Meta-analysis Shows Concurrent Hepatitis B Increases All-cause Mortality in People with HIV

HIV positive people coinfected with hepatitis B virus (HBV) have a higher rate of all-cause death than people with HIV alone, according to a report in the June 15, 2009 issue of Clinical Infectious Diseases. These results, the study authors stated, suggest that HIV-HBV coinfected individuals may especially benefit from efforts to minimize liver damage.

Due to overlapping routes of transmission, some individuals with HIV also have chronic HBV infection. Over time, chronic hepatitis B can lead to advanced liver cirrhosis and liver cancer, and there is evidence to suggest that this may happen faster in HIV positive people, especially those with low CD4 cell counts.

G.K. Nikolopoulos from the University of Athens and colleagues conducted a retrospective cohort study to examine the effects of concurrent HBV infection on the natural history of HIV/AIDS progression and overall mortality. They also performed a meta-analysis -- the first to look at HIV-HBV coinfection -- adding their data to those from previous studies.

The investigators measured hepatitis B surface antigen (HBsAg) in serum samples collected from 1729 patients in Greece diagnosed with HIV between 1984 and 2003. For the meta-analysis, they identified eligible articles from the medical literature, abstracted relevant data, and calculated pooled estimates of the effect of HBV on HIV disease. This analysis included data from a total of 12,382 participants enrolled in 11 studies.


  • The prevalence of chronic HBV infection, defined as documented HBsAg seropositivity lasting for at least 6 months, was about 6%.
  • In the primary study, a multivariate analysis revealed no significant impact of HIV-HBV coinfection on progression to AIDS, effectiveness of antiretroviral therapy, or all-cause mortality.
  • The meta-analysis, however, revealed that HIV-HBV coinfection had a significant effect on overall mortality (pooled effect estimate 1.36).
  • HIV-HBV coinfected individuals had an increased rate of death in studies conducted both before and after the advent of effective combination antiretroviral therapy (pooled effect estimates 1.60 and 1.28, respectively).
  • Coinfection did not, however, have a significant effect on progression to AIDS.

Based on these findings, the study authors concluded, "HIV-HBV coinfection seems to affect all-cause mortality, and strategies to reduce liver damage in patients coinfected with HIV and HBV are justified."

In an accompanying editorial, Mamta Jain from the University of Texas Southwestern Medical Center noted that this analysis did not separate out liver-related death, so it is unclear how many patients died of causes directly related to HBV infection. It is also possible that HIV-HBV coinfection is a marker for other factors -- such as injection drug use -- linked to an elevated risk of death due to other types of causes.

Every HIV treatment provider must accurately diagnose hepatitis B, document HBV viral load prior to starting antiretroviral therapy, monitor HBV DNA levels to ensure that viral suppression is achieved (a majority of adults exposed to HBV clear the virus without treatment, though this is less common among HIV positive people), screen for hepatocellular carcinoma (liver cancer), and advise patients about the harmful effects of alcohol on the liver, he advised.

In light of these findings, Jain concluded, "aggressive treatment of hepatitis B is warranted" for people who do not spontaneously clear the virus. HIV-HBV coinfected patients who need hepatitis B treatment -- regardless of CD4 count -- should receive a full combination antiretroviral regimen including drugs with dual activity against both viruses (lamivudine [3TC; Epivir], emtricitabine [Emtriva], and tenofovir [Viread]), as recommended in the latest DHHS HIV treatment guidelines.



GK Nikolopoulos, D Paraskevis, E Hatzitheodorou, and others. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clinical Infectious Diseases 48(12): 1763-1771. June 15, 2009.

MK Jain. Mortality in patients coinfected with hepatitis B virus and HIV: could antiretroviral therapy make a difference? (Editorial). Clinical Infectious Diseases 48(12): 1772-1774. June 15, 2009.