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.