SEXUAL TRANSMISSION OF HEPATITIS C virus (HCV) has remained a subject of controversy. The prevalence of HCV is much higher in HIV-infected individuals in contrast to the prevalence of HIV in HCV-infected individuals. These observations can be explained in part as a result of a predominant role for sexual transmission of HIV and a parenteral route for HCV transmission.1
Recently, outbreaks of acute HCV have been reported in highly promiscuous men who have sex with men (MSM) in Europe. Investigators from a Swiss cohort reported 22 episodes of acute HCV in 14 homosexual and 8 heterosexual men (P <0.001) who had previously tested negative for HCV. In Paris, 10 of 12 cases of genotype 4D HCV infection having a closely related HCV genome were identified in homosexual MSM.2–5 One study reported a higher prevalence of HCV among MSM as compared with a group of blood donors. A multivariate analysis showed that this finding could be accounted for by a history of intravenous drug use (IVDU).6 Although these reports are tantalizing, sequence homology of HCV clones has its own limitations and does not definitively confirm transmission of HCV from one individual to another.7
In contrast to these recent reports, many epidemiologic studies have failed to show an association between sexual risk factors and HCV infection. Heterosexual monogamous couples who have been followed prospectively have failed to support sexual transmission of HCV.8 In addition, the prevalence of HCV among MSM has not been found to be different from that of heterosexual men despite the fact that MSM have higher rates of sexually transmitted diseases and more numerous sexual partners.9 Finally, a prospective cohort study of MSM (40.3% having ≥50 casual partners) documented a strong association between HCV infection and IVDU, but not between HCV and sexual orientation.10
The epidemiologic surveys used in many studies presume that the information obtained from a subject using a questionnaire is accurate. Specifically for HCV transmission, nondisclosure of IVDU by study participants would certainly invalidate the results of any such survey.11 To achieve meaningful data from an epidemiologic survey regarding HCV transmission, all recognized risk factors for HCV transmission (e.g., tattoos, snorting nasal cocaine, birth in underdeveloped countries, hemodialysis, sharing of household items, being in prison, and sexual factors) must be considered.12–14 The current study sought to identify sexual and other risk factors that distinguish between HIV-monoinfected and HCV/HIV-coinfected individuals.
This was a cross-sectional study conducted from January 28, 2005, to May 13, 2005. Patients were selected by convenience sampling from 2 urban clinics catering specifically to patients who are HIV-infected and those with liver disease in Phoenix, Arizona. A trained physician researcher attended the HIV and liver disease clinics 3 times a week throughout the study period, approached potential subjects in the waiting room at each location, and told prospective subjects the study was designed to identify risk factors for HCV transmission in an HIV-infected population. Each potential subject was told that their involvement in the study would consist of the completion of a self-administered survey that would take 5 to 10 minutes and that the researchers would have access to their medical records, but their personal information would be kept confidential. A total of 360 patients were approached, and 316 (88%) agreed to participate.
The questionnaires were administered in both English and Spanish depending on the subject's preference and included questions about their demographic characteristics, HIV/ hepatitis status, and a survey of potential sexual and nonsexual risk factors for HCV transmission. The specific information obtained regarding HCV risk factors included: birth outside the United States, needlestick injury sustained at work, use of intravenous or inhaled drugs, sharing of razors or toothbrushes, body piercing, exposure to blood or blood products, hemodialysis, frequency of sexual intercourse, sexual preference, number of sexual partners, involvement with unprotected anal intercourse, sex with an IVDU, the presence of commercial tattoos, history of any sexually transmitted disease (herpes, syphilis, genital warts, and gonorrhea), and being in prison. A chart review was conducted to abstract respondents' laboratory data, including HCV-AB, HCV-RNA, HCV genotype, and HIV-RNA. Clinical data were then linked to the survey data. The hospital Institutional Review Board at the Maricopa Medical Center approved the study.
Demographic and risk factors associated with coinfection status at an α level of 0.1 using univariate χ2 analyses were entered into a multivariate Cox regression model. Cox regression was used instead of logistic regression to reduce the spurious inflation of odds ratios associated with analyzing a nonrare outcome. When a Cox regression method is used and a constant risk factor is assigned to everyone in the sample, the odds ratio equals the prevalence ratio in a cross-sectional study.15,16 Odds ratios with P values of 0.05 or less were considered statistically significant. SPSS statistical software, version 10.1 (SPSS, Inc., Chicago, IL) was used for analysis.
Among the 316 patients who completed the survey, 74 were HCV-infected but not HIV-infected. Because the purpose of this analysis was to examine risk factors for HCV transmission in patients with HIV, these 74 subjects were excluded from the analysis, leaving a sample of 242 HIV-positive patients for analysis. Using the conservative assumption of 50% prevalence of risk factors in the HIV group, this sample size provided power to detect differences of 25% between groups with 80% power and 95% confidence using 2-tailed tests. Among the 242 patients, 168 (69.4%) were HIV- monoinfected and 74 were coinfected (30.6%) with HIV/HCV. Over half (52.5%) of participants were white, 13.2% were black, 11.2% were Hispanic, 4.5% were Native American, and 1.7% were Asian. Just over 15% listed their race as “other” and 1.2% were missing data on race. Fifty-three subjects were born outside the United States; 33 were born in areas or countries close to the United States: one in Canada, one in Puerto Rico, and 31 in Mexico. The average age of the study subjects was 42.3 (± 9.3 years; range, 19–66 years). The HIV-monoinfected subjects tended to be slightly younger than the HIV/HCV-coinfected patients (41.4 vs. 44.4, P = 0.02).
In univariate analyses, coinfected patients reported having a greater prevalence (0.1 α level) of the following risk factors: IVDU, snorting drugs, sharing razors or toothbrushes, time in prison, the presence of a tattoo, sex for money or drugs, and sex with an IVDU (Table 1). The prevalence of MSM (among males only) was greater in the HIV-monoinfected subjects than those who were HIV/HCV-coinfected. Other sexual risk factors, including a history of having a sexually transmitted disease and 11 or more lifetime sexual partners, were common in both groups. Despite a higher prevalence of MSM in the HIV-monoinfected group, more than 70% of respondents in both groups reported practicing unprotected anal intercourse. The prevalence of having had a blood transfusion was similar in both groups. When the risk factors identified in the univariate analysis were included in a multivariate Cox regression model, only IVDU remained as a significant risk factor for HCV infection (Table 2). HIV-positive patients with a history of intravenous drug use were 4.5 times as likely to be coinfected with HCV than those without a history of IVDU.
Because those engaging in MSM comprise a unique patient subpopulation, a subanalysis was accomplished using the data of these patients (Table 3). MSM patients who were coinfected had a greater prevalence of the following risk factors: IVDU, snorting drugs, sharing razors/toothbrushes, tattoos, sex for money or drugs, sex with an IVDU, and having 11 or more sexual partners. Conversely, a history of a sexually transmitted disease and 11 or greater sex partners were more prevalent among HIV-monoinfected patients (Table 3). Because of a smaller sample size for MSM, a multivariate analysis has not been included.
Among the 9,962 individuals infected with HIV in Arizona, 1,169 are coinfected with HCV (11.7%) compared with 78 of 242 (32.2%) HCV subjects in this sample. The higher number of HCV-positive subjects in this sample is the result of patient recruitment from the liver clinic where patients with HCV were specifically referred. A high rate of IVDU was identified among HIV/HCV-coinfected patients reported in these data (63.5%) and is consistent with the 66% rate of IVDU reported for the Arizona HIV-coinfected population.17 Approximately 95% of MSM in both HCV-positive and -negative groups reported ever having unprotected anal intercourse (UAI). It is unclear whether UAI occurred with regular or casual partners or with the partners of the same serostatus. Nonetheless, UAI is common in HIV-positive patients, and a recent study reported more than 50% MSM as having greater than 95 lifetime partners with 87% of subjects having UAI with their last seroconcordant partner.18 In addition, even among HIV-negative MSM followed up in the Omega cohort study, 62.5% reported having UAI.10
This study examines HCV risk factors in only HIV-infected patients. A higher prevalence of HCV has been described in patients with HIV compared with the general population.19 In a comparative study of HIV-positive and HIV-negative subjects, a significantly higher percentage of HIV-positive patients who did not report drug abuse or blood transfusion were found to be infected with HCV, providing putative evidence for sexual transmission of HCV. Unfortunately, several confounding factors such as sharing of household items and syringe use were not controlled for in this study.6 Although a 7.7% HCV prevalence has been reported in non-IVDU, HIV-positive patients,20 a prospective 10-year follow up of noninfected partners of HCV/HIV-coinfected patients with an estimated 5,800 having unprotected vaginal or anal intercourse showed no seroconversion to HCV.21 In addition, among heterosexual HCV/HIV-discordant couples, no HCV seroconversion was reported.22 Finally, a recent study by Minola et al did not find sexual transmission as an independent risk factor for HCV transmission among the family members of HCV cases, because many of them were using intravenously drugs also.23
The finding that there is not an increased prevalence of sexual risk factors in coinfected patients compared with HIV-infected patients is new. In fact, several, non-IVDU-related sexual risk factors (e.g., unprotected anal intercourse, sexually transmitted diseases, number of sex partners) were equally prevalent in the HIV- and HIV/HCV-coinfected groups. Sexual risk factors related to IVDU, however (e.g., sex for money or drugs and sex with an IVDU), were found to be more prevalent in the coinfected group. Taken together, these findings suggest that IVDU is the overarching risk factor distinguishing HIV-monoinfected subjects from the HIV/HCV-coinfected individuals.
Despite these findings, the reported presence of HCV-RNA in genital secretions, albeit in low titers (100 copies/mL), makes sexual transmission of HCV plausible. Traumatic intercourse may contribute to a loss of mucosal defense barriers and may facilitate sexual transmission.24,25 In one case report, sexual transmission of HCV was suggested because the onset of acute hepatitis correlated with the removal of an intrauterine device.26 Based on the Centers for Disease Control and Prevention data, up to two thirds of acute HCV-infected patients report a sexual encounter with another anti-HCV-positive individual as their only risk factor for HCV transmission, although many other potential risk factors were not included in this analysis.27
An important limitation of this study is the sample size. A larger sample would have provided greater power to detect differences between HIV-monoinfected and HIV/HCV-coinfected patients, thus providing more certainty about the role of sexual risk factors in the transmission of HCV. For example, the minimum detectable odds ratios for sexual risk factors significant in univariate analysis (sex for money or drugs and sex with an IVDU) were 2.8 and 2.3, respectively. Thus, the odds ratios of 1.37 and 1.34 reported for these risk factors may have been statistically significant in multivariate analysis with a larger sample size. Other limitations include collection of information from a convenience sample and self-reported information. Additionally, the cross-sectional nature of the study precludes one from determining the actual mode of HCV transmission. Finally, sexual transmission of HCV is extremely infrequent and the number of patients recruited in the present analysis is not enough to refute the possibility of sexual transmission. Nonetheless, this study has controlled for important confounders that can potentially affect the outcome variable and documents that in a high-risk population of individuals with HIV, sexual risk factors do not predict HCV infection. The only identifiable risk factor in this unique population is a history of IVDU.
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