Hepatitis C Seroprevalence Among HIV-Infected Childbearing Women in New York State in 2006

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1 DOI /s Hepatitis C Seroprevalence Among HIV-Infected Childbearing Women in New York State in 2006 L. Ghazaryan 1 L. Smith 2 M. Parker 3 C. Flanigan 4 W. Pulver 2 T. Sullivan 5 A. Carrascal 6 Springer Science+Business Media New York 2015 Abstract Objective To identify factors associated with maternal hepatitis C virus (HCV) seroprevalence and transmission of HCV as identified by qualitative HCV ribonucleic acid (RNA) in the infants of human immunodeficiency virus (HIV) infected women delivering in New York State (NYS) in Study Design In this retrospective cohort study of HIV-exposed infants born in NYS, leftover infant plasma from HIV diagnostic testing was deidentified and tested for HCV. If HCV antibodies were detected, a second specimen collected when the infant was [2 months old was tested for HCV qualitative RNA. Multivariate logistic regression was used to identify factors associated with HCV seropositivity. Results In a final sample of 553 live birth events with perinatal HIV exposure, 21 (3.8 %) of tested infant specimens had HCV antibodies indicative of maternal HCV seropositivity. Maternal age at delivery of [35 years, Hispanic ethnicity, white race and injection drug use (IDU) were significantly associated with HCV seropositivity in multivariate analysis. No cases of HCV vertical transmission were identified among HCV exposed infant specimens. Conclusions This statewide population-based study of HIV-infected childbearing women shows HCV seroprevalence of 3.8 %. Maternal age of [35 years and IDU are the strongest predictors of HCV seropositivity. Although no viral transmission was documented, more comprehensive longitudinal testing would be required to conclude that HCV transmission did not occur. Keywords Hepatitis C HIV Pregnant New York State Seroprevalence & L. Ghazaryan lusine.ghazaryan@health.ny.gov L. Smith lou.smith@health.ny.gov M. Parker monica.parker@health.ny.gov C. Flanigan colleen.flanigan@health.ny.gov W. Pulver wendy.pulver@health.ny.gov T. Sullivan timothy.sullivan@health.ny.gov A. Carrascal alvaro.carrascal@cancer.org Division of Epidemiology, Evaluation and Research, New York State Department of Health, Corning Tower, ESP, Albany, NY 12237, USA Bloodborne Viruses Laboratory, Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA Viral Hepatitis Section, AIDS Institute, New York State Department of Health, ESP, Corning Tower Room 429, Albany, NY 12237, USA Wadsworth Center, New York State Department of Health, 120 New Scotland Avenue, Albany, NY 12208, USA Cancer Control, American Cancer Society, Eastern Division, One Penny Lane, Latham, NY 12110, USA 1 Surveillance and Special Projects Unit, Bureau of STD Prevention and Epidemiology, AIDS Institute, New York State Department of Health, ESP, Corning Tower, Albany, NY 12237, USA

2 Abbreviations HCV Hepatitis C virus HIV Human immunodeficiency virus IDU Injection drug use NHANES National Health and Nutrition Examination Survey NYS New York State NYSDOH New York State Department of Health RNA Ribonucleic acid Significance This statewide population-based study of HIV-infected childbearing women shows HCV seroprevalence of 3.8 %. The study results help in better understanding of the overall epidemiology of HCV and reinforce the current HCV screening recommendations among pregnant women infected with HIV. The identified seroprevalence of HCV may raise awareness among health care providers and ensure appropriate HCV screening and early identification of HCV among HIV infected women of childbearing age (15 45 years old). Background Hepatitis C virus (HCV) infection is a serious public health problem. Centers for Disease Control and Prevention (CDC) estimates that approximately 2.7 million Americans are chronically infected with HCV and most are unaware of their infection [1]. In the National Health and Nutrition Examination Survey (NHANES), 1.3 % of the US population was anti-hcv positive and 1.0 % was HCV ribonucleic acid (RNA) positive [1]. Injection drug users (IDU) have the highest prevalence of HCV accounting for 90 % of all new infections worldwide [2]. If left untreated, HCV can lead to serious liver damage including cirrhosis, liver failure and hepatocellular carcinoma [3]. Recent advances in HCV treatment have rendered HCV a curable condition with [90 % of treated persons cured of their HCV disease [4]. However, the safety and efficacy of treating pregnant women to prevent transmission to the fetus have not yet been established. Therefore, treatment is not recommended for pregnant women and cannot be used prophylactically in newborns. The prevalence of HCV infection among women of childbearing age (15 45 years old) in the US is 1 % [5]. The prevalence of HCV in pregnant women is estimated to be % in the US and European countries [6]. The prevalence of HCV infection in pregnant women increases when the mother has risk factors associated with HCV such as IDU. Among pregnant women with a history of IDU, the HCV prevalence is estimated to be % [7]. The prevalence of HCV among HIV-infected pregnant women has been reported to be % [8]. The rate of mother-to-child transmission (MTCT) is 4 7 % per pregnancy in women with HCV [9]. The rate of MTCT is much higher among HIV/HCV coinfected mothers ranging from 8.7 to 19 % [10, 11]. This study was conducted on a complete state-wide cohort of HIV-infected women of childbearing age. The study assessed maternal HCV seroprevalence and qualitative HCV RNA in the infants of HIV-infected women delivering in New York State (NYS) in Methods For this retrospective cohort study, multiple data sources were used to identify HIV-infected deliveries, routine maternal and infant medical records, and HCV screening and diagnostic testing results of HIV-exposed infants. They included universal newborn metabolic screening of heelstick specimens for HIV antibodies and medical record review of the identified HIV-exposed infants and the prenatal care charts of their mothers. Additional data were obtained from the New York State Department of Health s (NYSDOH) Pediatric HIV Testing Service, which offers HIV diagnostic testing for all HIV-exposed infants born in NYS. Further details of this process have been described elsewhere [12]. In 2006, the NYSDOH recommended collecting whole blood from HIV-exposed infants at 0 2 days, 2 weeks, 4 6 weeks, 8 10 weeks and weeks of age for diagnostic testing by the Pediatric HIV Testing Service at the NYSDOH Wadsworth Center Laboratory. Residual plasma from infants born to HIV-infected women between January 1 and December 31, 2006 was stored at minus 80 C atthe NYSDOH Wadsworth Center Laboratory. Specimens were linked to variables extracted from routine maternal and infant medical record review via a unique study identification number. After identifiers were removed, the specimens were tested for HCV. The earliest available plasma specimen (newborns age days old) was tested for the presence of HCV antibodies using the Ortho HCV Version 3.0 enzymelinked immunosorbent assay (ELISA) (Ortho Clinical Diagnostics, Inc. Raritan, NJ) according to the manufacturer s instructions. Specimens that produced a non-reactive result on this antibody screening test did not receive any further testing. A signal-to-cutoff ratio [3.8 has been established for this assay as being predictive of a true antibody positive

3 Table 1 Maternal characteristics by hepatitis C virus serostatus Maternal characteristic Total (N = 553) #% HCV seronegative (n = 532) HCV seropositive (n = 21) Race/ethnicity Black Hispanic White Other/unknown Age at delivery (years) \ ? HIV transmission risk Heterosexual IDU Perinatal infection Unknown Residence New York City Rest of New York State Prenatal care Yes No/unknown Number of prenatal care visits \ ? Unknown Length of time of membrane rupture \2 h [2 h Unknown Mode of delivery C-section Vaginal/unknown Timing of HIV diagnosis Before pregnancy During pregnancy At or after delivery CD4 lymphocyte test conducted during pregnancy Yes No Unknown CD4 lymphocyte test conducted closest to delivery \ C Unknown HIV viral load test conducted during pregnancy Yes

4 Table 1 continued Maternal characteristic Total (N = 553) #% HCV seronegative (n = 532) HCV seropositive (n = 21) No Unknown HIV viral RNA load \ , [10, Unknown Diagnosed with hepatitis B during pregnancy Yes No Unknown HCV hepatitis C virus, HIV human immunodeficiency virus, RNA ribonucleic acid Table 2 Infant characteristics by maternal HCV serostatus Infant characteristic Total (N = 553) HCV seronegative (n = 532) HCV seropositive (n = 21) Birthweight (in grams) \ C Gestational age at birth (in weeks) \ C Sex Female Male Age at early specimen collection \ 4 weeks weeks [12 weeks Age at late specimen collection 8 12 weeks [12 weeks No test HCV hepatitis C virus result [13]. Following this recommendation, repeatedly reactive specimens with a signal-to-cutoff ratio [3.8 were considered confirmed for HCV antibodies. Specimens with a signal-to-cut-off ratios \3.8 underwent supplemental testing using the Chiron RIBA HCV 3.0 Strip Immunoblot Assay (Ortho Clinical Diagnostics, Inc. Raritan, NJ) as recommended to distinguish between a true seropositive and a biologic false positive result. Specimens that required supplemental testing and produced an indeterminate result were classified as indeterminate and excluded from further analysis of study results. The presence of HCV antibodies in the infant s plasma was attributed to the placental transfer of maternal HCV antibodies due to either a current or past hepatitis C infection. Among HCV antibody-positive infants, specimens collected when the infants were [2 months old were tested for HCV RNA using the Aptima HCV RNA qualitative assay (Hologic Gen-Probe, Inc., San Diego, CA). For

5 Table 3 Multivariate analysis: adjusted relative risks with 95 % confidence intervals for selected variables predictive of maternal HCV seroprevalence Individual characteristic RR 95 % CI Maternal age at delivery, years (3.2; 27.7) Injection drug use No 1.0 (2.0; 36.1) Yes 8.6 Race and ethnicity Black NH 1.0 (1.6; 13.9) Hispanic 4.6 (0.0; 12.9) Other/unknown 1.1 (1.1; 19.2) White NH 4.8 CI confidence interval, HCV hepatitis C virus, RR relative risk delivery events with multiple newborns, data for one of the infants were retained for analysis. Multivariate analysis was used to identify factors associated with HCV seropositivity using demographic, risk and selected prenatal care and delivery variables significant in bivariate analysis (Chi square and Fisher s exact tests). These variables were maternal age at delivery, race and ethnicity, HIV transmission risk, HIV viral load test during pregnancy as well as infant s birthweight. Multivariate logistic regression using Firth s bias was used to ameliorate small sample size related issues for analytic purposes [14]. Results From 591 live birth events with HIV exposure, 33 (5.6 %) infants had insufficient volume of plasma for testing, 3 (0.5 %) had no data from medical record review and 2 (0.3 %) had indeterminate HCV results, yielding a final cohort of 553 (93.6 %). Overall, 21 (3.8 %) (95 % confidence interval [CI] 2.2, 5.4) of tested infant samples had HCV antibodies indicative of maternal HCV seropositivity. Table 1 presents maternal characteristics, including testing history by hepatitis C serostatus whereas Table 2 shows infant characteristics by maternal HCV serostatus. Maternal age at delivery of [35 years (Relative risk [RR] 8.7; 95 % CI 3.2, 27.7), Hispanic ethnicity (RR 4.6; 95 % CI 1.6, 13.9), white race (RR: 4.8; 95 % CI 1.1, 19.2) and injection drug use (RR 8.6; 95 % CI 2.0, 36.1) were significantly associated with maternal HCV seropositivity in multivariate analysis. Table 3 shows results of multivariate analysis with selected variables which were significant predictors of maternal HCV seroprevalence. No cases of vertical transmission of HCV among HIV/HCV coinfected women were identified among 20 (95.2 %) infant specimens which received HCV RNA testing. Discussion Limited research is available on the coinfection of HCV and HIV among women of childbearing age (15 45 years old). Both HCV and HIV are readily transmitted through injection-drug use, and about one-fourth of all HIV patients are also coinfected with HCV [15, 16]. This unique statewide population-based study of a cohort of HIV-infected childbearing women showed HCV seroprevalence of 3.8 %. During the year of 2006, the perinatal HIV transmission rate in the cohort of 600 (9 cases were out of state residents) HIV exposed birth events followed was 1.7 %. Maternal age of 35 years or older and IDU were the strongest predictors of HCV seropositivity, consistent with the existing body of research [16]. Limitations of our study included the small number of HCV seropositive women, limited maternal risk profile and lack of longer follow up and more comprehensive testing for infants who were identified to be HCV seropositive. To address issues of small sample size we used logistic regression analysis with the Firth s bias reduction, which is a well-accepted approach in analyzing small or sparse samples with highly predictive covariates [14]. Although no viral transmission was documented, more comprehensive longitudinal testing would be required to conclude that HCV transmission did not occur. If the infant became infected during labor or delivery, RNA may not be detectable until several weeks after birth. Therefore, HCV RNA testing was performed on a plasma specimen collected when the infant was 2 months of age or older. However, the fact that HCV RNA was not detected could indicate absence of vertical transmission, infant infection with clearing of HCV, or intermittent/low level viremia not detected by the test. According to national guidelines, all persons with HIV infection should undergo serologic testing for HCV at initial evaluation [17]. Most recently, CDC augmented its previous recommendations for HCV testing [18] to recommend one-time testing without prior ascertainment of HCV risk for persons born during , a population with a disproportionately high prevalence of HCV infection and related disease [19]. Even though routine testing for HCV infection is not recommended for all pregnant women, it is recommended that pregnant women with a known risk factor for HCV infection, such as IDU and HIV infection be offered counseling and testing. Additionally, infants born to HCV-positive mothers should be tested for HCV infection and, if positive, evaluated for the presence of chronic liver disease. The identified seroprevalence of

6 HCV may raise awareness among health care providers and ensure appropriate HCV screening and early identification of HCV among HIV infected women of childbearing age (15 45 years old). Conclusions This unique study assessed HCV seroprevalence in the complete cohort of HIV-infected women who delivered in New York State in Observed HCV seroprevalence was comparable to existing literature [20]. The study results help in better understanding of the overall epidemiology of HCV in the state of New York. Maternal transmission of HCV is the leading cause of pediatric chronic HCV [8]. HCV screening is not recommended universally for all pregnant women. It is routinely recommended for women of childbearing age and pregnant women who present with risk factors associated with HCV transmission and those infected with HIV. The results of this study reinforce the current screening recommendations. In light of the new highly effective HCV treatments, it is essential to identify HCV in women of childbearing age before they become pregnant, so that they may be cured of their HCV infection. This will in turn eliminate the risk of HCV transmission to the newborn and improve their health outcomes. References 1. Denniston, M. M., et al. (2014). Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey Annals of Internal Medicine, 160(5), Hellard, M., Sacks-Davis, R., & Gold, J. (2009). Hepatitis C treatment for injection drug users: A review of the available evidence. Clinical Infectious Diseases, 49(4), Grebely, J., & G.J. Dore, G. J. (2011). What is killing people with hepatitis C virus infection? In Seminars in Liver Diseases. 4. Trooskin, S. B., et al. (2015). Results from a Geographically Focused, Community-Based HCV Screening, Linkage-to-Care and Patient Navigation Program. Journal of General Internal Medicine, 30(7), Alter, M. J., et al. (1999). The prevalence of hepatitis C virus infection in the United States, 1988 through New England Journal of Medicine, 341(8), Arshad, M., El-Kamary, S., & Jhaveri, R. (2011). Hepatitis C virus infection during pregnancy and the newborn period are they opportunities for treatment? Journal of Viral Hepatitis, 18(4), Yeung, L. T., King, S. M., & Roberts, E. A. (2001). Mother-toinfant transmission of hepatitis C virus. Hepatology, 34(2), Dunkelberg, J., et al. (2014). Hepatitis B and C in pregnancy: A review and recommendations for care. Journal of Perinatology,34, Roberts, E. A., & Yeung, L. (2002). Maternal-infant transmission of hepatitis C virus infection. Hepatology, 36(5B), s106 s Thaler, M., et al. (1991). Vertical transmission of hepatitis C virus. The Lancet, 338(8758), Zanetti, A. R., et al. (1995). Mother-to-infant transmission of hepatitis C virus. Lombardy study group on vertical HCV transmission. Lancet, 345(8945), Birkhead, G. S., et al. (2010). Progress in prevention of motherto-child transmission of HIV in New York State: Journal of Public Health Management and Practice, 16(6), CDC. (2013). Testing for HCV infection: An update of guidance for clinicians and laboratorians. Morbidity and Mortality Weekly Report, 62(18), Heinze, G., & Schemper, M. (2002). A solution to the problem of separation in logistic regression. Statistics in Medicine, 21(16), Frederick, T., et al. (2009). Factors associated with prevalent hepatitis C infection among HIV-infected women with no reported history of injection drug use: The Women s Interagency HIV Study (WIHS). AIDS patient care and STDs, 23(11), Hagan, H., Thiede, H., & Des, D. C. (2005). Jarlais, HIV/hepatitis C virus co-infection in drug users: Risk behavior and prevention. AIDS, 19, S199 S AASLD/IDSA HCV Guidance Panel. (2015). Hepatitis C guidance: AASLD-IDSA recommendations fortesting, managing, and treating adults infected with hepatitis C virus. Hepatology, 62(3), Alter, M. J., et al. (1998). Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR. Morbidity and Mortality Weekly Report, 47(1), Smith, B. D., et al. (2012). Recommendations for the identification of chronic hepatitis C virus infection among persons born during MMWR Recommendations and Reports, 61(RR-4), Santiago-Munoz, P., et al. (2005). Prevalence of hepatitis B and C in pregnant women who are infected with human immunodeficiency virus. American Journal of Obstetrics and Gynecology, 193(3 Pt 2),