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Raltegravir Efficacy and Safety Through 3 to 5 Years With HBV or HCV Coinfection
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Raltegravir-based regimens proved efficacious and generally well-tolerated in antiretroviral-naive and experienced people coinfected with hepatitis B or C through 5 years of follow-up in the STARTMRK trial and 3 years of follow-up in BENCHMRK trials [1]. Liver enzymes rose more frequently in HBV/HCV-coinfected people than in HIV-monoinfected participants, but changes usually occurred in the first 48 weeks of treatment then leveled off.
Three trials established the efficacy of raltegravir--STARTMRK in antiretroviral-naive people and BENCHMRK 1 and 2 in treatment-experienced people with multidrug-resistant virus. All three trials enrolled HBV/HCV-coinfected people if they had alanine and aspartate aminotransferase (ALT and AST) and alkaline phosphatase levels at or below 5 times the upper limit of normal. BENCHMRK participants had total bilirubin at or below 2 times the upper limit of normal. All three trials remained blinded through 156 weeks.
Among 699 antiretroviral-experienced people in the BENCHMRK studies, 114 (16%) had hepatitis coinfection, including 6% with HBV, 9% with HCV, and 1% with both. Among 563 antiretroviral-naive people in the STARTMRK trial, 34 (6%) had hepatitis coinfection, including 4% with HBV, 2% with HCV, and 0.2% with both. Everyone in STARTMRK also took tenofovir and emtricitabine, which are active against HBV.
In the raltegravir arm of STARTMRK, 90.9% of coinfected people and 89.1% of monoinfected people had a 240-week viral load below 50 copies. In the efavirenz arm of STARTMRK, 91.7% of coinfected people and 80.0% of monoinfected people had a 240-week viral load under 50 copies.
In the raltegravir arm of BENCHMRK 1 and 2, 62.3% of coinfected people had a 156-week viral load below 50 copies, as did 57.9% of monoinfected people. In the placebo arm of the BENCHMRK trials, proportions with a viral load below 50 copies at 156 weeks were 14.7% in the coinfected group and 26.3% in the monoinfected group. CD4 gains were equivalent in coinfected and monoinfected people taking raltegravir or efavirenz in all three studies.
In all three trials, similar proportions of HBV/HCV-coinfected people and monoinfected people had any clinical adverse event. Proportions of people who stopped treatment because of an adverse event were slightly lower in coinfected people than in monoinfected people, except in the raltegravir arm of STARTMRK, in which discontinuation rates were 5.6% in coinfected people and 4.9% in monoinfected people.
At week 240 in STARTMRK, hepatobiliary events were more frequent with raltegravir than efavirenz in coinfected people (5.6% versus 0%) and in monoinfected people (5.7% versus 3.4%). At 156 weeks in the BENCHMRK trials, hepatobiliary event rates were lower with raltegravir than placebo in the coinfected group (2.7 versus 4.7 per 100 person-years) and lower with raltegravir than placebo in monoinfected people (2.0 versus 3.9 per 100 person-years). No coinfected person in any arm of the three trials stopped treatment because of a hepatobiliary adverse event, and under 1% of monoinfected people in each arm quit treatment for that reason.
Grade 3 and 4 AST and ALT elevations were more frequent in HBV/HCV-coinfected people than in HIV-monoinfected people in raltegravir arms, and often in the comparator arms:
Grade 3 and 4 AST elevations in HBV/HCV-coinfected versus HIV-monoinfected:
BENCHMRK raltegravir arm grade 3: 9.1% versus 3.4% (week 156)
BENCHMRK raltegravir arm grade 4: 2.6% versus 0.3% (week 156)
BENCHMRK placebo arm grade 3: 2.7% versus 3.0% (week 156)
BENCHMRK placebo arm grade 4: 0% versus 1.5% (week 156)
STARTMRK raltegravir arm grade 3: 5.6% versus 4.6% (week 240)
STARTMRK raltegravir arm grade 4: 5.6% versus 0.8% (week 240)
STARTMRK efavirenz arm grade 3: 0% versus 3.0% (week 240)
STARTMRK efavirenz arm grade 4: 6.3% versus 0% (week 240)
Grade 3 and 4 ALT elevations in HBV/HCV-coinfected versus HIV-monoinfected:
BENCHMRK raltegravir arm grade 3: 10.4% versus 3.6% (week 156)
BENCHMRK raltegravir arm grade 4: 3.9% versus 0.8% (week 156)
BENCHMRK placebo arm grade 3: 8.1% versus 1.5% (week 156)
BENCHMRK placebo arm grade 4: 0% versus 2.0% (week 156)
STARTMRK raltegravir arm grade 3: 0% versus 1.9% (week 240)
STARTMRK raltegravir arm grade 4: 5.6% versus 1.5% (week 240)
STARTMRK efavirenz arm grade 3: 6.3% versus 1.9% (week 240)
STARTMRK efavirenz arm grade 4: 6.3% versus 0.4% (week 240)
The researchers noted that most jumps in AST and ALT occurred during the first 48 weeks of treatment and that further increases were "minimal."
Reference
1. Rockstroh J, Sklar P, Zhao J, et al. Safety and efficacy of raltegravir over 3 years in patients co-infected with HIV and hepatitis B and/or C virus. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-885.
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