HIV-positive individuals coinfected with hepatitis B virus are just as likely to have a good immunological and virological response to HAART, according to data from the EuroSIDA cohort published in the April 8th issue of the journal AIDS.
The international team of investigators also found that 9% of patients in the cohort were coinfected with HIV and hepatitis B virus, that all-cause and liver-related mortality was significantly higher amongst coinfected patients, and that a strong immune response to HAART was associated with a significant reduction in the risk of death amongst coinfected patients. The investigators also argue that coinfected individuals should take a HAART regimen which includes drugs which are active against both HIV and hepatitis B virus.
Background and EuroSIDA
Earlier studies have provided conflicting data about the prevalence of hepatitis B virus amongst HIV-positive individuals and the impact of coinfection with hepatitis B virus on the HIV disease progression.
Investigators from the EuroSIDA Cohort Study therefore determined to establish the prevalence of hepatitis B surface antigen (HBsAg) in their patients, as well as the level of all-cause and liver-related mortality in patient with and without hepatitis B virus. They also wished to establish if coinfected patients had a different response to HAART.
A little under 10,000 patients have been recruited to EuroSIDA at 72 treatment centres in Europe, Israel and Argentina. A total of 5728 patients (58%) were tested for HBsAg, and 498 (9%) tested positive for HBsAg. The highest prevalence of HBsAg patients was in Argentina (18%), followed by northern, central and southern Europe (9%) and eastern Europe (6%). Individuals with HBsAg were significantly more likely to be Caucasian (p = 0.02) and gay men (p
Median duration of HIV infection was longer in patients positive for HBsAg (five years) than HBsAg-negative individuals (four years, p 3 versus 275 cells/mm3, p
New AIDS and mortality
The incidence of new AIDS-defining events was comparable between individuals coinfected with hepatitis B virus (3.3 per 100 person years) and patients who only had HIV infection (3.4 per 100 person years). Even when the investigators included viral load in their statistical modeling, no significant difference was found between the two groups of patients.
All-cause mortality, however, was significantly higher amongst HBsAg-positive patients than HBsAg-negative individuals (3.7 per 100 person years versus 2.6 per 100 person years), with an adjusted incidence rate ratio of 1.53 (p = 0.001). A total of 31% of deaths amongst patients with HBsAg were AIDS-related compared to 43% of patients negative or HBsAg (p = 0.02). Liver-related causes accounted for 19% of deaths amongst patients with hepatitis B virus and 8% of individuals who only had HIV.
In further analysis, the investigators calculated that individuals with HBsAg were over three times more likely to die of liver related causes (IRR 3.5).
Response to HAART
Investigators also established that an increase in CD4 cell count of 50% after starting HAART reduced the risk of death by 40% in patients with HBsAg (p
Individuals with HBsAg started HAART with a lower median CD4 cell count (206 cells/mm3 versus 247 cells/mm3). Nevertheless, the proportion of patients achieving a viral load below 400 copies/ml and an increase in their CD4 cell count of 50 cells/mm3 or more was comparable between patients who were positive for HBsAg and HBsAg-negative.
“The prevalence of hepatitis B virus infection in the EuroSIDA cohort is 9%. HBV-HIV-coinfected patients experience similar responses to HAART as did those infected only with HIV”, note the investigators.
They also conclude, “this study confirms that hepatitis B virus infection increases significantly liver-related mortality in HIV-positive patients. This implies that every HIV-positive patient should be screened for hepatitis B virus and advised for prevention. Interventions to decrease mortality related to liver disease in HIV-positive patients with chronic hepatitis B virus, such as early initiation of HAART regimens targeted against both HBV and HIV, deserve further investigation.”
Konopnicki D et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in EuroSIDA. AIDS 19: 593 – 601, 2005.