By Liz Highleyman

Liver disease related to coinfection with hepatitis B or hepatitis C virus (HBV or HCV) is an increasingly important cause of illness and death among people with HIV.

At the 4th International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention last week in Sydney, Australia, researchers presented 2 studies of HIV-HBV and HIV-HCV coinfected participants in the large SMART study, which looked at structured interruption of antiretroviral therapy vs continuous treatment.

The SMART study enrolled 5472 participants with CD4 cell counts above 350 cells/mm3. Within this group, nearly 17% also had hepatitis B or C:

• 110 were coinfected with HBV (2.0%);

• 798 were coinfected with HCV (14.6%);

• 14 had both HBV and HCV (0.25%).

Subjects were randomly assigned either to stay off treatment as long as their CD4 cell counts remained above 350 cells/mm3 and resume therapy when they fell below 250 cells/mm3 (the drug conservation arm) or to receive continuous therapy without interruption (the viral suppression arm).

As previously reported, the study was halted in January 2006, after an interim analysis revealed that patients who interrupted treatment had a significantly higher risk of opportunistic illness and death, as well as a slightly higher risk of cardiovascular, liver, and kidney problems.*

Study 1

In the first study, Ellen Tedaldi and colleagues compared the incidence of opportunistic and non-opportunistic illnesses and death in the coinfected and HIV monoinfected patients.

Results

• HBV or HCV coinfected individuals and HIV monoinfected subjects had a similar relative increase in the risk of opportunistic or non-opportunistic disease or death in the treatment interruption compared with the continuous therapy group:

- hazard ratio 2.58 for coinfected and 2.57 for HIV monoinfected patients for opportunistic disease or death;

- hazard ratio 1.78 and 1.69, respectively, for non-opportunistic disease.

• Overall, there were few deaths due to opportunistic disease in either coinfected or HIV monoinfected patients.

• Death rates were comparable in the 2 groups (0.14 vs 0.8 per 100 person-years).

• Coinfected patients had nearly a 4-fold higher risk of death due to non-opportunistic disease compared with HIV monoinfected subjects (2.52 vs 0.69 per 100 person-years).

• Though they made up just about 17% of the total study population, coinfected patients accounted for nearly half of all deaths due to non-opportunistic disease.

• Findings were similar when only patients with hepatitis C were analyzed separately.

• The main causes of non-opportunistic death among coinfected patients were substance abuse and non-AIDS defining cancers.

• Coinfected patients had more deaths due to liver or kidney disease, while HIV monoinfected patients had a slightly higher rate of cardiovascular disease.

• Coinfected participants were significantly more likely to have an unknown cause of death.

The researchers concluded that interruption of antiretroviral therapy may be particularly harmful for patients coinfected with hepatitis B and/or C, who already have a higher underlying risk of death due to non-opportunistic causes.

Study 2

In the second study, Greg Dore and colleagues looked at the likelihood of restarting HAART among HIV-HBV coinfected, HIV-HCV coinfected patients, and HIV monoinfected.

Several antiretroviral agents - including 3TC (lamivudine, Epivir), emtricitabine (Emtriva), and tenofovir (Viread) -- are active against both HIV and HBV, so HIV-HBV coinfected patients who interrupt HAART regimens containing these agents are at risk for progression of both diseases.

Results

• HIV-HBV confected subjects were significantly more likely to restart HAART and did so sooner after treatment interruption than either HIV monoinfected or HIV-HCV coinfected patients.

• This was predominantly due to a faster decline in CD4 cell counts in the HIV-HBV group.

These results suggest that HIV-HBV coinfected patients may experience faster HIV disease progression after stopping HAART. But it is difficult to draw firm conclusions, since this group was small, in part because the SMART investigators discouraged enrollment of patients who needed antiretroviral drugs to control HBV as well as HIV. The researchers are currently analyzing study data to determine whether HBV DNA increased in patients who underwent treatment interruption.

National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain; School of Public Health, University of Minnesota; Copenhagen HIV Programme, Hvidovre University Hospital, Copenhagen, Denmark; Institute of Infectious and Tropical Diseases, Brescia, Italy; Medizinische Universitaetsklinik, Bonn, Germany; Montreal Chest Institute, Royal Victoria Hospital, Montreal, Canada; Temple University School of Medicine, Philadelphia, PA; Royal Free and University College Medical School, London, UK; Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

07/31/07

References

E Tedaldi, M Puoti, J Neuhaus, andothers. E et al. Opportunistic disease and mortality in patients coinfected with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) in the SMART (Strategic Management of Antiretroviral Therapy) study. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract TUAB203.

G Dore, V Soriano, J Neuhaus, and others. Higher rate of antiretroviral therapy reinitiation among HIV-HBV coinfected patients in the episodic therapy arm of the SMART study. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract TUAB204.

* W M El-Sadr, J D Lundgren, J Neaton, and other (the SMART Study Group). CD4+ Count-Guided Interruption of Antiretroviral Treatment. New England J Medicine 355(22): 2283-2296. November 30, 2006.

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