Epidemiology of HIV/HBV Coinfection in a U.S. Military Cohort

		SUMMARY: A study of nearly 3000 HIV positive patients treated at U.S. military health facilities found that 39% had evidence of hepatitis B virus (HBV) infection, and 11% had chronic hepatitis B, researchers reported in the February 1, 2010 issue of Clinical Infectious Diseases. HBV prevalence and incidence both declined significantly over time, though incidence stabilized around 2000. People with higher CD4 cell counts and those using HBV-active antiretroviral drugs had a lower likelihood of HBV infection after becoming HIV positive.

By Liz Highleyman

Helen Chun and colleagues with the Infectious Disease Clinical Research Program looked at the epidemiologic trends of HBV infection in HIV positive patients over the course of 20 years.

Because HIV and HBV have overlapping transmission routes, many people are infected with both viruses. Rates of hepatitis B in the population as a whole have fallen dramatically since the advent of routine childhood HBV vaccination, but trends among people with HIV have not been well studied.

A majority of HIV negative people infected with HBV as adults spontaneously clear the virus without treatment, but 5%-10% develop chronic infection lasting more that 6 months. But studies show that HIV positive people are more likely to develop chronic infection.

As people with HIV live longer due to effective combination antiretroviral therapy (ART), liver disease -- often associated with chronic hepatitis B or C coinfection -- accounts for an increasing proportion of morbidity and mortality. Fortunately, some of the ART drugs used to treat HIV are also active against HBV, namely lamivudine (3TC; Epivir), emtricitabine (Emtriva), and tenofovir (Viread, also in the Truvada and Atripla coformulations).

The study investigators examined prevalence and risk factors for HBV infection overall, at the time of HIV infection, and after HIV infection among 2769 participants in U.S. Military HIV Natural History Study, a prospective observational cohort of active duty service members and their dependents; participants continued to be followed after completing military service.

The researchers performed annual cross-sectional analyses of HBV prevalence (total cases) and incidence (new cases). Participants received a median of 4 HBV screenings. Risk factors for HBV infection at the time of HIV diagnosis and after HIV diagnosis were evaluated.

Results

	Of the 2769 participants evaluated, 1078 (39%) had HBV infection, of whom 117 (11%) had chronic hepatitis B.
	The prevalence of all HBV infection decreased significantly over time, from a peak of 49% in 1995 to 36% in 2008.
	The prevalence of all HBV infection existing at the time of HIV diagnosis also declined significantly, from 34% in 1989 to 9% in 2008.
	For chronic HBV infection, the prevalence fell from a peak of 7% in 1995 to an estimated 4% in 2008.
	By vaccination status, the prevalence of chronic HBV infection during the ART era was 7% among unvaccinated participants and 2% among vaccinated individuals.
	Among 1872 participants who were HBV negative at the time of HIV diagnosis, 181 (9.7%) became HBV infected during follow-up, of whom 37 (20.4%) developed chronic hepatitis B.
	The incidence of new HBV infections after HIV diagnosis decreased from 4.0 cases per 100 person-years before the advent of combination ART to 1.1 cases per 100 person-years during the ART era.
	Incidence then stabilized, however, and remained unchanged from 2000 through 2008, at a rate about 100 times higher than that of HIV negative service members and 500 times higher than that of the general U.S. population.
	More than 20% of HBV infections that occurred after HIV infection became chronic -- considerably higher than the expected rate among HIV negative people.
	In a multivariate analysis, higher risk of HBV infection at the time of HIV diagnosis was significantly associated with older age, male sex, and history of gonorrhea or syphilis,
	Risk of HBV infection after HIV diagnosis was associated with male sex, lower CD4 cell count and not using HBV-active ART, but not with receiving more than 1 HBV vaccine dose.
	Mortality declined dramatically after the advent of combination ART, with similar changes seen among HIV/HBV coinfected patients (29% to 4%) and those without HBV (27% vs 1%).

Based on these findings, the researchers wrote, "Although the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection after diagnosis of HIV infection raises concern that more effective prevention strategies may be needed to significantly reduce the prevalence of HBV infection in this patient population."

"This comprehensive examination of the epidemiology of HBV infection in a large cohort of HIV-infected individuals highlights the continued and significant burden of HBV infection in HIV-infected adults, with nearly 40% of patients with HIV infection also having coinfection with HBV," they elaborated in their discussion.

"Despite the gradual decrease in prevalence of chronic HBV infection over the past 2 decades, overall, 11% of patients with HBV infection had chronic HBV infection," the researchers continued. "Furthermore, HBV infections after diagnosis of HIV infection continue to occur, and although the number of such HBV infections has decreased in the HAART era, incidence rates have remained unchanged for the past 8 years, suggesting that additional efforts will be needed to further reduce the incidence rate of HBV coinfection."

"Effective prevention methods are needed and must overcome the effects of HIV-associated immune dysfunction on HBV transmission and vaccine effectiveness," they concluded. "The associations of HBV-active HAART use and higher CD4 cell count with decreased risk of incident HBV infection suggest additional benefits of HAART and provide further rationale for increased use of HBV-active HAART."

Naval Health Research Center and Naval Medical Center San Diego, San Diego, CA; University of Minnesota, Minneapolis, MN; Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences and National Naval Medical Center, Bethesda, MD: Walter Reed Army Medical Center, Washington, DC; Naval Medical Center Portsmouth, Portsmouth, VA; San Antonio Military Medical Center, Fort Sam Houston, TX.

1/29/10

Reference
HM Chun, AM Fieberg, K Huppler, and others. Epidemiology of Hepatitis B Virus Infection in a US Cohort of HIV-Infected Individuals during the Past 20 Years. Clinical Infectious Diseases 50: 426-436 (Abstract). February 1, 2010.