Coinfection

AIDS 2014: AbbVie 3D Regimen Cures Most Genotype 1 HIV/HCV Coinfected Patients

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An all-oral regimen of 3 direct-acting antivirals plus ribavirin taken for 12 weeks demonstrated a sustained virological response rate of 94% for people coinfected with HIV and genotype 1 hepatitis C in the TURQUOISE-I study, according to a late-breaking report at the 20th International AIDS Conference (AIDS 2014) this week in Melbourne, Australia.

HIV/HCV coinfected people generally experience more rapid liver disease progression than people with hepatitis C alone and do not respond as well to interferon-based therapy. Direct-acting antivirals that target different steps of the HCV lifecycle offer the prospect of shorter treatment, fewer side effects, and higher cure rates for HIV/HCV coinfected as well as HCV monoinfected patients.

Mark Sulkowski from Johns Hopkins University School of Medicine and colleagues conducted the Phase 3 TURQUOISE-I trial to evaluate the safety and efficacy of AbbVie's 3D direct-acting antiviral regimen for HIV/HCV coinfected patients.

The 3D regimen consists of the HCV protease inhibitor ABT-450, a 100 mg boosting dose of ritonavir, and the NS5A inhibitor ombitasvir (formerly ABT-267) in a once-daily fixed-dose coformulation, taken with the twice-daily non-nucleoside HCV polymerase inhibitor dasabuvir (formerly ABT-333) and 1000-1200 mg/day weight-based ribavirin.

Prior to testing in coinfected patients, extensive drug-drug interaction studies in healthy volunteers showed that the AbbVie drugs have no clinically meaningful interactions with tenofovir or emtricitabine (the drugs in Truvada), atazanavir (Reyataz), or raltegravir (Isentress). The ritonavir in the ABT-450 coformulation also acts as a booster for atazanavir.

TURQUOISE-I is being conducted in 2 parts. Part 1 included 63 genotype 1 HIV/HCV coinfected patients. More than 90% were men, a majority were white, and the mean age was 51 years. The study enrolled both previously untreated people (about 67%) and prior relapsers (6%), partial responders (11%), and null responders (16%). About 90% had harder-to-treat HCV subtype 1a, about 25% had the favorable IL28B CC gene variant, and 19% had liver cirrhosis at baseline. They had undetectable HIV viral load on a stable antiretroviral regimen containing either atazanavir or raltegravir (45% and 55%, respectively), and the mean CD4 T-cell count was approximately 630 cells/mm3.

Participants in this open-label study were randomly assigned to take the 3D regimen plus ribavirin for either 12 or 24 weeks. The primary endpoint was sustained virological response, or undetectable HCV RNA at 12 weeks after completing treatment (SVR12). All patients in the 12-week arm and about two-thirds in the 24-week arm had reached this endpoint.

Results

The researchers concluded that the 3D regimen plus ribavirin was effective and well tolerated, and that these results are "highly consistent" with those previously observed in HCV monoinfected patients taking the same combination.

Part 2 of the TURQUOISE-I trial -- which will test the 3D regimen plus ribavirin in HIV/HCV coinfected patients taking the ritonavir-boosted HIV protease inhibitor darunavir (Prezista) -- will start later this year.

In response to question, Sulkowski agreed that people with easier-to-treat HCV subtype 1b probably do not need to include ribavirin with the 3D regimen, and most patients probably need only 12 weeks of treatment. The biggest concern, he said, is the group of hard-to-treat prior non-responders with subtype 1a and cirrhosis. Among the 6 patients like this in the trial, 4 achieved SVR12 but 2 experienced treatment failure.

7/21/14

Reference

M Sulkowski, JJ Eron, D Wyles, et al. TURQUOISE-I: safety and efficacy of ABT-450/r/ombitasvir, dasabuvir, and ribavirin in patients co-infected with hepatitis C and HIV-1.20th International AIDS Conference. Melbourne, Australia, July 20-25, 2014. Abstract MOAB0104LB.