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1.  Association Of Hepatitis C With Markers Of Hemostasis In HIV-Infected and Uninfected Women in the Women’s Interagency HIV Study (WIHS) 
Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. HIV infection and treatment are associated with hypercoaguability; thrombosis in HCV is under-investigated. Proposed markers of hemostasis in HIV include higher D-dimer, Factor VIII% and Plasminogen Activator Inhibitor-1 (PAI-1Ag), and lower total Protein S% (TPS), but have not been examined in HCV. We assessed the independent association of HCV with these four measures of hemostasis in a multicenter, prospective study of HIV: the Women’s Interagency HIV Study (WIHS).
We randomly selected 450 HCV-infected (anti-HCV+ with detectable plasma HCV RNA) and 450 HCV-uninfected (anti-HCV−) women. HCV was the main exposure of interest in regression models.
443 HCV+ and 425 HCV− women were included. HCV+ women had higher Factor VIII% (124.4% ±3.9 vs. 101.8% ±3.7, p <0.001) and lower TPS (75.7% ±1.1 vs. 84.3% ±1.1, <0.001) than HCV−, independent of HIV infection and viral load; there was little difference in PAI-1Ag or log10 D-dimer. After adjustment for confounders, these inferences remained. HIV infection was independently associated with higher Factor VIII% and log10 D-dimer, and lower TPS.
HCV was independently associated with higher Factor VIII% and lower TPS consistent with hypercoaguability. Higher Factor VIII % and D-dimer and lower total Protein S % were also strongly associated with HIV infection and levels of HIV viremia, independent of HCV infection. Further investigation is needed to determine if there is increased thrombotic risk from HCV. Studies examining hemostasis markers in HIV infection must also assess the contribution of HCV infection.
doi:10.1097/QAI.0b013e31827fdd61
PMCID: PMC3652915  PMID: 23221984
2.  Interleukin 10 Responses Are Associated With Sustained CD4 T-Cell Counts in Treated HIV Infection 
The Journal of Infectious Diseases  2012;206(5):780-789.
Background.Inflammation persists in treated human immunodeficiency virus (HIV) infection and may contribute to an increased risk for non–AIDS-related pathologies. We investigated the correlation of cytokine responses with changes in CD4 T-cell levels and coinfection with hepatitis C virus (HCV) during highly active antiretroviral treatment (HAART).
Methods.A total of 383 participants in the Women's Interagency HIV Study (212 with HIV monoinfection, 56 with HCV monoinfection, and 115 with HIV/HCV coinfection) were studied. HIV-infected women had <1000 HIV RNA copies/mL, 99.7% had >200 CD4 T cells/μL; 98% were receiving HAART at baseline. Changes in CD4 T-cell count between baseline and 2–4 years later were calculated. Peripheral blood mononuclear cells (PBMCs) obtained at baseline were used to measure interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 12 (IL-12), and tumor necrosis factor α (TNF-α) responses to Toll-like receptor (TLR) 3 and TLR4 stimulation.
Results.Undetectable HIV RNA (<80 copies/mL) at baseline and secretion of IL-10 by PBMCs were positively associated with gains in CD4 T-cell counts at follow-up. Inflammatory cytokines (IL-1β, IL-6, IL-12, and TNF-α) were also produced in TLR-stimulated cultures, but only IL-10 was significantly associated with sustained increases in CD4 T-cell levels. This association was significant only in women with HIV monoinfection, indicating that HCV coinfection is an important factor limiting gains in CD4 T-cell counts, possibly by contributing to unbalanced persistent inflammation.
Conclusions.Secreted IL-10 from PBMCs may balance the inflammatory environment of HIV, resulting in CD4 T-cell stability.
doi:10.1093/infdis/jis380
PMCID: PMC3491747  PMID: 22693231
4.  Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis 
AIDS (London, England)  2012;26(5):599-607.
Objective
Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART.
Methods
HCV/HIV-co-infected women on antiretroviral therapy enrolled in Women’s Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed.
Results
Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death.
Conclusion
Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.
doi:10.1097/QAD.0b013e32834fa121
PMCID: PMC3698040  PMID: 22156972
fibrosis markers; hepatitis C virus; HIV; longitudinal study; mortality
5.  Hepatitis C Viremia Is Associated with Cytomegalovirus IgG Antibody Levels in HIV-Infected Women 
PLoS ONE  2013;8(4):e61973.
Background
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.
Methods
Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.
Results
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (Pinteraction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.
Conclusions
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.
doi:10.1371/journal.pone.0061973
PMCID: PMC3629158  PMID: 23613990
6.  The insulin-like growth factor axis and risk of liver disease in hepatitis C virus/HIV-co-infected women 
AIDS (London, England)  2008;22(4):527-531.
Objective
Insulin-like growth factor (IGF) I stimulates the proliferation of hepatic stellate cells (HSC), the primary source of extracellular matrix accumulation in liver fibrosis. In contrast, insulin-like growth factor binding protein (IGFBP) 3, the most abundant IGFBP in circulation, negatively modulates HSC mitogenesis. To investigate the role of the IGF axis in hepatitis C virus (HCV)-related liver disease among high-risk patients, we prospectively evaluated HCV-viremic/HIV-positive women.
Design
A cohort investigation.
Methods
Total IGF-I and IGFBP-3 were measured in baseline serum specimens obtained from 472 HCV-viremic/HIV-positive subjects enrolled in the Women's Inter-agency HIV Study, a large multi-institutional cohort. The aspartate aminotransferase to platelet ratio index (APRI), a marker of liver fibrosis, was assessed annually.
Results
Normal APRI levels (< 1.0) at baseline were detected in 374 of the 472 HCV-viremic/HIV-positive subjects tested, of whom 302 had complete liver function test data and were studied. IGF-I was positively associated [adjusted odds ratio comparing the highest and lowest quartiles (AORq4–q1), 5.83; 95% confidence interval (CI) 1.17–29.1; Ptrend = 0.03], and IGFBP-3 was inversely associated (AORq4–q1, 0.13; 95% CI 0.02–0.76; Ptrend = 0.04), with subsequent (incident) detection of an elevated APRI level(> 1.5), after adjustment for the CD4 T-cell count, alcohol consumption, and other risk factors.
Conclusion
High IGF-I may be associated with increased risk and high IGFBP-3 with reduced risk of liver disease among HCV-viremic/HIV-positive women.
doi:10.1097/QAD.0b013e3282f22cdf
PMCID: PMC3507535  PMID: 18301066
aspartate aminotransferase to platelet ratio index; APRI; hepatitis C virus (HCV); HIV; IGFBP-3; IGF; liver disease
7.  Factors associated with hepatitis C viremia in a large cohort of HIV-infected and - uninfected women 
Background
Coinfection with hepatitis C virus (HCV) is common among HIV-infected women.
Objective
To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women.
Study design
We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 882 HIV-infected and 167 HIV-uninfected HCV-seropositive women at entry into the Women's Interagency HIV Study.
Results
Plasma HCV RNA was detected in 852 (81%) of these 1,049 women (range: 1.2–7.8 log10 copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P =0.0004), have reported smoking (P =0.01), or to be Black (P =0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia.
Conclusions
Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women.
doi:10.1016/j.jcv.2007.08.021
PMCID: PMC3493623  PMID: 18243785
Hepatitis C; Hepatitis C RNA levels; Hepatitis C viremia; HIV/hepatitis C virus coinfection
8.  Contexts of risk and networks of protection: NYC West Indian immigrants’ perceptions of migration and vulnerability to sexually transmitted diseases 
Culture, health & sexuality  2011;13(5):513-528.
To generate insights into how migration shapes sexual risk and protection, we interviewed 36 female and 20 male West Indian (WI) immigrants attending a public sexually transmitted disease (STD) clinic in Brooklyn, NY between 2004 and 2005. Migration theory suggests that shifts in sexual partnership patterns, bi-directional travel, and changes in sexual norms may alter risk. We found evidence of sexual mixing across ethnic groups: a large proportion of participants’ partners were not born in the WIs, despite what is expected among first generation immigrants. Recent travel “home,” another potential source of risk, was uncommon. In open-ended interviews, two themes around sexual and social networks emerged. First, immigrants believed that access to wider, more anonymous sexual networks in NYC and the weakening of social controls that limit multiple partnerships (especially for women) promoted greater risk. Second, immigrants experienced greater opportunities for protection in NYC, both through exposure to safer sex messages and availability of condoms. Reported changes in their own condom use, however, were not attributed to migration. WI immigrants’ risk in NYC may be driven by access to wider sexual networks but failure to alter reliance on “networks of knowledge” for protection.
doi:10.1080/13691058.2011.562304
PMCID: PMC3407273  PMID: 21452091
Caribbean; West Indian; migration; sexual health; sexual networks; HIV/STD
9.  Isolated Hepatitis B Core Antibody Is Associated with HIV and Ongoing but Not Resolved Hepatitis C Virus Infection in a Cohort of US Women 
The Journal of infectious diseases  2007;195(10):1437-1442.
To characterize predictors of isolated hepatitis B core antibody (anti-HBc) among human immunodeficiency virus (HIV)–infected and HIV-uninfected women, we compared 702 women with anti-HBc and hepatitis B surface antibody (anti-HBs) with 490 women with isolated anti-HBc (1.8% of whom had detectable hepatitis B virus [HBV] DNA). Factors independently associated with isolated anti-HBc without viremia were detectable hepatitis C virus (HCV) RNA, HIV positivity, history of injection drug use, >10 lifetime sex partners, and HIV RNA level >100,000 copies/mL. Anti-HBs levels were lower among anti-HCV–positive women. Isolated anti-HBc was rarely explained by occult HBV in this cohort but may be explained by the influence of viral coinfections on anti-HBs level or durability.
doi:10.1086/515578
PMCID: PMC3133731  PMID: 17436223
10.  Association between Syphilis, Antibodies to Herpes Simplex Virus Type 2, and Recreational Drug Use and Hepatitis B Virus Infection in the Women’s Interagency HIV Study 
Background
Liver disease is a leading cause of death in human immunodeficiency virus (HIV)–infected women; however, risk factors for hepatitis B virus (HBV) infection in this population have not been well studied.
Methods
We describe the seroprevalence and predictors of HBV infection in a cross-sectional analysis of 2132 women with and at risk for HIV infection enrolled in the Women’s Interagency HIV Study during the periods 1994–95 and 2001–02. Any test result positive for antibody to hepatitis B core antigen defined infection; those women with serological evidence of vaccine immunity were excluded from analysis. Women were stratified into those with a history of injection drug use (IDU), those with a history of noninjection drug use (non-IDU), and those with no history of illicit drug use.
Results
Of 1606 HIV-infected and 526 HIV-uninfected women, 7% and 12%, respectively, appeared to be vaccine immune. After exclusion of these women, 43% of 1500 HIV-infected and 22% of 461 HIV-uninfected women had HBV infection. HBV infection prevalence differed among the IDU, non-IDU, and no illicit drug use groups (76%, 30%, and 17%, respectively; P < .0001). HBV infection was strongly associated with herpes simplex virus 2 (HSV-2) seropositivity in the IDU group (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6–5.4) and with a history of syphilis in the non-IDU group (OR, 2.7; 95% CI, 1.4–5.0).
Discussion
We found a high prevalence of HBV infection in our cohort of women with and at risk for HIV infection. HSV-2 seropositivity and a history of syphilis appeared to be important correlates of HBV infection. Sexual transmission of HBV, particularly in those with a history of genital ulcer disease, should be a major focus of education in all high-risk groups.
doi:10.1086/424879
PMCID: PMC3118996  PMID: 15494914
11.  The Effects of Opiate Use and Hepatitis C Virus Infection on Risk of Diabetes Mellitus in the Women’s Interagency HIV Study 
Background
Opiate use is common in HIV- and hepatitis C virus (HCV)-infected individuals, however its contribution to the risk of diabetes mellitus is not well understood.
Methods
Prospective study of 1,713 HIV-infected and 652 uninfected participants from the Women’s Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose ≥126 mg/dl, or self-report of diabetes medication use or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection.
Results
Current opiate users had a higher prevalence of diabetes (15%) than non-users (10%, p=.03), as well as a higher risk of incident diabetes (adjusted relative hazard [RHadj] 1.58, 95% CI 1.01, 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status and diabetes risk factors including age, race/ethnicity, family history of diabetes and body mass index. HCV infection was also an independent risk factor for diabetes (RHadj 1.61, 95% CI 1.02, 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases/100 person-years).
Conclusions
Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users, and those infected with HCV.
doi:10.1097/QAI.0b013e3181d0c911
PMCID: PMC3069645  PMID: 20190642
opiate use; diabetes mellitus; fasting glucose; Hepatitis C virus; HIV; women
12.  Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus 
The Journal of infectious diseases  2010;201(6):823-834.
Background
Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression.
Methods
Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated.
Results
HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8+CD38+DR+ T cells (hazard ratio, 2.94 [95% confidence interval, 1.50–5.77]; P =.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80–4.35]; P =.16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8+CD38−DR+, CD4+CD38−DR−, and CD8+CD38−DR− T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women.
Conclusion
HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.
doi:10.1086/650997
PMCID: PMC3105602  PMID: 20151840
13.  Hepatitis C Seropositivity and Kidney Function Decline Among Women With HIV: Data From the Women's Interagency HIV Study 
Background
How co-infection with hepatitis C virus (HCV) impacts on the trajectory of kidney function among HIV-infected patients is unclear. This study examined the effect of HCV on kidney function over time among women infected with HIV.
Study Design
Retrospective observational cohort
Setting and Participants
Study sample included participants from the Women's Interagency HIV Study who were HIV-infected and had received HCV antibody testing and serum creatinine measurement at baseline.
Predictor
HCV seropositivity
Outcomes and Measurement
Estimated glomerular filtration rate (eGFR) calculated from semi-annual serum creatinine measurements using the 4-variable Modification of Diet in Renal Diseases (MDRD) Study equation. Linear mixed models were used to evaluate the independent effect of being HCV seropositive on eGFR over time, adjusting for demographic factors, co-morbid conditions, illicit drug use, measures of HIV disease status, use of medications, and interactions with baseline low eGFR (<60 mL/min/1.73m2).
Results
Of the 2,684 HIV-infected women, 952 (35%) were found to be HCV seropositive. For 180 women with CKD at baseline (eGFR <60 mL/min/1.73m2), being HCV seropositive was independently associated with a fully-adjusted net decline in eGFR of about 5% per year (95% CI: 3.2 to 7.2%), relative to women who were seronegative. In contrast, HCV was not independently associated with decline in eGFR among women without low eGFR at baseline (p<0.001 for interaction).
Limitations
The MDRD Study equation has not been validated as a measure of GFR among persons with HIV or HCV. Proteinuria was not included in the study analysis. Because the study is observational, the effects of residual confounding cannot be excluded.
Conclusions
Among HIV-infected women with CKD, co-infection with HCV is associated with a modest, but statistically significant decline in eGFR over time. More careful monitoring of kidney function may be warranted for HIV-infected patients with CKD who are also co-infected with HCV.
doi:10.1053/j.ajkd.2009.02.009
PMCID: PMC2997705  PMID: 19394735
hepatitis C virus; HIV; kidney diseases; women
14.  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  2009;23(11):915-923.
Abstract
Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women's Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different (p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.
doi:10.1089/apc.2009.0111
PMCID: PMC2823487  PMID: 19877800
15.  Trends in Mortality and Causes of Death among Women with HIV in the US: A Ten-year Study 
Background
To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10 year period among participants in the Women’s Interagency HIV Study (WIHS), a representative US cohort.
Methods
Deaths were ascertained by National Death Index-Plus match and causes of death determined by death certificate.
Results
From 1995 through 2004, 710 of 2792 HIV-infected participants died. During this interval the standardized mortality ratio (SMR) fell from a high of 24.7 in 1996 to a plateau with a mean of 10.3 from 2001–2004. Over the decade, deaths from non-AIDs causes increased and accounted for the majority of deaths by 2001–2004. The most common non-AIDS causes of death were trauma or overdose, liver disease, cardiovascular disease and malignancy. Independent predictors of mortality besides HIV-associated variables were depressive symptoms, and active hepatitis B or C. Women who were overweight or obese were significantly less likely to die of AIDS than women of normal weight.
Conclusion
In the WIHS, the death rate has plateaued in recent years. While HIV-associated factors predicted AIDS and non-AIDS deaths, other treatable conditions predicted mortality. Further gains in reducing mortality among HIV-infected women may require broader access to therapies for depression, viral hepatitis and HIV itself.
doi:10.1097/QAI.0b013e3181acb4e5
PMCID: PMC2769934  PMID: 19487953
HIV; mortality; women; viral hepatitis; non-AIDs mortality
16.  Long-Term Serologic Follow-Up of Isolated Hepatitis B Core Antibody in HIV-Infected and HIV-Uninfected Women 
Background
Isolated antibody to hepatitis B core antigen (anti-HBc) is a common serologic finding in persons infected with human immunodeficiency virus (HIV), but the outcome and clinical significance are uncertain.
Methods
We performed repeated hepatitis B virus (HBV) serologic tests on women who participated in the Women’s Interagency HIV Study and who had isolated anti-HBc at study entry.
Results
Repeated serologic tests were performed for 322 women (282 HIV-infected and 40 HIV-uninfected) at a median of 7.5 years after study entry. Seventy-one percent of women retained isolated anti-HBc serologic status, 20% acquired antibody to hepatitis B surface antigen (anti-HBs), and 2% acquired hepatitis B surface antigen (HBsAg). In unadjusted analysis, increasing age, injection drug use, and hepatitis C viremia were negatively associated with acquisition of anti-HBs. For HIV-infected women, predictors of acquisition of anti-HBs were an increase in CD4 cell count and the use of highly active antiretroviral therapy (HAART). Receipt of drugs with activity against HBV and self-reported HBV vaccination did not predict anti-HBs acquisition. In the multivariable regression model, HAART use remained a significant predictor of anti-HBs acquisition, whereas women with hepatitis C viremia were more likely to retain isolated anti-HBc serologic status.
Conclusions
Isolated anti-HBc status remained stable over time for the majority of women, especially women with chronic hepatitis C virus infection. Development of anti-HBs was predicted by HAART use and an increase in CD4 cell count. We conclude that a proportion of HIV-infected women with isolated anti-HBc have prior natural HBV infection with anti-HBs that is at an undetectable level because of immune dysfunction. Isolated anti-HBc in the presence of chronic hepatitis C virus infection may be attributable to a different phenomenon, such as dysfunctional antibody production.
doi:10.1086/599610
PMCID: PMC2743413  PMID: 19480573
17.  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  2009;23(11):915-923.
Although the primary mode of hepatitis C virus (HCV) transmission is exposure to blood products or injection drug use (IDU), studies have found varying independent risk factors for HCV infection among persons with no history of IDU or exposure to blood products. For HIV-infected women, sexual transmission may be another potential source of HCV infection. HIV-infected and HIV-negative women at risk for HIV enrolled in the Women’s Interagency HIV Study (WIHS) during October 1994 to November 1995 and again between October 2001 and November 2002 were studied. Clinical and demographic factors associated with HCV seroprevalence were assessed in multivariate logistic regression models controlling for history of blood transfusion and IDU. Among 3636 women with HCV results, 31.5% were HCV antibody positive (HCV+) including 13.5% with no reported history of IDU or blood transfusions. Multivariate logistic regression analyses stratified on IDU showed that among women with no history of IDU, sex with an IDU male was independently associated with HCV positivity (odds ratio [OR] = 2.8, 95% confidence [CI] = 2.1, 3.8, p < 0.0001) after controlling for blood transfusion, age, HIV infection, unemployment, birth in the United States, history of hepatitis B infection, and current smoking status. Further stratification on HIV status showed that the association was significant only for the HIV+ (OR = 1.9, 95% CI = 1.3, 2.7, p = 0.0007) compared to the HIV− women (OR = 1.1, 95% CI = 0.4, 2.7) although these odds ratios were not significantly different ( p = 0.25). For HIV-positive women with no reported history of IDU, sex with an IDU male was independently associated with HCV suggesting that sexual transmission may be an important mode of HCV transmission for these high-risk women.
doi:10.1089/apc.2009.0111
PMCID: PMC2823487  PMID: 19877800
18.  Awareness of Hepatitis C Infection Among Women With and At Risk for HIV 
Journal of General Internal Medicine  2007;22(12):1689-1694.
BACKGROUND
Treatment guidelines recommend all HIV/HCV-co-infected persons be considered for hepatitis C virus (HCV) treatment, yet obstacles to testing and accessing treatment for HCV continue for women.
OBJECTIVE
To assess awareness of HCV, and describe diagnostic referrals and HCV treatment among women in the Women’s Interagency HIV Study (WIHS).
DESIGN
Prospective epidemiologic cohort.
PARTICIPANTS
Of 3,768 HIV-infected and uninfected women in WIHS, 1,166 (31%) were HCV antibody positive.
MEASUREMENTS AND MAIN RESULTS
Awareness of HCV infection and probability of referrals for diagnostic evaluations and treatment using logistic regression. Follow-up HCV information was available for 681 (390 died, 15 withdrew, 80 missed visit) in 2004. Of these 681, 522 (76.7%) reported knowing their HCV diagnosis. Of these, 247 of 522 (47.3%) stated their providers recommended a liver biopsy, whereas 139 of 247 or 56.3% reported having a liver biopsy. A total of 170 of 522 (32.6%) reported being offered treatment and 74.1% (n = 126 of 170) reported receiving HCV treatment. In multivariate regression analyses, African-American race, Hispanic/Latina ethnicity, poverty, and current crack/cocaine/heroin use were negatively associated with treatment referrals, whereas elevated alanine aminotransferase (ALT) was associated with increased likelihood of referral and increased likelihood of treatment.
CONCLUSION
One quarter of women with HCV in this cohort were not aware of their diagnosis. Among those aware of their HCV, 1 in 4 received liver biopsy and treatment for HCV. Both provider and patient education interventions regarding HCV testing and HCV treatment options and guidelines are needed to enhance HCV awareness and participation in HCV evaluation and treatment.
doi:10.1007/s11606-007-0395-x
PMCID: PMC2219830  PMID: 17924170
women; hepatitis C; HIV; race; drug use; therapy
19.  Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression 
Background
Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates.
Methods
We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use.
Results
Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before.
Conclusion
In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.
doi:10.1186/1471-2334-7-145
PMCID: PMC2238758  PMID: 18070362
20.  Predictors of Partner Notification for C. trachomatis and N. gonorrhoeae: An Examination of Social Cognitive and Psychological Factors 
Efforts to control chlamydial and gonococcal infections include notifying eligible sexual partners of possible infection, primarily by asking the diagnosed patient to notify their partners. This approach, known as patient referral, is widely used but poorly understood. The current study examined psychosocial and cognitive factors associated with patient referral among an urban, minority sample of 168 participants recently diagnosed with Chlamydia trachomatis or Neisseria gonorrhoeae. At a follow-up interview 1-month from diagnosis, participants were more likely to have notified all eligible partners if they had greater intention to notify at baseline (OR = 3.72; 95% CI = 1.34, 10.30) and if they had only one partner at baseline (OR = 4.08; 95% CI = 1.61, 10.31). There were also gender differences as well as differences based on type of partner (i.e., regular, casual, one-time). The implications of these findings for the design of programs to promote patient referral for sexually transmitted infections are discussed.
doi:10.1007/s11524-006-9087-9
PMCID: PMC3261298  PMID: 16817010
Partner notification; Patient referral; STI

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