By Liz Highleyman

HIV-HBV Coinfection

This picture shows the structure of the Human Immunodeficiency Virus(HIV).

This picture shows the structure of the Hepatitis B Virus (HBV).

Due to overlapping transmission routes, many people are infected with both HIV and hepatitis B virus (HBV). This is especially the case in parts of the world -- such as Africa and Asia -- where hepatitis B is endemic, and in resource-limited settings where HBV vaccination is not widespread.

Response to HAART

A retrospective cohort study reported in the December 1, 2008 issue of Clinical Infectious Diseases evaluated the impact of chronic hepatitis B on HIV virological response, changes in CD4 cell count, hepatotoxicity, and mortality among patients receiving HAART through a workplace program in South Africa during 2001-2006.

Participants were antiretroviral-naive and received HAART according to the program protocol, consisting of efavirenz (Sustiva or Stocrin), zidovudine (AZT; Retrovir) and lamivudine (3TC; Epivir -- a drug with activity against both HIV and HBV).

On the basis of pre-HAART serum testing, patients were classified according to hepatitis B surface antigen (HBsAg) status (negative or positive) and HBV DNA level (< or > 10,000 copies/mL). A total of 537 individuals fulfilled the inclusion criteria; 431 (80.3%) were HBsAg negative -- indicating they did not have chronic hepatitis B -- while 106 (19.8%) were HBsAg positive. In the latter group, 60 (11.2%) had low HBV DNA and 46 (8.6%) had high HBV DNA.

Participants were followed for up to 72 weeks. Relationships between HBV status and HIV RNA suppression, changes in CD4 cell count, mortality, and hepatotoxicity -- defined as transaminase (ALT and/or AST) levels 5 or more times the upper limit of normal -- were assessed using regression techniques.

Results

• Participants in the HBsAg negative, HBsAg positive low HBV DNA, and HBsAg positive high HBV DNA groups had similar rates of HIV viral load suppression > 400 copies/mL (P = 0.61), CD4 cell count increases (P = 0.75), and mortality (P = 0.11) for up to 72 weeks after HAART initiation.

• Baseline transaminase levels were highest in the group with high HBV DNA (P = 0.004).

• Frequency of hepatotoxicity was similar in the HBsAg negative group and the HBsAg positive low HBV DNA group, but higher in the HBsAg positive high HBV DNA group (incidence rate ratio 4.4).

• Serious grade 3 or 4 liver toxicity was uncommon overall (23 patients total).

• The highest hepatotoxicity rate was observed in the HBsAg positive high HBV DNA group (17 per 100 person-years) compared with the HBsAg low HBV DNA group (1.7 per 100 person-years) and the HBsAg negative group (3.8 per 100 person-years).

"We revealed that HBV status does not affect HIV RNA suppression, CD4 cell count response, or mortality during the first 72 weeks of HAART in an African setting," the investigators concluded.

But, they added, "The risk of HBV-associated hepatotoxicity, however, is associated with the baseline HBV DNA level."

The researchers noted that most instances of serious transaminase elevation occurred within 6 months of starting HAART -- and were likely attributable to immune reconstitution inflammatory syndrome -- but 3 cases occurred after 6 months.

In an accompanying editorial, Vincent Soriano of Hospital Carlos III in Madrid, Spain, and colleagues wrote that given the high rate of hepatitis B in the South African population, all HIV positive individuals should be screened for HBV, and those who are HBV negative should receive the hepatitis B vaccine.

While several studies have shown poorer CD4 cell recovery after starting antiretroviral therapy in patients with HIV-HCV coinfection -- though data have been mixed -- this does not appear to be the case for HIV-HBV coinfected individuals.

Aurum Institute for Health Research and Toga Laboratories, Johannesburg, South Africa; University of Pretoria, Pretoria, South Africa; Johns Hopkins University School of Medicine, Baltimore, MD; London School of Hygiene and Tropical Medicine, London, UK.

Liver Disease Progression

In a related study presented at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) this past fall, investigators looked at liver disease progression -- necroinflammatory activity and fibrosis -- among HIV-HBV coinfected patients in South Africa.

A total of 30 HIV positive patients with chronic hepatitis B who had previously undergone liver biopsy were selected, and were compared to a group of 30 HIV negative control subjects with chronic hepatitis B monoinfection matched for age and HBV serological profile.

In both groups, 63% were hepatitis B "e" antigen (HBeAg) positive and 37% were HBeAg negative. The HIV-HBV coinfected group had relatively advanced HIV disease, with a median CD4 count of 117 cells/mm3.

Results

• The median alanine aminotransferase (ALT) level at the time of biopsy was 118 U/L in the coinfected group and 104 U/L in the HBV monoinfected group, a non-significant difference.

• Necroinflammatory activity was significantly greater in the HIV-HBV coinfected group compared with the HBV monoinfected group (median 7.6 vs 4.6 on the Ishak modified Histological Activity Index scale; P = 0.0002).

• Liver fibrosis scores were also significantly greater in the coinfected compared with the HBV monoinfected group (median 3 vs 1; P < 0.0076).

• Findings were similar regardless of HBeAg status.

"Hepatitis B related necroinflammatory activity and fibrosis was significantly greater in HIV-HBV coinfected than in HBV monoinfected patients," the researchers concluded. "This was despite advanced immunosuppression in the coinfected group and similar transaminase levels and HBV viral loads in both groups."

This finding, they added, "may predict for a worse long term liver morbidity and mortality outcome in coinfected patients in the setting of endemic HBV infection."

1/09/09

References

CJ Hoffmann, S Charalambous, DJ Martin, and others. Hepatitis B Virus Infection and Response to Antiretroviral Therapy (ART) in a South African ART Program.
Clinical Infectious Diseases 47(11): 1479-1485. December 1, 2008. (Abstract).

V Soriano, P Rivas, and M Nunez. Risks and benefits of using antiretroviral therapy in HIV-infected patients with chronic hepatitis B in developing regions. Clinical Infectious Diseases 47(11): 1486-1489. December 1, 2008.

MW Sonderup, H Wainwright, HN Hairwadzi, and others. A clinicopathological comparison of HIV/Hepatitis B co-infection and Hepatitis B mono-infection in Cape Town, South Africa. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 1936