Hepatitis B co-infection doesn't affect response to HIV treatment

Co-infection with hepatitis B virus does not affect responses to HIV treatment, American investigators report in a study published in the online edition of AIDS. They also found no evidence that HIV/hepatitis B-infected individuals taking antiretroviral therapy had an increased risk of dying of an AIDS-defining illness. However, co-infected individuals had an increased risk of dying of illnesses not normally considered HIV-related, including both liver disease and cardiovascular illnesses.

Between 5 and 10% of HIV-positive individuals in countries like the US and UK have chronic hepatitis B infection. Much higher rates of co-infection exist in some resource-limited settings. The impact of hepatitis B co-infection on responses to HIV treatment in terms of viral suppression, CD4 cell recovery and HIV disease progression is unclear and research to date has yielded conflicting results.

Investigators from the US Multicenter AIDS Cohort Study (MACS) therefore designed a study involving 816 men with experience of long-term antiretroviral therapy.

These patients were divided into groups according to their hepatitis B infection status:

• Never infected (350 individuals).
• Infected but cleared the virus (357 individuals).
• Chronic hepatitis B infection (45 individuals).
• Isolated core infection (64 individuals).

The investigators then compared outcomes in these patients over a median of seven years of follow-up.

Outcomes included:

• AIDS-related death.
• Non-AIDS-related death.
• HIV viral load.
• CD4 cell count.

Overall, 87 patients died after starting potent HIV treatment, a mortality rate of 17 per 1000 person-years.

Despite the use of HIV treatment, AIDS-related causes were the most common cause of death, accounting for 43 deaths (8.4 per 1000 person-years).

AIDS-related deaths were most common in patients with chronic hepatitis B infection (17 per 1000 person-years), followed by individuals with isolated core infection (14 per 1000 person-years), and individuals with past hepatitis B infection (11 per 1000 person-years). HIV-related deaths were least common in individuals never infected with hepatitis B (3 per 1000 person-years).

Adjusting for factors that could independently affect prognosis, such as baseline CD4 cell count, number of study visits with an undetectable viral load, injecting drug use, and initiation of HIV therapy after 1996, showed that although individuals with chronic hepatitis B infection had a higher risk of HIV-related death compared to individuals never infected with hepatitis B, the difference was not statistically significant (p = 0.08).

There were a total of 30 non-HIV-related deaths. The rate of such deaths was highest in individuals with chronic hepatitis B infection (22 per 1000 person-years), followed by those isolated core infection (14 per 1000 person-years) and past infection with hepatitis B (6 per 1000 person-years). Deaths because of non-AIDS-related illnesses were least frequent in patients never infected with hepatitis B (2 per 1000 person-years).

After adjusting for potentially confounding factors, chronic hepatitis B infection (p = 0.04) remained associated with an increased risk of death from non-HIV-related illnesses, and isolated core was of borderline significance (p = 0.06).

Four of the six non-HIV-related deaths amongst hepatitis B-chronically infected individuals were liver-related. This rate of liver mortality (17 per 1000 person-years) was significantly higher than in any other group (p = 0.05)

There were five non-AIDS-related deaths amongst patients with isolated core hepatitis B infection. Four of these deaths were due to cardiovascular causes. One of these deaths was in an individual who was also infected with the hepatitis C virus, and another in an injecting drug user.

The investigators’ first set of statistical analysis showed that isolated core-infected individuals were less likely than other groups to achieve HIV suppression (p = 0.02). But after adjustment for potentially confounding factors, hepatitis B infection status was not shown to affect virological response to HIV therapy.

Nor did hepatitis B co-infection impact on changes in CD4 cell count after the initiation of HIV treatment. The only factors significantly affecting this outcome were baseline CD4 cell count (p = 0.01), and the proportion of study visits with an undetectable viral load (p

“This study demonstrates that hepatitis B virus status at HAART initiation does not affect the long-term ability of HIV-infected patients to respond to HAART in terms of HIV RNA suppression and immunological recovery,” conclude the investigators. However, they note that an increased risk of liver-related death existed for some chronically infected individuals, and suggest that research should be devoted to the development of anti-hepatitis B therapies that offer durable suppression of the virus.