Ongoing hepatitis B virus replication associated with higher mortality for people with HIV

Menan Gérard Kouamé presenting at AIDS 2016. Photo by Liz Highleyman, hivandhepatitis.com

People with HIV and hepatitis B virus (HBV) co-infection have more than double the risk of death if they have ongoing 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.

Glossary

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

deoxyribonucleic acid (DNA)

The material in the nucleus of a cell where genetic information is stored.

replication

The process of viral multiplication or reproduction. Viruses cannot replicate without the machinery and metabolism of cells (human cells, in the case of HIV), which is why viruses infect cells.

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

Menan Gérard Kouamé of the French National Agency for AIDS Research (ANRS) looked at outcomes among people with HIV and HBV co-infection 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 (WHO) 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 ongoing active viral replication.

Out of 2052 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 1605 HBsAg-negative people in long-term follow-up until the last participant reached 30 months.

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 7000 copies/ml.

HBsAg-negative participants and HBsAg-positive participants with HBV DNA < 7000 copies/ml both had very high survival, 96% at 78 months. Among HBsAg-positive people with HBV DNA > 7000 copies/ml, however, survival fell to 78%.

Comparing 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 categorised by HBV DNA level, HBsAg-positive people with < 7000 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 ratio 2.51).

"There 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 replication."

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 2000 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.

References

Kouamé MG et al. Higher mortality in HIV-HBV co-infected persons with elevated HBV replication in the Temprano Trial. 21st International AIDS Conference, Durban, abstract WEAB0303, 2016.

View the abstract on the conference website.

Download the presentation slides from the conference website.

Watch the webcast of this presentation on YouTube.

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