Opportunistic disease and mortality in patients coinfected with hepatitis B or C virus in the strategic management of antiretroviral therapy (SMART) study

Clin Infect Dis. 2008 Dec 1;47(11):1468-75. doi: 10.1086/593102.


Background: In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4(+) cell count is <250 cells/microL) group, compared with the viral suppression (continued use of antiretroviral therapy) group. We assessed whether participants with concurrent hepatitis had an increased risk of the end points evaluated in the SMART study.

Methods: Participants were classified as being positive for hepatitis B virus (HBV) if they had positive hepatitis B surface antigen results for >6 months and positive for HCV if they tested HCV antibody positive. The rate and hazard ratio (HR) of OD and/or death and its 2 components were compared by hepatitis status and drug conservation versus the viral suppression group.

Results: Among 5472 participants enrolled from 8 January 2002 through 11 January 2006, 930 (17%) were HBV positive and/or HCV positive. The relative risk of non-OD death in participants randomized to the drug conservation group versus the viral suppression group was comparable regardless of hepatitis status (HR for coinfected and HIV-monoinfected participants, respectively, 1.9 [95% confidence interval {CI}, 1.0-3.9 and 1.8 [95% CI, 0.9-3.4]). The rate of OD or death was 3.9 events per 100 person-years in the coinfected group and 2.0 per 100 person-years in the HIV-monoinfected group. This excess risk was due to a higher risk of non-OD death among the coinfected participants (HR, 3.6; 95% CI, 2.3-5.6), whereas the risk of OD was comparable (HR, 1.1; 95% CI, 0.7-1.8). The 3 leading causes of non-OD death in coinfected participants were unknown cause, substance abuse, and non-acquired immunodeficiency disease cancer.

Conclusions: Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess risk.

Trial registration: ClinicalTrials.gov NCT00027352.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / administration & dosage
  • Anti-Retroviral Agents / therapeutic use*
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy*
  • Hepatitis B / complications
  • Hepatitis B / epidemiology*
  • Hepatitis B / mortality*
  • Hepatitis B Surface Antigens / blood
  • Hepatitis C / complications
  • Hepatitis C / epidemiology*
  • Hepatitis C / mortality*
  • Hepatitis C Antibodies / blood
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Risk Factors


  • Anti-Retroviral Agents
  • Hepatitis B Surface Antigens
  • Hepatitis C Antibodies

Associated data

  • ClinicalTrials.gov/NCT00027352