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Ongoing hepatitis B virus replication associated with higher mortality for people with HIV
Liz Highleyman, 2016-08-16 09:30:00
with HIV and hepatitis B virus (HBV) co-infection have more than double the
risk of death if they have on-going high-level HBV replication, indicating a
need for prompt treatment, according to an analysis from the Temprano trial
presented at an HIV and viral hepatitis co-infection session at the 21st International AIDS Conference (AIDS 2016) last month in Durban, South Africa.
Co-infections including hepatitis B
and C and tuberculosis (TB) represent major causes of illness and death for
people living with HIV. Experts estimate that around 10% of HIV-positive adults
in West African countries also have HBV.
Over years or decades hepatitis B can
lead to serious outcomes including cirrhosis and liver cancer, and liver
disease is a leading contributor to mortality among people with HIV. Yet the
impact of viral hepatitis on the HIV epidemic in resource-limited countries is
not well understood.
Menan Gérard Kouamé of the French National Agency for AIDS Research (ANRS) looked at
outcomes among people co-infected with HIV and HBV in the Temprano trial.
In brief, Temprano assessed the benefits and risks of
early antiretroviral therapy (ART) and isoniazid prophylaxis therapy to prevent
active TB at nine clinics in Abidjan, Ivory Coast. Last year, investigators reported that starting HIV treatment with a CD4 count above 500
cells/mm3 reduced the risk of serious illness and death
compared to starting at lower CD4 thresholds set forth in older World Health
Organization guidelines. (WHO now recommends prompt treatment for everyone diagnosed with HIV.)
Temprano participants were tested for
hepatitis B surface antigen (HBsAg), which indicates HBV infection, and
those who tested positive received hepatitis B 'e' antigen (HBeAg) tests and
HBV DNA viral load tests to determine if there was on-going active viral
Out of 2,052 participants analysed, 190 (9%) tested positive for HBsAg,
of whom 12 died and 23 were lost to follow-up. Among the HBsAg-negative
participants, 74 died and 183 were lost. Kouamé presented findings for 155 HBsAg-positive and 1,605
HBsAg-negative people in long-term follow-up until the last participant reached
The HBsAg-positive and HBsAg-negative
groups were generally similar; 29% and 20%, respectively, were women and the
median age was 35 years. The median CD4 count was approximately 460 cells/mm3,
HIV viral load was around 50,000 copies/ml and half in both groups started
early ART and received isoniazid prophylaxis. All first-line ART
regimens contained tenofovir/emtricitabine (the drugs in Truvada), which are active against HBV as well as HIV.
In the HBsAg-positive group, 14% were
also HBeAg-positive and the median HBV DNA level was 523 copies/ml, with 27%
being above a cut-off of 7,000 copies/ml.
HBsAg-negative participants and HBsAg-positive participants with HBV DNA
<7,000 copies/ml both had very high survival, 96% at 78 months. Among
HBsAg-positive people with HBV DNA >7,000 copies/ml, however, survival fell
the HBsAg-negative and HBsAg-positive groups overall,
mortality rates were 0.87 and 1.38 deaths per 100 person-years (PY),
respectively (adjusted hazard ratio 1.48).
When categorized by HBV DNA level, HBsAg-positive people with <7,000
copies/ml had the same mortality as HBsAg-negatives (0.87 per 100 PY). But mortality
for those with higher HBV DNA levels rose to 2.63 per 100 PY (adjusted hazard
is a 2.5-times higher mortality in patients with HBV DNA greater than 7,000
copies/ml enrolled in the Temprano trial," the investigators concluded,
recommending that, "early ART needs to be provided to all HIV
infected-patients and especially to co-infected patients with high HBV
During the discussion, session moderator Jürgen Rockstroh of the University of Bonn noted
that it would be interesting to see if the results were the same using a HBV
DNA cut-off of 2,000 copies/ml, which is specified in EASL and AASLD hepatitis B
guidelines as the threshold for antiviral treatment, as higher levels are
associated with a greater risk of liver cancer and other complications.