Co-infection with hepatitis B worsens HIV-related outcomes

Co-infection with hepatitis B virus increases the risk of AIDS or death for patients newly diagnosed with HIV, investigators from the US military report in the online edition of the Journal of Infectious Diseases.

Individuals with chronic hepatitis B infection were twice as likely to progress to AIDS/death compared to patients who were only infected with HIV.

“With compelling data confirming the risk for persons with co-infection, it is imperative that we commit to implement…additional steps to combat hepatitis B now,” write the authors of an accompanying editorial.

HIV and hepatitis B share modes of transmission. These include sexual exposure, injecting drug use and mother-to-child transmission. Therefore a significant proportion of HIV-positive patients are co-infected with HIV.

Infection with HIV can accelerate the course of hepatitis B disease.

“HIV co-infection is known to influence the natural history and course of hepatitis B by impairing the quantity and quality of the innate and adaptive immune response,” explain the authors.

There is no cure for hepatitis B, but a number of antiretroviral drugs are active against both HIV and hepatitis B and can thus help prevent liver damage and disease progression.

Studies exploring the impact of hepatitis B on HIV-related outcomes have yielded conflicting results. However, these studies were limited by their inability to control for a number of factors, including duration of infection with HIV.

In order to overcome this limitation, investigators from the US military designed a retrospective study, involving patients with an approximate date of HIV-seroconversion who were categorised according to their hepatitis B infection status. A series of analysis were then conducted to assess the impact of co-infection on the risk of progression to AIDS and death.

Patients diagnosed with HIV since 1986 were included in the study. All had been repeatedly screened for the infection and it was possible to estimate the date of their seroconversion within three years.

Their routine care involved testing for hepatitis B. This screening showed that 74% had never been infected with the virus; 20% had resolved hepatitis B infection; 4% had isolated hepatitis B core antigen (HBcAb); and 3% had chronic hepatitis B infection.  

Importantly, 48% of patients were diagnosed with HIV before the advent of effective HIV therapy in 1996.

The investigators had 16, 946 person years of follow-up available for analysis. During this time, 305 patients developed AIDS and 164 died.

Initial analysis showed that hepatitis B infection status was significantly associated with these outcomes.

Compared to individuals with no hepatitis B infection, patients with chronic hepatitis B were over twice as likely to develop AIDS or die (RR = 2.23; 95% CI, 1.51-3.28). The risk of these outcomes was also significantly increased for patients with isolated HBcAb (RR = 1.54; 95% CI, 1.02-2.34), and for those with resolved hepatitis B infection (RR = 1.35; 95% CI, 1.09-1.66).

Subsequent analysis that controlled for potential confounding factors, such as year or diagnosis and use of potent HIV therapy showed that showed that chronic hepatitis B infection remained associated with a significant risk of AIDS or death (HR = 1.80; 95% CI, 1.20-2.69). There was also a non-significant trend suggesting that resolved hepatitis B infection (HR = 1.17; 95% CI, 0.94-1.46) and isolated HBcAb (HR = 1.14; 95% CI, 0.75-1.75) were also associated with AIDS or death.

“We found that hepatitis B virus infection has a significant impact on HIV outcomes,” comment the investigators. “We also found an increased risk of AIDS or death in the HAART [highly active antiretroviral therapy] era, despite the fact that the majority of participants received an hepatitis B-active drug as part of their regimen.”

Only a fifth of patients had been vaccinated against hepatitis B, leading the investigators to suggest: “Our findings underscore the need to prevent hepatitis B in those with HIV and also in cohorts of HIV-negative individuals with risk factors for HIV acquisition.”

However, the study had a number of limitations. Most notably, it did not differentiate the causes of death, and many of the deaths in co-infected patients could have been due to factors other than hepatitis B.

Nevertheless, the authors of an accompanying editorial believe the research “adds to the weight of evidence that co-infection is deleterious by demonstrating that in a well-characterised cohort, it doubles the risk of AIDS-defining illness and death.”

They believe this underscores the importance of vaccinating individuals with or at risk of HIV against HIV and the inclusion of drugs that work against both infections in the antiretroviral therapy of co-infected patients.