeveloped countries, HIV is an worsening problem in the US among certain HIV-infected populations; and, as this study demonstrates the problem rages among HIV-infected women and in high-risk female populations. It is also clear from this study that rates of hepatitis C and B infection among HIV-infected women is very high.
"..HCV seroprevalence was 89.7% among injection drug users, compared with 10.5% among noninjection drug users.. Women in HERS who did not inject drugs may have acquired HCV sexually.. The 10.5% HCV seroprevalence among noninjection drug users is much higher than that in the general population, which might be explained by higher numbers of sex partners and a higher prevalence of HCV infection in sex partners among women included in HERS…...seroprevalence for HBV were 76% among IDUs and 21% among women who were not IDUs…. among persons with acute hepatitis B in the overall US population, sexual exposures account for most HBV transmission—HBV is more easily transmissible by sex than HCV.. Even after we controlled for confounding, persons infected with one HSV type were less likely to be infected with the other type, which suggests that antibodies against one infection may protect against the other. Because HSV-1 infection usually occurs first via nonsexual routes in childhood, antibodies to HSV-1 may be partially protective against HSV-2. Several other studies also have found a protective effect, but in a large clinical trial and a national survey, no such effect was found.
In the United States, 30,000-41,000 new HIV infections occur annually, and the burden of HIV infection is borne increasingly by women. In 2001, 129,000 AIDS cases were reported among women, compared with 30,000-45,000 in 1984. In 1999, 18%-23% of all persons with AIDS in the United States were women, compared with 7% in 1986.
In parallel with the HIV epidemic, 15 million persons in the United States annually acquire other sexually transmitted diseases. Although the incidence of bacterial infections such as syphilis and gonorrhea has decreased, the incidence of viral sexually transmitted infections has increased considerably in recent years. Viral infections associated with injection drug use (IDU) also represent a major public health problem. For example, an estimated 30,00035,000 new hepatitis C virus (HCV) infections occur annually in the United States. Viral infections have always been a source of substantial disease burden, but the HIV epidemic has created a population of immunosuppressed persons in whom the clinical manifestations of these infections may be even more severe.
Among the clinically important viral infections are several that can persist within an individual. They include cytomegalovirus (CMV), hepatitis B virus (HBV), HCV, human herpesvirus 8 (HHV-8), human papillomavirus (HPV), and herpes simplex virus (HSV) types 1 and 2. CMV is a leading cause of brain damage and hearing loss in children and is a major opportunistic infection among persons infected with HIV, in whom it often causes blindness or disseminated disease. HBV and HCV cause chronic liver disease, which can lead to cirrhosis and liver cancer, and liver failure due to HCV infection is the most common reason for liver transplantation. HHV-8 is essential to the development of Kaposi sarcoma, an AIDS-associated cancer. HPV, the most common sexually transmitted viral infection in the United States, can cause cervical cancer. HSV-1 and HSV-2 cause recurrent ulcerative lesions that may facilitate HIV transmission.
Although much research has been done on HIV and opportunistic infections in men, these infections and their sequelae are not as well studied among women. The prevalence and long-term effects of certain infections may differ between women and men. In addition, many of the HIV risk factors for men who have sex with men (e.g., unprotected receptive anal sex and intercourse at bathhouses or sex clubs) are less common among women, yet women are acquiring HIV and other sexually transmitted infections at increasing rates, which suggests that they have risk factors for infection that differ from those for men.
The goal of this study was to provide robust estimates of viral infection prevalences in an understudied, immunocompromised population and to determine the primary risk factors for infection. To achieve this goal, we examined 7 viral infections among HIV-infected and high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS). HERS followed up a cohort of women over a period of 6 years (1993-1999) to examine the biological, psychological, and social effects of HIV infection on women's health. The study enrolled 871 HIV-infected and 439 demographically matched (i.e., by age, race/ethnicity, and study site) HIV-uninfected women aged 16-55 years in 4 US cities.
By design, approximately two-thirds (66.5%) of the women in the study were infected with HIV, and more than one-half (58.5%) reported having injected drugs. Black was the dominant racial group (58.2%), followed by white (24.2%) and other (17.6%). Almost one-half of the women (42.7%) had less than high school education, and approximately three-fourths (72.6%) had an annual income of <$12,000. Two-thirds (65.8%) reported having smoked crack cocaine. Approximately one-fourth of the women (28.1%) reported having had >20 sex partners in their lifetimes, and 41.1% reported having had commercial sex. One-third (35.7%) of the women began having sex before they were 15 years old. Nearly all of the women (87.9%) reported having smoked cigarettes.
Because HERS used a variety of recruitment modalities in 4 different cities, these women are reasonably representative of the US population of HIV-infected women without AIDS and HIV-uninfected women at high risk for HIV infection.
Viruses that can persist in the host are of special concern in immunocompromised populations. Among 871 human immunodeficiency virus (HIV) infected and 439 high-risk HIV-uninfected women, seroprevalences of cytomegalovirus, hepatitis B virus, hepatitis C virus, and herpes simplex virus types 1 and 2 and prevalence of human papillomavirus DNA in cervicovaginal lavage fluids were all >50% and were 230 times higher than prevalences in the general population. Prevalences were highest among HIV-infected women, of whom 44.2% had 5 other infections, and were relatively high even among the youngest women (age 1625 years). In multivariate analyses, viral infections were independently associated not only with behaviors such as injection drug use and commercial sex but also with low income, low levels of education, and black race. Disadvantaged women and women who engage in high-risk behaviors are more likely to be coinfected with HIV and other viruses and, thus, may be at high risk of serious disease sequelae.
HIV infection was significantly associated with having each individual infection, except HSV-1. The association between HIV and HPV was especially strong (OR, 4.7; 95% confidence interval [CI], 3.66.1). HIV infection was also significantly associated with having multiple infections. Among HIV-infected women, 70.1% had 4 other infections, and 44.2% had 5 other infections; among HIV-uninfected women, 48.3% had 4 other infections, and 25.3% had 5 other infections.
60% of the women were HCV+; 59% were HBV+; 94% were CMV+; 63% were HPV+; 74% were HSV-1 positive and 67% were HSV-2 positive. Both blacks and whites had high rates of these diseases. Regarding HCV, 55% of the women in New York were HCV+, 45% of the women in Detroit were HCV+, 68% of the women in Baltimore were HCV+, and 56% of the women in Providence, RI were HCV+. Similar rates of HBV positivity were seen.
Across different age groups of HIV-infected women, the prevalence of most infections remained constant. However, the seroprevalences of HBV and HCV increased with age and were nearly 4-fold higher among the oldest women than among the youngest. Among HIV-uninfected women, seroprevalence of HBV, HCV, and HSV-2 increased significantly (P < .001) with age. In the same group, HPV DNA was detected significantly less often in the genital tracts of older women.
In univariate analyses, CMV was strongly associated with black race, and HBV and HSV-2 were moderately strongly associated with black race. CMV, HBV, HCV, HSV-1, and HSV-2 were associated with less education, and CMV, HBV, HCV, and HSV-1 were associated with lower income. IDU was highly correlated with HCV and HBV infections and, to a lesser extent, with CMV and HHV-8. Among pairs of infections, findings of note included a strong association between HBV and HCV and an inverse association between HSV-1 and HSV-2.
Most univariate associations persisted in multivariate models. Significant positive associations included those of CMV with black race (adjusted OR, 2.8; 95% CI, 1.55.4); of HBV and HCV with IDU (for HBV, adjusted OR, 10.8, and 95% CI, 7.814.9; for HCV, adjusted OR, 63.4, and 95% CI, 41.297.7); and of HPV with HIV infection (adjusted OR, 4.2; 95% CI, 3.15.6). The negative association remained between HSV-2 and HSV-1 infection (adjusted OR, 0.6; 95% CI, 0.40.9). Controlling for HIV, age, race, site, IDU, and commercial sex attenuated the associations between socioeconomic factors and viral infections. However, lower level of education was still associated with CMV (adjusted OR, 1.6; 95% CI, 0.92.7), HBV (adjusted OR, 1.4; 95% CI, 1.01.9), HCV (adjusted OR, 1.5; 95% CI, 1.02.3), HSV-1 (adjusted OR, 1.7; 95% CI, 1.22.2), and HSV-2 (adjusted OR, 1.6; 95% CI, 1.22.1). Similarly, lower income level remained associated with HCV (adjusted OR, 1.7; 95% CI, 1.12.6) and HSV-1 (adjusted OR, 1.6; 95% CI, 1.22.2). HIV seropositivity remained associated with having multiple viral infections, even after we controlled for demographic and behavioral variables (for 4 infections, adjusted OR, 2.4, and 95% CI, 1.93.1; for 5 infections, adjusted OR, 2.4, and 95% CI, 1.83.2).
We found that HIV was associated with multiple infections (e.g., 4 and 5 infections) even after we controlled for behavioral variables. This result suggests that, as has been shown for single infections, HIV may facilitate the transmission of other viruses, and other viruses may facilitate the transmission of HIV. For example, genital HSV-2 lesions can facilitate transmission of HIV or other sexually transmitted agents. Conversely, in HIV-infected persons, HSV-2 lesions occur more frequently and tend to last longer, thus increasing the chance that an individual will acquire or transmit additional infections.
HBV was associated with variables denoting high sexual risk in the HERS population, but most HBV infections were attributable to IDU. HBV seroprevalence was much higher among women who injected drugs than among women who did not (76.7% vs. 21.1%), and IDU was a stronger multivariate risk factor for HBV than was commercial sex (OR, 10.8 vs. 1.6). These results are consistent with the higher efficiency of bloodborne virus transmission by direct percutaneous exposures to blood than by sexual exposures; however, the high proportion of HBV infections attributable to IDU is also the result of the selection of a high proportion of injection drug users for participation in HERS. Among persons with acute hepatitis B in the overall US population, sexual exposures account for most HBV transmission, because persons who inject drugs represent only a small fraction of the total population.
Socioeconomic factors, such as lower level of education and income, were associated with all 7 viral infections. The strength of these associations was reduced after we controlled for behavioral variables, but, similar to previous reports for HBV and HCV, several viral infections were independently associated with low socioeconomic level.
We found age-related increases in prevalence for infections that were predominantly acquired through injection drug use (i.e., HBV and HCV). In contrast, there was an age-related decrease in HPV DNA prevalence among HIV-uninfected women, a decrease that has been noted by others. In such women, HPV DNA is a marker for recent infection and thus is found more often in younger women, because they tend to have a higher prevalence of risky sexual behaviors. HPV DNA prevalence among HIV-infected women did not decrease with increased age, a finding that is consistent with previous reports suggesting that viral persistence is associated with immunodeficiency. Despite varying age trends, most infections were highly prevalent, even in the youngest group, which suggests that behavioral interventions targeting sexual activity and IDU need to begin at a young age.
In conclusion, multiple viral infections are a common problem among women with or at risk for HIV infection. Although HIV infection and risky individual behavior are of key importance in the acquisition of viral infections, socioeconomic factors may also play an important role. We identified the scope of infection in this population, but a better understanding of consequences of viral diseases is still needed. Many of these infections have serious disease sequelae in immunocompromised persons, and therefore, as the number of women infected with HIV continues to increase, the number of women with serious sequelae from viral infections likely will increase as well.
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