AIDS 2016: Ongoing Hepatitis B Virus Replication Raises Mortality for People with HIV


People with HIV and hepatitis B virus (HBV) coinfection 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 coinfection session at the 21st International AIDS Conference (AIDS 2016) last month in Durban.

Coinfections 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 from the French National Agency for AIDS Research (ANRS) looked at outcomes among people coinfected 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 9 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 ongoing active viral replication.

Out of 2052 participants analyzed, 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.


"There is a 2.5-times higher mortality in patients with HBV DNA greater than 7000 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 coinfected patients with high HBV replication."

During the discussion, session moderator Jürgen Rockstroh 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 AASLD and EASL hepatitis B guidelines as the threshold for antiviral treatment, as higher levels are associated with a greater risk of liver cancer and other complications.



MG Kouamé, R Moh, A Boyd, et al. Higher mortality in HIV-HBV co-infected persons with elevated HBV replication in the Temprano Trial. 21st International AIDS Conference. Durban, July 18-22, 2016.Abstract WEAB0303.