Coinfection

AIDS 2012: HIV/HBV Coinfection Linked to Higher Mortality, More ART Liver Toxicity

Approximately 6% of people with HIV receiving antiretroviral treatment in Tanzania were coinfected with hepatitis B virus (HBV), which was associated with an elevated risk of death, smaller CD4 T-cell gains, and greater likelihood of liver toxicity, researchers reported at the recent XIX International AIDS Conference (AIDS 2012) in Washington, DC. alt

An estimated 6% to 20% of HIV positive people in sub-Saharan Africa are thought to be coinfected with HBV. People with HIV are less likely to spontaneous clear HBV and experience faster progression to advanced liver disease, including cirrhosis and hepatocellular carcinoma. But the effect of HBV coinfection on response to antiretroviral therapy (ART) has not been well studied, especially in Africa.

Claudia Hawkins from Northwestern University and colleagues assessed the prevalence of HBV in a cohort of HIV positive adults at 18 sites in Dar es Salaam who were receiving ART in the PEPFAR-supported Management and Development for Health program. They were followed from November 2004 through September 2011.

Two-thirds of the HIV monoinfected participants and half of the HIV/HBV coinfected patients were women, with an average age of about 36 years. The median CD4 count was low, at about 110 cells/mm3. HIV/HBV coinfected patients who also tested positive for hepatitis C virus were excluded, but only about half were screened. About 17% with HIV alone and 10% with HIV/HBV coinfection were also undergoing treatment for tuberculosis.

All participants were antiretroviral-naive and received a local standard first-line ART regimen consisting of either:

  • stavudine (d4T; Zerit) or zidovudine (AZT; Retrovir) + lamivudine (3TC; Epivir) + nevirapine (Viramune);
  • tenofovir (Viread) + lamivudine or emtricitabine (Emtriva) + efavirenz (Sustiva) or nevirapine.

Lamivudine, emtricitabine, and tenofovir are active against HBV as well as HIV, and are therefore preferred drugs for coinfected patients; 3% of HIV monoinfected and 17% of HIV/HBV coinfected patients were on an ART regimen containing tenofovir.

Results

  • 1079 of 17,539 HIV patients in this analysis were coinfected with HBV, for a prevalence rate of 6.2%.
  • Compared with HIV monoinfected patients, HIV/HBV coinfected patients were younger, more likely to be male, had a lower median CD4 cell count, and had a higher ALT level prior to ART initiation.
  • 1572 people with HIV alone and 130 coinfected people died during follow up, for overall mortality rates of 6.16 and 7.74 deaths per 100 person-years, respectively.
  • HIV/HBV coinfected patients had a significantly higher risk of death in a univariate analysis (unadjusted hazard ratio 1.28; P = 0.007).
  • However, after adjusting for other factors including age, sex, HIV disease status, CD4 count, high ALT, body mass index, and TB status, there was only a trend towards higher mortality in the coinfected group (adjusted hazard ratio 1.18; P = 0.07).
  • Mortality for both HIV monoinfected and HIV/HBV coinfected patients was much greater within the first 6 months on ART, with more than 60% of deaths occurring during this time.
  • CD4 cell gains were similar in the 2 groups after 6 months on ART (77 vs 71 cells/mm3, respectively), but were significantly greater in the HIV monoinfected group at 12 months (158 vs 143 cells/mm3, respectively).
  • 2.0% of HIV monoinfected patients and 3.8% of coinfected patients experienced liver toxicity defined as ALT > 120 IU/L; 0.6% and 1.8%, respectively, had ALT > 200 IU/L.
  • The liver toxicity incidence rate was about twice as high in the coinfected group (ALT > 120 IU/L: 1.29 vs 2.49 events per 100 person-years, respectively; ALT > 200 IU/L: 0.43 vs 1.16 events per 100 person-years, respectively).
  • HIV/HBV coinfected patients had a significantly higher likelihood of ALT > 120 IU/L and > 200 IU/L, in both univariate and adjusted multivariate analyses.

"Antiretroviral treatment outcomes are impacted by the presence of HBV," the researchers concluded, as indicated by lower CD4 counts throughout the course of immune restoration, almost 20% higher risk of mortality, and higher risk of moderate-to-severe hepatotoxicity.

8/21/12

Reference

C Hawkins, B Christian, J Ye, et al. Prevalence of hepatitis B co-infection and response to antiretroviral therapy among HIV-positive patients in urban Tanzania. XIX International AIDS Conference (AIDS 2012). Washington, DC, July 22-27, 2012. Abstract MOAB0101.