Steven M. Fine, MD, PhD

Disclosures

August 20, 2014

In This Article

HIV/HBV Coinfection: Expert Commentary

Although hepatitis B is a vaccine-preventable infection, it remains common, with an estimated 1 to 1.25 million people chronically infected with hepatitis B virus (HBV) in the United States. These carriers are at risk for progression to end-stage liver disease, hepatocellular carcinoma, and transmission of HBV to others.

Because HIV and HBV have similar modes of transmission (blood and sexual transmission) and fewer patients with HIV clear HBV infection, HIV-infected persons have a higher prevalence of chronic HBV infection than the general population. Although these rates vary depending on the population studied, estimates in some populations are as high as 5%-10%.1-3

Coinfection with HIV and HBV presents both a challenge and an opportunity for clinicians, because coinfected patients may progress to end-stage liver disease more rapidly than HBV-monoinfected patients, and they have higher rates of hepatocellular carcinoma.4 Medications active against both HIV and HBV allow for simplified regimens; however some HBV medications should not be used alone in HIV patients because they are active against HIV as well as HBV and may thus select for resistant strains of HIV if not used as part of a fully suppressive HIV regimen.5 Limited data from randomized trials are available to guide the treatment of HIV/HBV-coinfected patients, so the accompanying guideline tries to balance what is known with what seems most likely to be beneficial in terms of treatment of these patients.

The guideline discusses in detail the initial evaluation of the HIV-infected patient, including vaccination and other methods to prevent acquisition or transmission of hepatitis B. Important updates to the guideline in the area of vaccination include consideration of an accelerated course of vaccination for patients with CD4 counts > 500 cells/mm3 and using a series of either 3 or 4 double doses of HBV vaccine.6-9

Prevention of other liver-related diseases, such as hepatitis A and C, and damage caused by alcohol use is also discussed.

Perhaps the most important update to the HBV guideline results from the availability of potent medications active against both HIV and HBV, such as tenofovir, lamivudine, and emtricitabine, coupled with increasing evidence that it is beneficial to treat HIV at any stage of infection, even if the CD4 cell count remains high. Thus, the guidelines no longer recommend treating patients for HIV but not HBV, nor treating for HBV but not HIV. In the vast majority of HIV/HBV-coinfected patients, treatment that is active against both viruses should be initiated. Most regimens will therefore contain tenofovir with either emtricitabine or lamivudine.

Clinicians should avoid using HBV medications such as entecavir or adefovir in patients who are not fully HIV-suppressed, because they have some anti-HIV activity and can select for resistant strains of HIV virus. Caution needs to be maintained when changing or interrupting antiretroviral regimens that are also active against HBV because sudden withdrawal of HBV treatment can result in transaminase flares and liver damage.

One of the most difficult aspects of caring for HIV/HBV-coinfected patients who are on potent antiretroviral and anti-HBV therapy is determining who is at high risk of developing hepatocellular carcinoma (HCC) and how best to screen for it. The benefits of early detection of HCC are substantial, and a 5-year survival rate over 70% can be achieved at experienced centers. The risks of surveillance -- including cumulative doses of radiation if CT is used, high costs, and false-positive findings -- must be weighed against the benefits.

Currently, this guideline parallels the HCC screening guidelines from the European Association for the Study of the Liver and American Association for the Study of Liver Diseases for HBV-monoinfected patients.10,11 Although the risk of developing HCC is lower in those with chronic HBV who are on treatment, the magnitude of risk reduction is not known and screening is still recommended for most patients, generally with triple-phase CT scan or ultrasonography every 6-12 months. Patients with known risk factors for HCC as outlined in table 5 of the guideline should especially undergo surveillance for HCC. Screening for HCC with periodic alpha-fetoprotein (AFP) measurements is no longer recommended.

Although the best approaches for preventing and treating hepatitis B infection in HIV patients are still being studied, this guideline attempts to summarize what we feel are the best practices based on information available today, and highlights the importance of treating both HIV and HBV infections together as well as carefully considering screening for HCC.

References

  1. Kellerman SE, Hanson DL, McNaghten AD, Fleming PL. Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects. J Infect Dis. 2003;188:571-577. Abstract

  2. Lincoln D, Petoumenos K, Dore GJ; Australian HIV Observational Database. HIV/HBV and HIV/HCV coinfection, and outcomes following highly active antiretroviral therapy. HIV Med. 2003;4:241-249. Abstract

  3. Spradling PR, Richardson JT, Buchacz K, Moorman AC, Brooks JT; HIV Outpatient Study (HOPS) Investigators. Prevalence of chronic hepatitis B virus infection among patients in the HIV Outpatient Study, 1996-2007. J Viral Hepat. 2010;17:879-886. Abstract

  4. Ioannou GN, Bryson CL, Weiss NS, Miller R, Scott JD, Boyko EJ. The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency infection. Hepatology. 2013;57:249-257. Abstract

  5. Alberti A, Clumeck N, Collins S, et al; ECC Jury. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol. 2005;42:615-624. Abstract

  6. Fonseca MO, Pang LW, de Paula Cavalheiro N, Barone AA, Heloisa Lopes M. Randomized trial of recombinant hepatitis B vaccine in HIV-infected adult patients comparing a standard dose to a double dose. Vaccine. 2005;23:2902-2908. Abstract

  7. de Vries-Sluijs TE, Hansen BE, van Doornum GJ, et al. A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients. J Infect Dis. 2008;197:292-294. Abstract

  8. Psevdos G, Kim JH, Groce V, Sharp V. Efficacy of double-dose hepatitis B rescue vaccination in HIV-infected patients. AIDS Patient Care STDS. 2010;24:403-407. Abstract

  9. de Vries-Sluijs TE, Hansen BE, van Doornum GJ, et al. A randomized controlled study of accelerated versus standard hepatitis B vaccination in HIV-positive patients. J Infect Dis. 2011;203:984-991. Abstract

  10. Bruix J, Sherman S; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020-1022. www.aasld.org/practiceguidelines/Documents/HCCUpdate2010.pdf Accessed March 17, 2014.

  11. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: Management of hepatocellular carcinoma. J Hepatol. 2012;56:908-943. Abstract

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