Progression of Platelet Counts in Treatment Naïve HIV/HCV Co-Infection

Jonathan E. Schelfhout, Danijela A. Stojanovic, Amy Houtchens, Heidi M. Crane, Edward R. Cachay, Elizabeth R. Brown, Sonia M. Napravnik, Mari M. Kitahata, Michael S. Saag, Peter W. Hunt, Teresa L. Kauf, Joseph A. C. Delaney

Department of Epidemiology, University of Washington, Seattle, WA.
Department of Medicine, University of Alabama at Birmingham, Birmingham, USA.
Department of Medicine, University of California at San Diego, San Diego, USA.
Department of Medicine, University of California at San Francisco, San Francisco, USA.
Department of Medicine, University of North Carolina, Chapel Hill, USA.
Division of Allergy & Infectious Disease, Department of Medicine, University of Washington, Seattle, USA.
Food and Drug Administration, Silver Spring, USA.
Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, USA.

DOI: 10.4236/wja.2013.31006                

Abstract

Background: Previous research has suggested an association between infection with hepatitis C virus (HCV) or with human immunodeficiency virus (HIV) and low platelet counts. This study estimates platelet count changes over time in HIV/HCV co-infected participants and compares them with the changes in platelet count among HIV mono-infected participants to test if HIV/HCV co-infection is associated with lower platelet counts. Methods: This retrospective cohort study included all HIV treatment naive patients from four sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort with platelet count measurements between 2002 and 2009. We conducted a mixed effects linear regression modeling the mean change in platelet count per year while adjusting for age, sex, race, baseline CD4 cell count, and site. Index date was the first platelet count after 2002, and participants were censored upon initiation of treatment for HIV or HCV. Results: There were 929 HIV/HCV co-infected and 3558 HIV mono-infected participants with a mean follow-up time of 1.2 years. HIV/HCV co-infected participants had on average a slighter lower platelet count at baseline (234,040 vs. 242,780/μL; p-value = 0.004), and a more rapid mean reduction per year (7230 vs. 3580/μL; p-value < 0.001) after adjusting for age, sex, baseline CD4 count. Conclusions: In treatment naive participants, HIV/HCV co-infection is associated with a more rapid decline in platelet count compared with HIV mono-infection.

Keywords

HCV; HIV; AIDS; Co-Infection; Platelet Count; Thrombocytopenia

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	K. E. Sherman, et al., “Hepatitis C Virus Prevalence among Patients Infected with Human Immunodeficiency Virus: A Cross-Sectional Analysis of the US Adult AIDS Clinical Trials Group,” Clinical Infectious Diseases, Vol. 34, No. 6, 2002，pp. 831-837. doi:10.1086/339042
[2]	L.-P. Deng, et al., “Impact of Human Immunodeficiency Virus Infection on the Course of Hepatitis C Virus Infection: A Meta-Analysis,” World Journal of Gastroenterology, Vol. 15, No. 8, 2009, pp. 996-1003. doi:10.3748/wjg.15.996
[3]	T.-Y. Chen, et al., “Meta-Analysis: Increased Mortality Associated with Hepatitis C in HIV-Infected Persons Is Unrelated to HIV Disease Progression,” Clinical Infectious Diseases, Vol. 49, No. 10, 2009, pp. 1605-1615. doi:10.1086/644771
[4]	H. K. Monga, et al., “Hepatitis C Virus Infection-Related Morbidity and Mortality among Patients with Human Immunodeficiency Virus Infection,” Clinical Infectious Diseases, Vol. 33, No. 2, 2001, pp. 240-247. doi:10.1086/321819
[5]	R. Webber, et al., “Liver-Related Deaths in Persons Infected with the Human Immunodeficiency Virus,” Formerly Archives of Internal Medicine, Vol. 166, No. 15, 2006, pp. 1632-1641. doi:10.1001/ archinte.166.15. 1632
[6]	J. G. McHutchison and M. W. Fried, “Current Therapy for Hepatitis C: Pegylated Interferon and Ribavirin,” Clinics in Liver Disease, Vol. 7, No. 1, 2003, pp. 149-161. doi:10.1016/S1089-3261(02) 00077-6
[7]	K.-H. Lin, et al., “Factors Linked to Severe Thrombocytopenia During Antiviral Therapy in Patients with Chronic Hepatitis C and Pretreatment Low Platelet Counts,” BMC Gastroenterology, Vol. 12, No. 7, 2012, pp. 1-8. doi:10.1186/1471-230X-12-7
[8]	A. Sarpatwari, et al., “Thromboembolic Events among Adult Patients with Primary Immune Thrombocytopenia in the United Kingdom General Practice Research Database,” Haematologica, Vol. 95 No. 7, 2010, pp. 1167-1175. doi:10.3324/haematol.2009.018390
[9]	E. Y. Chiao, et al., “Risk of Immune Thrombocytopenic Purpura and Autoimmune Hemolytic Anemia among 120 908 US Veterans with Hepatitis C Virus Infection,” Formerly Archives of Internal Medicine, Vol. 169, No. 4, 2009, pp. 357-363. doi:10.1001/archinternmed.2008.576
[10]	S. Panzer and E. Seel, “Is There an Increased Frequency of Autoimmune Thrombocytopenia in Hepatitis C Infection? A Review,” Wiener Medizinische Wochenschrift, Vol. 153, No. 19-20, 2003, pp. 417-420. doi:10.1007/s10354-003-0028-x
[11]	S. K. Rajan, B. M. Espina and H. A. Liebman, “Hepatitis C Virus-Related Thrombocytopenia: Clinical and Laboratory Characteristics Compared with Chronic I-mmune Thrombocytopenic Purpura,” British Journal of Haematology, Vol. 129, No. 6, 2005, pp. 818-824. doi:10.1111/j.1365-2141.2005.05542.x
[12]	P. S. Sullivan, et al., “Surveillance for Thrombocytopenia in Persons Infected with HIV: Results from the Multistate Adult and Adolescent Spectrum of Disease Project,” Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 14, No. 4, 1997, pp. 374-379. doi:10.1097/ 00042560-199704010- 00011
[13]	A. Scaradavou, “HIV-Related Thrombocytopenia,” Blood Reviews, Vol. 16, No. 1, 2002, pp. 73-76. doi:10.1054/ blre.2001.0188
[14]	L. Li, D.-K. Han and J. Lu, “Interferon-Alpha Induced Severe Thrombocytopenia: A Case Report and Review of the Literature,” World Journal of Gastroenterology, Vol. 16, No. 11, 2010, pp. 1414-1417. doi:10.3748/wjg.v16.i11.1414
[15]	N. Afdhal, et al., “Thrombocytopenia Associated with Chronic Liver Disease,” Journal of Hepatology, Vol. 48, No. 6, 2008, pp. 1000-1007. doi:10.1016/j.jhep.2008.03.009
[16]	M. M. Kitahata, et al., “Cohort Profile: The Centers for AIDS Research Network of Integrated Clinical Systems,” International Journal of Epidemiology, Vol. 37, No. 5, 2008, pp. 948-955. doi:10.1093/ije/ dym231
[17]	N. I. H. This, “National Institutes of Health Consensus Development Conference Statement: Management of Hepatitis C: 2002—June 10-12, 2002,” Hepatology, Vol. 36, No. 5B, 2002, pp. s3-s20. doi:10.1053/jhep.2002.37117
[18]	AIDSinfo, “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents,” 2011. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf.
[19]	P. Hui, et al., “The Frequency and Clinical Significance of Thrombocytopenia Complicating Critical Illness: A Systematic Review,” Chest, Vol. 139, No. 2, 2011, pp. 271-278. doi:10.1378/chest.10-2243
[20]	K. S. Louie, et al., “Prevalence of Thrombocytopenia among Patients with Chronic Hepatitis C: A Systematic Review,” Journal of Viral Hepatitis, Vol. 18, No. 1, 2011, pp. 1-7. doi:10.1111/j.1365-2893.2010.01366.x
[21]	A. K. Singal and B. S. Anand, “Management of Hepatitis C Virus Infection in HIV/HCV Co-Infected Patients: Clinical Review,” World Journal of Gastroenterology, Vol. 15, No. 30, 2009, pp. 3713-3824. doi:10.3748/wjg.15.3713
[22]	A. Pohl, et al., “Serum Aminotransferase Levels and Platelet Counts as Predictors of Degree of Fibrosis in Chronic Hepatitis C Virus Infection,” The American Journal of Gastroenterology, Vol. 96, No. 11, 2001, pp. 3142-3146. doi:10.1111/j.1572-0241.2001.05268.x
[23]	R. Testa, et al., “Noninvasive Ratio Indexes to Evaluate Fibrosis Staging in Chronic Hepatitis C: Role of Platelet Count/Spleen Diameter Ratio Index,” Journal of Internal Medicine, Vol. 260, No. 2, 2006, pp. 142-150. doi:10.1111/j.1365-2796.2006.01673.x
[24]	M. Osada, et al., “Causes of Thrombocytopenia in Chronic Hepatitis C Viral Infection,” Clinical and Appl ied Thrombosis Hemostasis, Vol. 18, No. 3, 2012, pp. 272-280. doi:10.1177/1076029611429124
[25]	A. A. M. Shaheen and R. P. Myers, “Diagnostic Accuracy of the Aspartate Aminotransferase-To-Platelet Ratio Index for the Prediction of Hepatitis C-Related Fibrosis: A Systematic Review,” Hepatology, Vol. 46, No. 3, 2007, pp. 912-921. doi:10.1002/hep.21835
[26]	H.-H. Thein, et al., “Estimation of Stage-Specific Fibrosis Progression Rates in Chronic Hepatitis C Virus Infection: A Meta-Analysis and Meta-Regression,” Hepatology, Vol. 48, No. 2, 2008, pp. 418-431. doi:10.1002/hep.22375
[27]	C. S. Graham, et al., “Influence of Human Immunodeficiency Virus Infection on the Course of Hepatitis C Virus Infection: A Meta-Analysis,” Clinical Infectious Diseases, Vol. 33, No. 4, 2001, pp. 562-569. doi:10.1086/321909
[28]	P. J. Ballem, et al., “Kinetic Studies of the Mechanism of Thrombocytopenia in Patients with Human Immunodeficiency Virus Infection,” The New England Journal of Medicine, Vol. 327, No. 25, 1992, pp. 1779-1784. doi:10.1056/NEJM199212173272503
[29]	The American Society of Hematology ITP Practice Guideline Panel, “Diagnosis and Treatment of Idiopathic Thrombocytopenic Purpura: Recommendations of the American Society of Hematology,” Annals Internal Medicine, Vol. 126, No. 4, 1997, pp. 319-326.
[30]	M. W. Fried, “Side Effects of Therapy of Hepatitis C and Their Management,” Hepatology, Vol. 36, No. 5B, 2002, pp. S237-S244. doi:10.1053/jhep.2002.36810
[31]	T. L. Kauf, et al., “Trends in the Prevalence of Thrombocytopenia among Individuals Infected with Hepatitis C Virus in the United States, 1999-2008,” BMC Research Notes, Vol. 5, No. 1, 2012, p. 142. doi:10.1186/1756-0500-5-142
[32]	G. Cheng, et al., “Eltrombopag for Management of Chronic Immune Thrombocytopenia (RAISE): A 6-Month, Randomised, Phase 3 Study,” The Lancet, Vol. 377, No. 9763, 2011, pp. 393-402. doi:10.1016/S0140-6736(10)60959-2
[33]	C. Neunert, et al., “The American Society of Hematology 2011 Evidence-Based Practice Guideline for Immune Thrombocytopenia,” Blood, Vol. 117, No. 16, 2011, pp. 4190-4207. doi:10.1182/blood-2010-08-302984