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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.  Presence of Hepatitis C Virus (HCV) RNA in the Genital Tracts of HCV/HIV-1–Coinfected Women 
The Journal of infectious diseases  2005;192(9):1557-1565.
Background
Hepatitis C virus (HCV)–infected women—in particular, those coinfected with human immunodeficiency virus type 1 (HIV-1)—can transmit infection to their children and sex partners.
Methods
The present study was conducted to analyze the presence of HCV RNA in cervicovaginal lavage (CVL) fluid from 71 women (58 HCV/HIV-1–coinfected women and 13 HCV-infected, HIV-1–uninfected women) enrolled in the Women’s Interagency HIV Study.
Results
HCV RNA was detected (by a commercial polymerase chain reaction assay) in CVL fluid from 18 (29%) of the HIV-1–infected women and from none of the HIV-1–uninfected women (P < .05). Multivariate analysis revealed that risk factors for the presence of HCV RNA in CVL fluid were HCV viremia (odds ratio [OR], 16.81; P = .02) and HIV-1 RNA in CVL fluid (OR, 19.87; P = .02). This observation suggests local interactions between HIV-1 and HCV in the genital tract compartment. There was no correlation between HCV RNA in CVL fluid and CD4, CD8, or CD3 cell counts, HIV-1 RNA viremia, the number of leukocytes in CVL fluid, or HIV-1 therapy. Furthermore, in 3 of 5 analyzed patients who had a detectable CVL HCV RNA load, we found viral variants differing in the 5′ untranslated region that were present neither in plasma nor in peripheral-blood mononuclear cells.
Conclusions
Our observations point to the importance of the genital tract compartment, in which local HCV replication could be facilitated by local HIV-1 replication.
doi:10.1086/491742
PMCID: PMC3164119  PMID: 16206070
3.  Racial/Ethnic Differences in Spontaneous HCV Clearance in HIV Infected and Uninfected Women 
Digestive diseases and sciences  2012;58(5):1341-1348.
Background/Aims
Among individuals without human immunodeficiency virus (HIV), African Americans have lower spontaneous clearance of hepatitis C virus (HCV) than Caucasians, and women have higher clearance than men. Few studies report racial/ethnic differences in acute HCV in HIV infected, or Hispanic women. We examined racial/ethnic differences in spontaneous HCV clearance in a population of HCV mono- and co-infected women.
Methods
We conducted a cross sectional study of HCV seropositive women (897 HIV infected and 168 HIV uninfected) followed in the US multicenter, NIH-funded Women's Interagency HIV Study (WIHS), to determine the association of race/ethnicity with spontaneous HCV clearance, as defined by undetectable HCV RNA at study entry.
Results
Among HIV and HCV seropositive women, 18.7 % were HCV RNA negative, 60.9 % were African American, 19.3 % Hispanic and 17.7 % Caucasian. HIV infected African American women were less likely to spontaneously clear HCV than Hispanic (OR 0.59, 95 % CI 0.38–0.93, p = 0.022) or Caucasian women (OR 0.57, 95 % CI 0.36–0.93, p = 0.023). Among HIV uninfected women, African Americans had less HCV clearance than Hispanics (OR 0.18, 95 % CI 0.07–0.48, p = 0.001) or Caucasians (OR 0.26, 95 % CI 0.09–0.79, p = 0.017). There were no significant differences in HCV clearance between Hispanics and Caucasians, among either HIV infected (OR 0.97, 95 % CI 0.57–1.66, p = 0.91) or uninfected (OR 1.45, 95 % CI 0.56–3.8, p = 0.45) women.
Conclusions
African Americans were less likely to spontaneously clear HCV than Hispanics or Caucasians, regardless of HIV status. No significant differences in spontaneous HCV clearance were observed between Caucasian and Hispanic women. Future studies incorporating IL28B genotype may further explain these observed racial/ethnic differences in spontaneous HCV clearance.
doi:10.1007/s10620-012-2486-8
PMCID: PMC3663918  PMID: 23179159
African American; Hispanic; Acute hepatitis C; Female
4.  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
5.  Opioids and HIV/HCV Infection 
Since human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same modes of transmission and common risk factors for infection, co-infections with HIV and HCV are frequently found in injection drug users (IDUs). IDUs represent one of the largest reservoirs of HIV as well as HCV in the United States. These two pathogens are also likely to be responsible for the highest infectious disease morbidity and mortality rates among IDUs. IDUs frequently involve the abuse of heroin, the most common abused opiate. Opiates have been suggested to have a cofactor role in the immunopathogenesis of HIV disease, as they have the potential to compromise host immune responses and enhances microbial infections. Although in vitro studies have yielded relatively agreeable data that morphine, the active metabolite of heroin, exacerbate HIV infection/replication, epidemiologic studies as well as in vivo non-human primate investigations on the impact of opiate abuse on HIV disease progression have yielded the conflicting data. Given immunomodulation and immunocompromising effect as well as demonstrated impact to enhance HIV replication in vitro, it is reasonable to believe that opiate abuse is a facilitator in HIV and/or HCV disease progression. However, much remain to be learned about the mechanisms of opiate-mediated broad influence on host immunity and viral expression. Thus, more extensive studies are needed in order to determine the effects of different conditions of opiate abuse and to define the understanding of the role of opiate in modulating HIV and/ or HCV disease progression.
doi:10.1007/s11481-011-9296-1
PMCID: PMC3937260  PMID: 21755286
Opioids; Heroin; Morphine; Methadone; HIV; HCV
6.  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
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.  Hepatitis C virus infection and biological false-positive syphilis tests 
Background
The diagnosis of syphilis requires two-step serological testing. Not infrequently, sensitive screening tests are reactive but are not confirmed by more specific confirmatory tests yielding a biological false positive (BFP). This study sought to describe the prevalence of BFP in a large population of hepatitis C virus (HCV)-infected and uninfected women.
Methods
A cross-sectional serosurvey of HIV-seropositive and HIV-seronegative women enrolled in the Women’s Interagency HIV Study, a multicentre collaborative study of the natural history of HIV in women.
Results
Among HCV-infected women 4% had a BFP compared with 1% among those who were HCV uninfected (odds ratio (OR) 3.3, 95% CI 2.1 to 5.1). Controlling for both HIV infection and a history of intravenous drug use among all tests for syphilis a BFP also occurred more commonly in HCV-infected women compared with HCV-uninfected women (6% vs 1%, OR 7.62, 95% CI 1.9 to 12.5).
Conclusion
HCV infection is associated with various effects on immune function including alterations in serological test results. Women with HCV are more likely to have a BFP syphilis test than women without HCV.
doi:10.1136/sti.2009.040360
PMCID: PMC2981071  PMID: 20332367
9.  Blood-Borne Hepatitis in Opiate Users in Iran: A Poor Outlook and Urgent Need to Change Nationwide Screening Policy 
PLoS ONE  2013;8(12):e82230.
Objective
Iran has the highest rate of opiate use worldwide. However, most opiate users are not screened for hepatitis virus infections. This study aimed to provide accurate, detailed data on the size of the opiate user population at risk of developing these infections.
Method
This seroprevalence study was conducted in the city of Shiraz, southern Iran. All participants were screened for HBV, HCV and HIV infection. The data were analyzed with SPSS.
Result
Among 569 participants, 233 (40.9%) were injection drug users (IDU), 369 (64.8%) were heterosexual, 84 (14.7%) were bisexual and 15 (2.6%) were homosexual. One hundred nine (19.1%) were HCV antibody-positive, 18 (3.1%) were HBS antigen-positive, 72 (12.6%) were HBc antibody-positive and 23 (4%) were HIV-positive. Among IDU compared to non-IDU, positivity rates for HBS antigen (5.5 vs 1.4%), HBc antibody (22.7 vs 5.6%), HCV antibody (40.3 vs 4.4%) and HIV (7.7 vs 1.4%) were higher (P < 0.05). Most patients with HBV (80.7%) and HCV infection (83.4%) were HIV-negative. In the cumulative analysis, only history of imprisonment was a statistically significant determinant of infection by HCV or HBV in opiate users.
Conclusion
The current policy of screening only HIV-positive drug users for HBV and HCV in Iran misses most cases of HBV and HCV infection. We therefore recommend urgent revision of the nationwide protocol by the Ministry of Health in Iran to implement routine screening of all opiate users and especially IDU for these viruses, regardless of their HIV status.
doi:10.1371/journal.pone.0082230
PMCID: PMC3846675  PMID: 24312645
10.  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
11.  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
12.  Hepatitis C virus infection is associated with insulin resistance among older adults with or at risk of HIV infection 
AIDS (London, England)  2007;21(5):633-641.
Objectives
To determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection.
Design
A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus.
Methods
HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes].
Results
Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4 h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association.
Conclusion
The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals.
doi:10.1097/QAD.0b013e3280464db7
PMCID: PMC2423380  PMID: 17314526
Hepatitis C virus; HIV; impaired glucose tolerance; insulin resistance; obesity; type 2 diabetes
13.  Antiretroviral Therapy Exposure and Insulin Resistance in the Women’s Interagency HIV Study 
Background
Evidence suggesting an increased risk of cardiovascular disease in HIV-infected individuals has heightened the need to understand the relation of HIV infection, antiretroviral therapy use, and non–HIV-related factors with insulin resistance (IR).
Methods
Prospective study of 1614 HIV-infected and 604 HIV-uninfected participants from the Women’s Interagency HIV Study between October 2000 and March 2007. Homeostasis model assessment (HOMA)–estimated IR at 11,019 semiannual visits.
Results
HIV-infected women reporting highly active antiretroviral therapy (HAART) had higher median HOMA than HIV-uninfected women {1.20 [95% confidence interval (CI): 1.11 to 1.30] times higher for those reporting protease inhibitor–containing HAART; 1.10 (95% CI: 1.01 to 1.20) times higher for those reporting non–protease inhibitor–containing HAART}. Among HIV-infected, cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs) of >3 years was associated with HOMA 1.13 (95% CI: 1.02 to 1.25) times higher than the HOMA without any cumulative NRTI exposure. Cumulative exposure to the NRTI stavudine of >1 year was associated with HOMA 1.15 (95% CI: 1.05 to 1.27) times higher than the HOMA without any cumulative stavudine use. Family history of diabetes, hepatitis C virus seropositivity, higher body mass index, or reporting menopause was associated with higher HOMA.
Conclusions
Longer cumulative exposure to NRTI; in particular, stavudine is associated with greater IR in HIV-infected women.
PMCID: PMC2889144  PMID: 19186350
antiretroviral therapy; HIV; HOMA; insulin resistance; nucleoside reverse transcriptase inhibitor; protease inhibitor
14.  Oral and Systemic Health Correlates of HIV-1 Shedding in Saliva 
Journal of dental research  2010;89(10):1074-1079.
The relationship among oral and systemic health and HIV shedding in saliva is not well understood. We hypothesized that oral and systemic health are associated with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants enrolled in the Women’s Interagency HIV Study (WIHS) was collected at repeated visits over a 5-1/2 year study period (October 1998 through March 2004) and was evaluated for HIV-1 RNA. Demographic, lifestyle, systemic and oral health characteristics were evaluated as possible correlates of salivary HIV-1 shedding. Multivariate models showed significantly increased risk of HIV-1 shedding in saliva as blood levels of CD4 cell counts decreased (p<0.0001) and HIV RNA increased (p<0.0001). Diabetes (p=0.002) and high proportion of gingival bleeding sites (p=0.01) were associated with increased likelihood, while antiretroviral therapy (p=0.0003) and higher levels of stimulated saliva flow rates (p=0.02) were associated with a lower likelihood of HIV-1 RNA shedding in saliva.
doi:10.1177/0022034510375290
PMCID: PMC2970637  PMID: 20671205
HIV-1 Shedding; Saliva; Oral Health
15.  Oral and Systemic Health Correlates of HIV-1 Shedding in Saliva 
Journal of Dental Research  2010;89(10):1074-1079.
The relationship among oral and systemic health and HIV shedding in saliva is not well-understood. We hypothesized that oral and systemic health are associated with HIV shedding in saliva of HIV-infected women. Saliva from 127 participants enrolled in the Women’s Interagency HIV Study (WIHS) was collected at repeated visits over a 5½-year study period (October 1998 through March 2004) and was evaluated for HIV-1 RNA. Demographic, lifestyle, and systemic and oral health characteristics were evaluated as possible correlates of salivary HIV-1 shedding. Multivariate models showed significantly increased risk of HIV-1 shedding in saliva as blood levels of CD4 cell counts decreased (p < 0.0001) and HIV RNA increased (p < 0.0001). Diabetes (p = 0.002) and a high proportion of gingival bleeding sites (p = 0.01) were associated with increased likelihood, while anti-retroviral therapy (p = 0.0003) and higher levels of stimulated saliva flow rates (p = 0.02) were associated with a lower likelihood of HIV-1 RNA shedding in saliva.
doi:10.1177/0022034510375290
PMCID: PMC2970637  PMID: 20671205
HIV-1 shedding; saliva; oral health
16.  Evaluating the Impact of Hepatitis C Virus (HCV) on Highly Active Antiretroviral Therapy–Mediated Immune Responses in HCV/HIV-Coinfected Women: Role of HCV on Expression of Primed/Memory T Cells 
The Journal of infectious diseases  2006;193(9):1202-1210.
Objective
To evaluate the impact of hepatitis C virus (HCV) on the immune system before receipt of highly active antiretroviral therapy (HAART) and on immune recovery after receipt of HAART among human immunodeficiency virus (HIV)/HCV–coinfected women enrolled in the Women’s Interagency HIV Study.
Methods
The study included 294 HIV-infected women who initiated HAART and attended 2 follow-up visits. The women were grouped on the basis of positive HCV antibody and HCV RNA tests. There were 148 women who were HCV antibody negative, 34 who were HCV antibody positive but RNA negative, and 112 who were HCV antibody and RNA positive. Immune recovery was measured by flow-cytometric assessment for markers of activation and maturation on CD4+ and CD8+ T cells. Data analysis used repeated measures of variance.
Results
HIV/HCV coinfection is associated with an increased number of CD4+ and CD8+ primed/memory T cells. HIV/HCV coinfection, however, did not affect any further decreases in CD4+ or CD4+ and CD8+ naive/memory T cell counts or enhanced T cell activation. HIV/HCV coinfection also did not affect HAART responses in the CD4+ and CD8+ T cell compartment.
Conclusions
HCV does not affect immune responses to HAART in HIV/HCV–coinfected individuals but is associated with an expansion of CD4+ and CD8+ memory T cell subsets. Functional impairment in the CD4+ and CD8+ T cell compartments still needs to be assessed in coinfected patients.
doi:10.1086/500843
PMCID: PMC3126663  PMID: 16586355
17.  Human immunodeficiency virus–hepatitis C virus co-infection in pregnant women and perinatal transmission to infants in Thailand 
Summary
Objectives
The objectives of this study were to assess the prevalence and factors associated with hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected and -uninfected Thai pregnant women and the rate of HCV transmission to their infants.
Patients and methods
Study subjects included 1435 HIV-infected pregnant women and their infants, enrolled in a perinatal HIV prevention trial, and a control group of 448 HIV-uninfected pregnant women. Women were screened for HCV antibodies with an enzyme immunoassay. Positive results were confirmed by recombinant immunoblot and HCV RNA quantification. Infants were tested for HCV antibodies at 18 months or for HCV RNA at between 6 weeks and 6 months.
Results
Of the HIV-infected women, 2.9% were HCV-infected compared to 0.5% of HIV-uninfected women (p = 0.001). Only history of intravenous drug use was associated with HCV infection in HIV-infected women. Ten percent of infants born to co-infected mothers acquired HCV. The risk of transmission was associated with a high maternal HCV RNA (p = 0.012), but not with HIV-1 load or CD4 count.
Conclusions
Acquisition of HCV through intravenous drug use partially explains the higher rate of HCV infection in HIV-infected Thai women than in HIV-uninfected controls. Perinatal transmission occurred in 10% of infants of HIV–HCV-co-infected mothers and was associated with high maternal HCV RNA.
doi:10.1016/j.ijid.2009.09.002
PMCID: PMC2886172  PMID: 20047847
HIV; HCV; Risk factors; Perinatal transmission; Intravenous drug use; Thailand
18.  Cytomegalovirus Immunoglobulin G Antibody Is Associated With Subclinical Carotid Artery Disease Among HIV-Infected Women 
The Journal of Infectious Diseases  2012;205(12):1788-1796.
Background. Cytomegalovirus (CMV) infection has been implicated in immune activation and accelerated progression of immunodeficiency from human immunodeficiency virus (HIV) coinfection. We hypothesized that CMV is associated with vascular disease in HIV-infected adults.
Methods. In the Women's Interagency HIV Study, we studied 601 HIV-infected and 90 HIV-uninfected participants. We assessed the association of CMV immunoglobulin G (IgG) level with carotid artery intima-media thickness, carotid artery distensibility, Young's elastic modulus, and blood pressures. Multivariable models adjusted for age, race/ethnicity, smoking, diabetes, and body mass index.
Results. Mean CMV IgG levels were higher in HIV-infected women compared with HIV-uninfected women (P < .01). Among HIV-infected women, higher CMV IgG level was associated with decreased carotid artery distensibility (P < .01) and increased Young's modulus (P = .02). Higher CMV IgG antibody level was associated with increased prevalence of carotid artery lesions among HIV-infected women who achieved HIV suppression on antiretroviral therapy, but not among viremic or untreated HIV-infected women. Adjustment for Epstein–Barr virus antibody levels and C-reactive protein levels had no effect on the associations between CMV IgG levels and vascular parameters.
Conclusions. Cytomegalovirus antibody titers are increased in HIV-infected women and associated with subclinical cardiovascular disease. Host responses to CMV may be abnormal in HIV infection and associated with clinical disease.
doi:10.1093/infdis/jis276
PMCID: PMC3415890  PMID: 22492856
19.  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
20.  Testosterone and Abnormal Glucose Metabolism in an Inner-City Cohort 
Journal of men's health  2012;9(3):10.1016/j.jomh.2012.03.010.
Background
Low testosterone (T) has been associated with insulin resistance and diabetes mellitus (DM) among men in population-based studies. These studies included racially diverse men, but did not target for inclusion individuals with opiate use, Hepatitis C Virus (HCV) infection, or Human Immunodeficiency Virus (HIV) infection, which disproportionately affect inner-city populations and may alter the relationship between T and DM.
Methods
We studied the association between free T (FT) and abnormal glucose metabolism among male participants in the Study of HIV, Injection Drug Use, Nutrition, and Endocrinology (SHINE). We used logistic regression to examine the relationship between log FT and both insulin resistance and prediabetes/DM.
Results
Of 175 men, 43 (24.6%) had low FT (FT < 52 pg/mL). There were more men in the low FT group on methadone maintenance (39.5% v. 15.2%, p=.001), but there was no difference in FT by HIV or HCV status. Overall, 23 men (13.1%) had prediabetes/DM, which was unrelated to FT (OR of prediabetes/DM for each log increase in FT = 0.56, 95% CI 0.13–2.41). FT was also not related to insulin resistance.
Conclusions
The prevalence of hypogonadism was high in this inner-city cohort and was associated with methadone use. However, low FT was not related to insulin resistance or prediabetes/DM. Continued work to identify diabetes risk factors among inner-city populations will help determine targets for intervention to reduce diabetes incidence. Treatment trials of testosterone to reduce diabetes among hypogonadal men may be of particular relevance to opiate users, many of whom are hypogonadal.
doi:10.1016/j.jomh.2012.03.010
PMCID: PMC3809764  PMID: 24174995
Testosterone; Diabetes; Insulin Resistance; Methadone
21.  The Relationship Between Race and HIV-Distal Sensory Polyneuropathy in a Large Cohort of US Women 
Journal of the Neurological Sciences  2011;315(1-2):129-132.
Introduction
HIV-distal sensory polyneuropathy (HIV-DSPN) is a common complication of HIV infection, yet race as a potential risk factor is not known.
Methods
Between April and October 2009, as part of the NIH Women’s Interagency HIV Study (WIHS), 1414 women, 973 of whom were HIV-infected, were clinically evaluated for peripheral neuropathy. Utilizing available clinical, laboratory, and sociodemographic variables, we conducted a cross-sectional analysis of factors associated with HIV-DSPN. Multivariable logistic regression was used to examine factors independently associated with HIV-DSPN.
Results
36% of HIV-infected women met our definition of HIV-DSPN. 41.3% of African Americans, 34.8% of Whites and 24.7% of Hispanics had DSPN. Age, Hepatitis C-co-infection, and diabetes were each significantly associated with HIV-DSPN. After controlling for age, diabetes, Hepatitis C co-infection, alcohol use, current dideoxy-nucleoside reverse transcriptase inhibitor use, current CD4 count, and plasma HIV viral load, HIV-DSPN was significantly associated with ethnicity; the odds ratio was 1.67 (p=0.001) in African-Americans compared to other racial groups.
Conclusion
The prevalence of HIV-DSPN in women was lower than reported in prior studies. The likelihood of HIV-DSPN was higher in African-Americans compared to other racial groups. HIV-DSPN was more common in those co-infected with Hepatitis C, older individuals, and diabetics. Further prospective studies are needed to explore the relationship between gender, race, and HIV-DSPN, and the mechanistic basis for racial differences.
doi:10.1016/j.jns.2011.11.009
PMCID: PMC3299869  PMID: 22123155
HIV-associated sensory polyneuropathy; African-Americans; race; women; gender; diabetes; Hepatitis C
22.  Occurrence of Hepatitis C Virus infection in type 2 diabetic patients attending Plateau state specialist hospital Jos Nigeria 
Virology Journal  2009;6:98.
Background
Glucose intolerance is observed more in patients with HCV infection compared with control subjects with liver disease, Initial studies suggested that Hepatitis C virus infection may be an additional risk factor for the development of diabetes mellitus. This study was therefore carried out to determine the correlation of HCV infection and diabetes.
Methods
Three hundred (300) confirmed type 2 diabetic patients were screened for hepatitis C virus antibodies at the Plateau state specialist hospital, Jos, using Grand diagnostic test strip. Questionnaire comprising of age, sex, family history on diabetes, duration of disease and marital status were issued to subjects.
Results
Overall result showed that the prevalence rate of HCV infection was 33(11%). In response to diabetic status, females subjects had a higher prevalence of 178(59.3%) compared to males 122(40.7%). Those aged 47–57 recorded the highest seroprevalence 10(30.3%) to the Hepatitis C Virus, while Patients without family history of diabetes showed a higher seroprevalence of 13(39.4%). Subjects who never had any blood transfusion recorded a prevalence rate of 6(18.2%). Marital status showed no significant difference [(P = 0.275; P.0.05)]. Considering duration of developing diabetes, patients within the range of 1–10 years diabetic status recorded the highest prevalence rate 25(75.8%) compared to other ranges considered.
Conclusion
This study hence, suggests a relatively strong association between HCV infection and diabetes, this therefore call for an urgent approach strategy in the control and management of this disease of the endocrine system.
doi:10.1186/1743-422X-6-98
PMCID: PMC2714490  PMID: 19586535
23.  Prevalence of type 2 diabetes in Algerian patients with hepatitis C virus infection 
AIM: To investigate the prevalence of, and risk factors for, diabetes mellitus (DM) in Algerian patients with chronic hepatitis C virus (HCV) infection and in a control group.
METHODS: A cross-sectional study was undertaken. A total of 416 consecutive patients with viral chronic hepatitis attending the Internal Medicine Department of the University Hospital Center Touhami Benflis in Batna [290 HCV-infected and 126 hepatitis B virus (HBV)-infected patients] were prospectively recruited.
RESULTS: The prevalence of DM was higher in HCV-infected patients in comparison with HBV-infected patients (39.1% vs 5%, P < 0.0001). Among patients without cirrhosis, diabetes was more prevalent in HCV-infected patients than in HBV-infected patients (33.5% vs 4.3%, P < 0.0001). Among patients with cirrhosis, diabetes was more prevalent in HCV-infected patients, but the difference was not significant (67.4% vs 20%, P = 0.058). The logistic regression analysis showed that HCV infection [odds ratio (OR) 4.73, 95% CI: 1.7-13.2], metabolic syndrome (OR 12.35, 95% CI: 6.18-24.67), family history of diabetes (OR 3.2, 95% CI: 1.67-6.13) and increased hepatic enzymes (OR 2.22, 95% CI: 1.1-4.5) were independently related to DM in these patients.
CONCLUSION: The high prevalence of diabetes in HCV-infected patients, and its occurrence at early stages of hepatic disease, suggest that screening for glucose abnormalities should be indicated in these patients.
doi:10.3748/wjg.v16.i27.3427
PMCID: PMC2904891  PMID: 20632447
Prevalence; Hepatitis C virus; Hepatitis B virus; Diabetes mellitus; Algeria
24.  Negative-Strand Hepatitis C Virus (HCV) RNA in Peripheral Blood Mononuclear Cells from Anti-HCV–Positive/HIV-Infected Women 
The Journal of Infectious Diseases  2006;195(1):124-133.
Background
Hepatitis C virus (HCV) has been reported to replicate in peripheral blood mononuclear cells (PBMCs), particularly in patients coinfected with HCV and human immunodeficiency virus (HIV). However, there are limited data regarding the prevalence of and the factors associated with extrahepatic replication.
Methods
The presence of negative-strand HCV RNA in PBMCs was evaluated by a strand-specific assay for 144 anti-HCV–positive/HIV-infected women enrolled in the Women’s Interagency HIV Study. One to 5 PBMC samples obtained from each woman were tested. Multivariate analyses were used to assess for associations with the clinical and demographic characteristics of the women.
Results
Negative-strand HCV RNA was detected in 78 (25%) of 315 specimens, and, for 61 women (42%), ≥1 specimen was found to have positive results. The presence of negative-strand HCV RNA in PBMCs was significantly positively associated with an HCV RNA plasma level of ≥6.75 log copies/mL (P =.04) and consumption of ≥7 alcoholic drinks per week (P =.02). It was also negatively associated with injection drug use occurring in the past 6 months (P =.03). A negative association with a CD4+CD38+DR+ cell percentage of >10% and a positive association with acquired immunodeficiency syndrome were borderline significant (P =.05).
Conclusions
HCV replication in PBMCs is common among HIV-coinfected women and appears to be a dynamic process related to lifestyle, virologic, and immunologic factors.
doi:10.1086/509897
PMCID: PMC3319123  PMID: 17152016
25.  Effects of hepatitis C and HIV on cognition in women: Data from the Women’s Interagency HIV Study 
Objective
To compare neuropsychological scores in women infected with HIV, women infected with both HIV and hepatitis C, and uninfected subjects.
Background
Some, but not all, studies have demonstrated that dual infection with HCV and HIV has worse effects on cognition than infection with HIV alone.
Design/Methods
The Women’s Interagency HIV Study (WIHS) is an ongoing prospective study of the natural history of HIV in women where participants are reevaluated every 6 months. In a cross-sectional analysis, we evaluated the effects of active HIV and HCV-infections on scores on symbol-digit test (SDMT), the Stroop interference test, and trails A and B after controlling for age, ethnicity, education, depression, liver disease, and current or past substance abuse.
Results
Data were available for 1338 women – 17.8 % had detectable hepatitis C virus and 67% were HIV-seropositive. In fully adjusted general linear models, HCV viremia was not associated with scores on any of the cognitive tests.
Conclusion
In this large sample of women, active HCV infection was not associated with scores on a small battery of neuropsychological tests.
doi:10.1097/QAI.0b013e318240566b
PMCID: PMC3319079  PMID: 22107817
Hepatitis C; HIV; neurocognition; women

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