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J Clin Virol. Author manuscript; available in PMC Nov 8, 2012.
Published in final edited form as:
PMCID: PMC3493623
NIHMSID: NIHMS45707
Factors associated with hepatitis C viremia in a large cohort of HIV-infected and - uninfected women
Eva A. Operskalski,a* Wendy J. Mack,b Howard D. Strickler,c Audrey French,d Michael Augenbraun,e Phyllis C. Tien,f Maria C. Villacres,a LaShonda Y. Spencer,a Marina DeGiacomo,a and Andrea Kovacsa
aMaternal Child and Adolescent Center for Infectious Diseases and Virology, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
bDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
cAlbert Einstein College of Medicine, Bronx, NY, USA
dCORE Center/Stroger (Cook County) Hospital, Rush Medical College, Chicago, IL, USA
eDepartment of Medicine, State University of New York, Health Sciences Center at Brooklyn, NY, USA
fDepartment of Medicine, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
*Corresponding author at: Maternal Child and Adolescent Center for Infectious Diseases and Virology, 1640 Marengo Street, Suite 300, Los Angeles, CA 90033. Tel.: +1 323-226-2226; fax: +1 323-226-2505. E-mail address:eva/at/usc.edu
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.
Keywords: Hepatitis C, Hepatitis C RNA levels, Hepatitis C viremia, HIV/hepatitis C virus coinfection
Approximately four million people in the U.S. are infected with hepatitis C virus (HCV) (Armstrong et al., 2006). Among high-risk populations (hemophiliacs, injection drug users, HIV-infected patients), HCV prevalence is 30–98% (Mohsen et al., 2002).
Following initial infection, HCV viremia clears in approximately 20% of individuals, ranging from 15% of transfusion recipients to 45% of infants and young women (Thomas and Seeff, 2005). Factors associated with persistence include older age, male gender, African-American race, immunosuppression, HLA subtypes and polymorphisms, and blunted innate immune response (Thomas and Seeff, 2005). HIV coinfection is associated with reduced HCV clearance, whereas hepatitis B virus (HBV) is associated with higher clearance (Zhang et al., 2006).
Compared with the general population, HIV co-infected individuals have higher plasma HCV RNA levels (Zhang et al., 2006), and more HCV-associated complications (Thomas and Seeff, 2005). Since the introduction of highly active anti-retroviral therapy (HAART), HCV has become a major source of morbidity and mortality in co-infected individuals (Winnock et al., 2004).
While most HCV studies evaluated predominantly male populations (Mohsen et al., 2002; Thomas and Seeff, 2005; Zhang et al., 2006), understanding factors influencing persistent HCV infection in women is important in considering candidates for anti-HCV therapy. Chronically-infected patients with lower HCV viral loads have better response to therapy (NIH Consensus Development Conference Statement, 2002; Torriani et al., 2004) and are less likely to transmit HCV (Chayama et al., 1995; Thomas et al., 1998; Hisada et al., 2000). To understand risk factors for HCV viremia and viral load, we evaluated HCV-seropositive women at entry into the Women's Interagency HIV Study (WIHS).
2.1. Participants
This investigation included 1,049 (882 HIV-infected, 167 HIV-uninfected) HCV-seropositive women at entry into WIHS. Briefly, 2,059 HIV-infected and 569 uninfected women were enrolled at six sites (Los Angeles and San Francisco, CA; Washington, DC; Brooklyn and Bronx, NY; Chicago, IL) in October 1994–November 1995 (Bacon et al., 2005). This cohort was augmented in October 2001–November 2002 (738 HIV-infected, 406 uninfected). The WIHS protocol was approved by local institutional review boards; informed consent was obtained.
2.2. Laboratory methods at entry visit
Plasma HIV RNA levels were measured using the NASBA/NucliSens HIV RNA assay (bioMerieux, Durham, NC), in laboratories certified by the NIH National Institute of Allergy and Infectious Diseases Virology Quality Assurance Certification Program.
HCV and HBV serology were performed using standard commercial assays by local clinical laboratories. HBV serology included hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) and hepatitis B core antibody (anti-HBc).
HCV RNA was measured in 352 HCV-seropositive women using the COBAS Amplicor Monitor 2.0 assay (Roche Diagnostics, Branchburg, NJ) with a linear range of 600–700,000 IU/ml. All samples were diluted 1:10. Samples negative for HCV RNA were retested undiluted using the qualitative Amplicor 2.0 HCV assay, with a lower detection limit of 50 IU/ml (Roche Diagnostics). Positive undiluted samples were retested with the quantitative assay. All specimens>500,000 IU/ml were retested 1:100. Remaining HCV-seropositive women were tested using the real-time polymerase chain reaction (PCR) assay, COBAS Taqman (Roche Diagnostics), with a linear range of 10– 2.0×108 IU/m, after demonstrating concordance of results using the two assays. Specimens non-reactive by HCV quantitative and qualitative PCR were considered HCV RNA-negative. Women with undetectable HCV RNA were retested to confirm HCV-seropositivity by HCV 3.0 EIA (Ortho-Clinical Diagnostics, Raritan, NJ).
Lymphocyte subsets were measured using standard flow cytometry at local laboratories participating in the NIH Division of Acquired Immune Deficiency Syndrome Flow Cytometric Quality Assurance Program.
2.3. Statistical analysis
Logistic regression was used to relate HCV viremia to participant characteristics. Factors associated with HCV RNA level among HCV-viremic women were studied using ordinal logistic regression with a three-level outcome: >0–<5.0, 5.0–7.0, and >7.0 log10 copies/ml. The following characteristics were investigated: age, race, education, history of injection drug use (IDU), amphetamine, cocaine, crack/freebase cocaine, heroin, marijuana/hash use, IDU in last six months, lifetime number of sex partners, sex with injection drug user or HIV-infected male, history of sex for drugs, money, or shelter, alcohol use, current smoking, blood transfusion, and HBV and HIV status. For HIV-infected women, additional characteristics included AIDS, HIV therapy, HIV plasma RNA, and CD4 and CD8 counts. Multivariate models included independent variables with P<0.20 in univariate analyses.
The majority of HCV-seropositive women was over 35 years old, Black, had completed high school, and had serologic evidence of HBV infection (Table 1). Over 90% had used illicit drugs but most had not recently injected drugs. Among HCV-viremic women, the median log10 HCV RNA level was 6.3 copies/ml for HIV-infected women and 5.8 copies/ml for uninfected women. Only 4% of HIV-infected women had received HAART, as 90% were enrolled before HAART was generally available. Almost 25% had an HIV RNA level>100,000 copies/ml or CD4 count<200 cells/ml.
Table 1
Table 1
Baseline characteristics of 1,049 anti-HCV-positive women evaluated for presence and level of HCV viremia
Multivariate analysis of the presence of HCV viremia (Table 2) revealed positive associations for Black race, crack/freebase cocaine use, and smoking, and inverse associations with HBsAg and anti-HBc/anti-HBs positivity. There was no association with HIV status.
Table 2
Table 2
Factors associated with presence of HCV viremia among 1,049 HCV-seropositive women (882 HIV-infected and 167 HIV-uninfected) at baseline WIHS visit, multivariate analysisa
Multivariate analysis of factors associated with higher HCV RNA levels among the HCV-viremic women (Table 3) revealed that age>35 years, marijuana/hash use, smoking, and HIV infection were positively, while heroin was inversely associated with viremia levels.
Table 3
Table 3
Factors associated with level of HCV viremia among HIV-infected and HIV-uninfected women at baseline WIHS visit, multivariate ordinal logistic regression analyses using log HCV RNA level >0 to <5.0 as reference levela.
Among HIV-infected women (Table 4), presence of HCV viremia was positively associated with Black race, smoking, and HIV plasma RNA>100,000 copies, and inversely associated with HBsAg antigenemia. The associations with HCV levels observed for the entire cohort generally remained (Table 5). In addition, sex with an injection drug user was positively associated, while amphetamine use and CD8 counts<800 were inversely associated with viremia levels.
Table 4
Table 4
Factors associated with presence of HCV viremia among 882 HIV-infected HCV-seropositive women at baseline WIHS visit, multivariate analysisa
Table 5
Table 5
Factors associated with level of HCV viremia among HIV-infected women at baseline WIHS visit, multivariate ordinal logistic regression analyses using log HCV RNA level >0 to <5.0 as reference levela
In this largest cross-sectional study of HCV-seropositive women, age>35 years, Black race, drug use, smoking, and HIV and HBV co-infections were associated with presence and level of HCV viremia.
Viremic women >35 years old had higher HCV RNA levels; age had no effect on presence of HCV. These observations support reports among blood donors, drug users and women (Thomas et al., 2001; Busch et al., 2006; Fishbein et al., 2006), although one study found no association of HCV RNA levels with age (Sherman et al., 1993). Age-related immunity may not affect persistence/clearance of infection, but may reduce control of established infection.
An interaction of HIV with HCV infection has been observed (Dieterich, 1999; Winnock et al., 2004). Higher HCV RNA is associated with HIV positivity and HIV RNA levels (Sherman et al., 1993; Cribier et al., 1995; Thomas et al., 2001; Fishbein et al., 2006). Consistent with earlier reports (Daar et al., 2001; Thomas et al., 2001), we found a positive association between presence of HCV viremia and HIV RNA only at HIV RNA>100,000 copies/ml, suggesting that advanced HIV disease and resulting immunosuppression influence HCV viremia. Alternatively, HCV infection may more likely occur in advanced HIV disease.
Black women were more likely to be HCV-viremic, consistent with reports in other populations (Alter et al., 1999; Villano et al., 1999; Thomas et al., 2000a; Busch et al., 2006), although one study found no such association after controlling for HIV infection (Piasecki et al., 2004). In HCV treatment studies, Blacks have lower viral response to therapy (Brau et al., 2006). HCV persistence is associated with class II HLAs and HLA-DQB1*0301 may be more strongly associated with HCV clearance in Blacks (Thio et al., 2001). The racial effect we observed might be due to class II allele differences.
Smoking increased the likelihood of HCV viremia, which may be related to immunosuppressive effects of smoking/nicotine (Nair et al., 1990; McAllister-Sistilli et al., 1998; Ouyang et al., 2000). Smoking is associated with higher prevalence and incidence of HPV infection among HIV-infected women, suggesting that smoking during HIV infection alters the natural history of other viruses (Minkoff et al., 2004).
In vivo and in vitro studies of HIV and cocaine found decreased antimicrobial activity, cytokine production (Baldwin et al., 1997), lymphocyte proliferation and CD4/CD8 ratio, and increased HIV replication (Thomas et al., 1996; Roth et al., 2002). These findings in HIV may relate the association of HCV viremia with crack cocaine we observed. Similarly, women who used marijuana had higher HCV RNA levels, which may reflect known effects of cannabinoids on the function of T, B, and NK cells and macrophages (Friedman et al., 2003), and suppression of host resistance to infections (Joy et al., 1999).
The negative association between heroin use and levels of HCV viremia is puzzling in view of the opiate-mediated suppression of immune cells (Friedman et al., 2003). However, opiates may have anti-inflammatory effects through increased TGF-β and decreased TNF-α and IFN-γ (Peterson et al., 1987; Chao et al., 1992; Chao et al., 1993). If inflammation favors HCV replication, this may partially explain heroin's protective effect. Our finding that illicit drugs varied in their effects on HCV viremia supports reports that immunomodulatory effects of psychotropic drugs either enhance or suppress infections by modulating T-helper activity (Friedman et al., 2003).
That women with evidence of current or resolved HBV infection were less likely to be HCV-viremic supports a reciprocal viral interaction (Thomas et al., 2000a; Thomas et al., 2000b; Jardi et al., 2001; Piasecki et al., 2004; Sagnelli et al., 2006).
Associations of HCV viremia with modifiable risk factors (smoking and illicit drug use) have important clinical and public health implications. In addition to our findings, hepatotoxicity of cigarette smoke and progression of fibrosis with marijuana use occur among patients with chronic HCV infection (Pessione et al., 2001; Hezode et al., 2003, Hezode et al., 2005). Eliminating tobacco and recreational drugs may lead to less severe histological lesions and decreased HCV viremia, an important indicator of response to therapy (NIH Consensus Development Conference, 2002; Torriani et al., 2004). Similarly, because patients with lower HCV viral loads are less likely to transmit HCV (Chayama et al, 1995; Thomas et al., 1998; Hisada et al., 2000), it may be beneficial to aggressively encourage HCV-viremic patients and their sexual partners to stop smoking and drug use.
This study had some limitations. We used baseline data and assume that HCV viremia reflects chronic, not recent, infection. Although we do not know date of HCV infection or when drug-using women started injecting (a good proxy for time of HCV infection), it is likely to have been several years before study entry. This seems reasonable since 92% of the women reported past drug use, but most had not recently injected. Nevertheless, the factors for which we found associations were, or most likely were, present at the time of clearance (race, drug use, HBV infection, and smoking). Although HCV RNA levels are relatively stable in chronic HCV infection (Gordon et al, 1998; Thomas et al., 2000b; Yeo et al., 2001), a recent study reported HCV RNA levels increased over a 2-year period (Fishbein et al., 2006). The replication patterns in HBV/HCV co-infection are widely divergent and have dynamic profiles, making a longitudinal evaluation of both viruses essential (Raimondo et al., 2006). Although in injection drug users, HCV and HBV infections usually predate HIV infection (Villano et al., 1999), it would be important to establish the timing of these infections to elucidate the observed relationships. Finally, our identification of factors associated with high and low HCV RNA levels was constrained by small numbers. Nonetheless, this report identifies factors associated with HCV viremia in the largest cohort of women of which we are aware.
In conclusion, the relationships of demographic, lifestyle, viral, and immunologic factors with HCV viremia in women are complex. HIV RNA level, age, smoking and Black race were the strongest predictors of HCV viremia. Because modifiable factors affect HCV viremia, HCV-infected women should be aggressively counseled against cigarette smoking and drug use. Eliminating such factors may result in lower rates of HCV chronicity, lower HCV viremia levels, reduced risk of sexual and vertical transmission, and improved response to HCV therapy.
Acknowledgements
This study was supported by grants RO1 AI052065 (AK) and RO1-AI0577006 (HS) from the National Institute of Allergy and Infectious Diseases). Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases with supplemental funding from the National Cancer Institute and the National Institute on Drug Abuse (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590). Funding is also provided by the National Institute of Child Health and Human Development (UO1-CH-32632) and the National Center for Research Resources (MO1-RR-00071, MO1-RR-00079, MO1-RR-00083).
Abbreviations
anti-HBchepatitis B core antibody
anti-HBshepatitis B surface antibody
EIAenzyme-linked immunoassay
HAARThighly active anti-retroviral therapy
HBsAghepatitis B surface antigen
HBVhepatitis B virus
HCVhepatitis C virus
HIVhuman immunodeficiency virus
HLAhuman leukocyte antigen
IDUinjection drug use
IFNinterferon
NIHNational Institutes of Health
PCRpolymerase chain reaction
RNAribonucleic acid
TGFtransforming growth factor
TNFtumor necrosis factor
WIHSWomen's Interagency HIV Study

Footnotes
Conflict of interest Authors do not have conflicts of interest in relation to the present manuscript.
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  • Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–562. [PubMed]
  • Armstrong G, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–714. [PubMed]
  • Bacon MC, von Wyl V, Alden C, et al. The Women's Interagency HIV Study: an observational cohort brings clinical sciences to the bench. Clin Diagn Lab Immunol. 2005;12:1013–1019. [PMC free article] [PubMed]
  • Baldwin GC, Tashkin DP, Buckley DM, et al. Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am J Respir Crit Care Med. 1997;156:1606–1613. [PubMed]
  • Brau N, Bini EJ, Currie S, et al. Black patients with chronic hepatitis C have a lower sustained viral response rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this is not explained by more frequent dose reductions of intervveron and ribavirin. J Viral Hepat. 2006;13:242–249. [PubMed]
  • Busch MP, Glynn SA, Stramer SL, et al. Correlates of hepatitis C virus (HCV) RNA negativity among HCV-seropositive blood donors. Transfusion. 2006;46:469–475. [PubMed]
  • Chao CC, Hu S, Molitor TW, et al. Morphine potentiates transforming growth factor-beta release from human peripheral mononuclear cells cultures. J Pharmacol Exp Ther. 1992;262:19–24. [PubMed]
  • Chao CC, Molitor TW, Close K, Hu S, Peterson PK. Morphine inhibits the release of tumor necrosis factor in human peripheral mononuclear cell cultures. Int J Immunopharmacol. 1993;15:447–453. [PubMed]
  • Chayama K, Kobayashi M, Tsubota A, et al. Molecular analysis of intraspousal transmission of hepatitis C virus. J Hepatol. 1995;22:431–439. [PubMed]
  • Cribier B, Rey D, Schmitt C, Lang JM, Kirn A, Stoll-Keller F. High hepatitis C viremia and impaired antibody response in patients coinfected with HIV. AIDS. 1995;9:1131–1136. [PubMed]
  • Daar ES, Lynn H, Donfield S, et al. Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. J Acquir Immune Defic Syndr. 2001;26:466–472. [PubMed]
  • Dieterich DT. Hepatitis C virus and human immunodeficiency virus: Clinical issues in coinfection. Am J Med. 1999;107:79S–84S. [PubMed]
  • Fishbein DA, Lo Y, Netski D, Thomas DL, Klein RS. Predictors of hepatitis C virus RNA levels in a prospective cohort of drug users. J Acquir Immune Defic Syndr. 2006;41:471–476. [PubMed]
  • Friedman H, Newton C, Klein TW. Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev. 2003;16:209–219. [PMC free article] [PubMed]
  • Gordon SC, Dailey PJ, Silverman AL, et al. Sequential serum hepatitis C viral RNA levels longitudinally assessed by branched DNA signal amplification. Hepatology. 1998;28:1702–1706. [PubMed]
  • Hezode C, Lonjon I, Roudot-Thoraval F, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut. 2003;52:126–129. [PMC free article] [PubMed]
  • Hezode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology. 2005;42:63–71. [PubMed]
  • Hisada M, O'Brien TR, Rosenberg PS, Goedert JJ. for the Multicenter Hemophilia Cohort Study. Virus load and risk of heterosexual transmission of human immunodeficiency virus and hepatitis C virus by men with hemophilia. J Infect Dis. 2000;181:1475–1478. [PubMed]
  • Jardi R, Rodriguez F, Buti M, et al. Role of hepatitis B, C, and D viruses in dual and triple infection: Influence of viral genotypes and hepatitis B precore and basal core promotor mutations on viral replicative interference. Hepatology. 2001;34:404–410. [PubMed]
  • Joy JE, Watson SJ, Benson JA. Marijuana and medicine: Assessing the science base. Washington DC: National Academy Press; 1999.
  • McAllister-Sistilli CG, Caggiula AR, Knopf S, et al. The effects of nicotine on the immune system. Psychoneuroendocrinology. 1998;23:175–187. [PubMed]
  • Minkoff H, Feldman JG, Strickler HD, et al. Relationship between smoking and human papillomavirus infections in HIV-infected and -uninfected women. J Infect Dis. 2004;189:1821–1828. [PubMed]
  • Mohsen AH, Easterbrook P, Taylor CB, Norris S. Hepatitis C and HIV-1 coinfection. Gut. 2002;51:601–608. [PMC free article] [PubMed]
  • Nair MP, Kronfol ZA, Schwartz SA. Effects of alcohol and nicotine on cytotoxic function of human lymphocytes. Clin Immunol Immunopathol. 1990;54:396–409. [PubMed]
  • National Institutes of Health Consensus Development Conference Statement. [June 10–12, 2002];Management of hepatitis C. 2002 Available at: http://consensus.nih.gov/2002/2002HepatitisC2002116html.htm.
  • Ouyang Y, Virasch N, Hao P, et al. Suppression of human IL-1β, IL-2, IFN-γ, and TNF-α production by cigarette smoke extracts. J Allergy Clin Immunol. 2000;106:280–287. [PubMed]
  • Pessione F, Ramond MJ, Njapoum C, et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology. 2001;34:121–125. [PubMed]
  • Peterson PK, Sharp B, Gekker G, Brummitt C, Keane WF. Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. J Clin Invest. 1987;80:824–831. [PMC free article] [PubMed]
  • Piasecki BA, Lewis JD, Reddy KR, et al. Influence of alcohol use, race, and viral coinfections on spontaneous HCV clearance in a US veteran population. Hepatology. 2004;40:892–899. [PubMed]
  • Raimondo G, Brunetto MR, Pontisso P, et al. Longitudinal evaluation reveals a complex spectrum of virologic profiles in hepatitis B virus/hepatitis C virus-co-infected patients. Hepatology. 2006;43:100–107. [PubMed]
  • Roth MD, Tashkin DP, Choi R, et al. Cocaine enhances human immunodeficiency virus replication in a model of severe combined immunodeficient mice implanted with human peripheral blood leukocytes. J Infect Dis. 2002;185:701–705. [PubMed]
  • Sagnelli E, Coppola N, Marrocco C, et al. Hepatitis C virus superinfection in hepatitis B virus chronic carriers: a reciprocal viral interaction and a variable clinical course. J Clin Virol. 2006;35:317–320. [PubMed]
  • Sherman KE, O'Brien J, Gutierrez AG, et al. Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections. J Clin Microbiol. 1993;31:2679–2682. [PMC free article] [PubMed]
  • Thio CL, Thomas DL, Goedert JJ, et al. Racial differences in HLA class II associations with hepatitis C virus outcomes. J Infect Dis. 2001;184:16–21. [PubMed]
  • Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection. Host, viral, and environmental factors. JAMA. 2000a;284:450–456. [PubMed]
  • Thomas DL, Astemborski J, Vlahov D, et al. Determinants of the quantity of hepatitis C virus RNA. J Infect Dis. 2000b;181:844–851. [PubMed]
  • Thomas DL, Rich JD, Schuman P, et al. Multicenter evaluations of hepatitis C RNA levels among female injection drug users. J Infect Dis. 2001;183:973–976. [PubMed]
  • Thomas DL, Seeff LB. Natural history of hepatitis C. Clin Liver Dis. 2005;9:383–388. [PubMed]
  • Thomas DL, Shih JW, Alter HJ, et al. Effect of human immunodeficiency virus on hepatitis C virus infection in injecting drug users. J Infect Dis. 1996;174:690–695. [PubMed]
  • Thomas DL, Villano SA, Riester KA, et al. Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. J Infect Dis. 1998;177:1480–1488. [PubMed]
  • Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C Virus infection in HIV-infected patients. N Eng J Med. 2004;351:438–450. [PubMed]
  • Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology. 1999;29:908–914. [PubMed]
  • Winnock M, Salmon-Ceron D, Dabis F, Chene G. Interaction between HIV-1 and HCV infections: toward a new entity? J Antimicrob Chemother. 2004;53:936–946. [PubMed]
  • Yeo AET, Ghany M, Conry-Cantilena, et al. Stability of HCV-RNA level and its lack of correlation with disease severity in symptomatic chronic hepatitis C virus carriers. J Viral Hepat. 2001;8:256–263. [PubMed]
  • Zhang M, Rosenberg PS, Brown DL, et al. Correlates of spontaneous clearance of hepatitis C virus among people with hemophilia. Blood. 2006;107:892–897. [PubMed]