Hepatitis B Virus Co-Infection: Yet Another Reason for Early Initiation of Treatment in HIV Infected Individuals

Yared Hailaye, Muluken Dessalegn, Solomon Gebre-Selassie

Addis Ababa Science and Technology University, Medicine and Health Science College, Addis Ababa, Ethiopia.
Department of Medical Microbiology, Medical Parasitology and Immunology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia..
Department of Medicine, School of Medicine, Debre Berhan University, Debre Berhan, Ethiopia.

DOI: 10.4236/wja.2013.34040                

Abstract

Background: Hepatitis B virus (HBV) co-infection with HIV is becoming a major challenge due to shared routes of transmission. The burden is apparent in regions with widespread use of antiretroviral treatment, which led to the enhanced emergence of liver-related diseases and mortality. Though there are conflicting results about the effect of chronic HBV infection on response to highly active antiretroviral therapy (HAART) (CD4⁺ cell count and HIV viral load, HIV RNA copies/ml), HAART is known to cause immune mediated HBV specific liver damage after it reconstitutes cell-mediated immunity. The relationship of different HAART regimes with immune recovery is an area of research interest. Objective: It is in order to determine the changes in immune recovery during HBV infection in the setting of HAART among HIV positive individuals attending care and treatment services. Methods: Two cohorts of co-infected patients were analyzed from data of one to seven months retrospectively. The first group (n = 380) was antiretroviral drug naive and the second cohort (n = 380) was on HAART for the entire period. The study was conducted in one referral hospital and six health centers. Data were gathered from 760 patients using their intake form, their follow-up form and their medical records supplemented by data from a structured questionnaire. HBV infection was determined by using HBsAg rapid and confirmatory tests and CD4 cells were enumerated by using laboratory registers and patient cards. Bivariate and multivariate logistic regressions were done by using SPSS Version 18 and Epi info Version 3.5. Results: Poor immune recovery due to HBV infection was improved after initiation of HAART. Before the initiation of HAART, the mean CD4 cell count of HBV infected individuals was lower than that of non-HBV infected ones, 234/mm³ and 384/mm³, respectively (p < 0.05). Individuals co-infected with HBV had experienced delayed recovery of immune cells (CD4 cell count). However, after, on average, more than two years of therapy, the association is reversed. In addition to HBV infection, CD4 cell count of patients on chronic HIV care/pre-ART was decreased by older age, living in rural areas and previous opportunistic infections. Conclusion: HBV infection has different outcomes between pre-ART and ART-initiated individuals. In the former cohort, HBV infection causes significant delays in immune recovery which is reversed after initiation of anti-HIV treatment. HBV co-infection has a significant and immediate negative effect on CD4 cell counts and immune recovery before HAART but such effects slowly subside after initiation of the treatment. As a result, HBV infection is another issue to consider for swift initiating of HAART for HIV infected individuals in long-term care.

 

Keywords

HAART; CD4 Cell Count; HBsAg; HBV/HIV Co-Infection; Immune Recovery

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	WHO, “Antiretroviral Therapy for HIV Infection in Adults and Adolescents,” Recommendations for a Public Health Approach, WHO, 2006, p. 26.
[2]	V. Levy and M. Robert, “Antiretroviral Therapy for Hepatitis B Virus-HIV Co-Infected Patients: Promises and Pitfalls,” Clinical Infectious Diseases, Vol. 43, No. 10, 2006, pp. 904-910. http://dx.doi.org/10.1086/507532
[3]	H. L. Omland, et al., “Impact of Hepatitis B Virus CoInfection on Response to Highly Active Antiretroviral Treatment and Outcome in HIV-Infected Individuals: A Nationwide Cohort Study,” British HIV Association HIV Medicine, Vol. 9, No. 5, 2008, pp. 300-306. http://dx.doi.org/10.1111/j.1468-1293.2008.00564.x
[4]	K. Lacombe, et al., “HIV/Hepatitis B Virus Co-Infection: Current Challenges and New Strategies,” Journal of Antimicrobial Chemotherapy, Vol. 65, No. 1, 2010, pp. 10-17. http://dx.doi.org/10.1093/jac/dkp414
[5]	S. Kenneth, P. Marion and K. Margaret, “HIV and Liver Disease Forum: Conference Proceedings,” Hepatology, Vol. 45, No. 6, 2007, pp. 1566-1577. http://dx.doi.org/10.1002/hep.21722
[6]	C. J. Hoffmann and C. L. Thio, “Clinical Implications of HIV and Hepatitis B Co-Infection in Asia and Africa,” The Lancet Infectious Diseases, Vol. 7, No. 6, 2007, pp. 402-409. http://dx.doi.org/10.1016/S1473-3099(07)70135-4
[7]	M. G. Peters, “Diagnosis and Management of Hepatitis B Virus and HIV Coinfection,” Topics in HIV Medicine, Vol. 15, No. 5, 2007, pp. 163-166.
[8]	M. Gomez-Gonzalo, M. Carretero and J. Rullas, “The Hepatitis B Virus X Protein Induces HIV-1 Replication and Transcription in Synergy with T-Cell Activation Signals,” The Journal of Biological Chemistry, Vol. 38, 1976, pp. 35435-35443.
[9]	V. Soriano, et al., “Care of HIV Patients with Chronic Hepatitis B: Updated Recommendations from the HIVHepatitis B Virus International Panel,” AIDS, Vol. 22, No. 12, 2008, pp. 1399-1410. http://dx.doi.org/10.1097/QAD.0b013e3282f8b46f
[10]	V. DiMartino, “Influence of HIV Infection on the Response to Interferon Therapy and the Long Term Outcome of Chronic Hepatitis B,” Gastroenterology, Vol. 123, No. 6, 2002, pp. 1812-1822. http://dx.doi.org/10.1053/gast.2002.37061
[11]	E. Ameeta and T. Wong, “HIV and Hepatitis B Co-Infection: Background Document,” WHO, 2009.
[12]	R. K. Sterling, “Hepatitis B Virus in the Setting of HIV Infection: A Clinical Challenge. Medical Writers’ Circle,” 2003. http://www.hcvadvocate.org/hcsp/board.asp
[13]	A. DeLuca, R. Bugarini and A. C. Lepri, “Co-Infection with Hepatitis Viruses and Outcome of Initial Antiretroviral Regimens in Previously Naive HIV-Infected Subjects,” Archives of Internal Medicine, Vol. 162, No. 18, 2002, pp. 2125-2132. http://dx.doi.org/10.1001/archinte.162.18.2125
[14]	J. Idoko, S. Meloni and M. Muazu, “Hepatitis B virus CoInfection Impacts Baseline HIV Parameters and HAARTRelated Hepatotoxicity Risk in an HIV-Infected Nigerian Cohort,” 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, 25-28 February 2007.
[15]	M. Puoti, et al., “Hepatitis B Virus Co-Infection in Human Immunodeficiency Virus-Infected Subjects,” AIDS Reviews, Vol. 4, No. 1, 2002, pp. 27-35.
[16]	C. L. Thio, et al., “HIV-1, Hepatitis B Virus, and Risk of Liver Related Mortality in the Multicenter Cohort Study (MACS),” Lancet, Vol. 360, No. 9349, 2002, pp. 1921-1926. http://dx.doi.org/10.1016/S0140-6736(02)11913-1
[17]	T. Wilkin, “What Causes Poor CD4-Cell Recovery in the Setting of Suppressive Antiretroviral Therapy?” Journal Watch HIV/AIDS Clinical Care, 2010. http://aids-clinical-care.jwatch.org
[18]	J. J. Chang, et al., “Reduced Hepatitis B Virus (HBV)Specific CD4_ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy,” Journal of Virology, Vol. 79, No. 5, 2005, pp. 3038-3051. http://dx.doi.org/10.1128/JVI.79.5.3038-3051.2005
[19]	M. Crane, S. Sirivichayakul and J. J. Chang, “No Increase in Hepatitis B Virus (HBV)-Specific CD8-T Cells in Patients with HIV-1-HBV Co-Infections Following HBVActive HAART,” Journal of Virology, Vol. 84, No. 6, 2010, pp. 2657-2665. http://dx.doi.org/10.1128/JVI.02124-09
[20]	M. Mascolini, “Older Age, Lower CD4 Nadir, NNRTI Use Predict Slow CD4 Recovery in Athena,” 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, 16-19 February 2010.
[21]	S. Mauss, et al., “Hepatology: A Clinical Textbook,” Flying Publisher, Germany, 2009. www.HepatologyTextbook.com
[22]	Y. Benhamou, M. Bochet and V. Thibault, “Long-Term Incidence of Hepatitis B Virus Resistance to Lamivudine in Human Immunodeficiency Virus-Infected Patients,” Hepatology, Vol. 30, No. 5, 1999, pp. 1302-1306. http://dx.doi.org/10.1002/hep.510300525