Treatment of HIV+ subjects co-infected with hepatitis B or C: safety and efficacy comparison of ABT 378/r versus nelfinavir from a phase III blinded randomised clinical trial

This was a multicentre, international, double-blinded randomised study of 653 ARV – na¥ve subjects treated with either ABT- 378/r 400/100 (n = 326) mg bid or NFV 750 mg tid (n = 327), each arm receiving d4T and 3TC in addition. Those with AST/ALT > 3 ULN at screening were excluded from the study. Fifty-seven (17%) ABT 378/r and 68 (21%) NFV subjects were positive for Hep B surface antigen and/or hepatitis C antibodies.

At week 40 94% of ABT378/r and 82 % of NFV had HIV RNA levels < 400 copies/ml. Of those who were Hep B/C positive 91% in the ABT-378/r group and 76% in the NFV had HIV RNA < 400 copies/ml. Overall 4% of subjects across both groups developed Grade 3 / 4 elevations of AST/ALT. Incidence of grade 3/ 4 elevations in the Hep B/C positive subjects were 6/57 (12%) for ABT-378/r and 13/68 (20%) for the NFV group.

Those who were Hep B/C positive had a higher incidence of Grade 3 / 4 elevations of AST/ALT than those who were B/C negative, however there was no discontinuation due to elevated liver enzymes or clinical hepatitis. Efficacy and other safety results were generally similar in both B/C positive and B/C negative groups.

Comment

No TDM data was shown for these individuals. It may of proven useful for those with Grade 3 / 4 elevations to see if they were outside the therapeutic range and whether dose adjustment would of helped.

TDM has been useful in individual dosing of other PI’s for co-infected individuals and should be considered. However as ABT 378/r is co formulated individualized dosing may prove more difficult.

J. Arribas, C. Barros, J. Gonzalez-Lahoz, W. Cameron, R. Rubio, F. Altice, B. Clotet, M. King, P. Cernohous, J. Moseley, M. Sattler, B. Bernstein and E. Sun for the M98- 863 study team.