MELBOURNE, Australia — Results from 2 clinical trials evaluating interferon-free hepatitis C regimens have good news for patients coinfected with HIV. Investigators presenting here at the 20th International AIDS Conference shared promising results from TURQUOISE-1 and PHOTON-2.
"One thing that we have learned in this era of hepatitis C treatment is that if there is no virus detected 12 weeks after stopping therapy, it is highly unlikely that we will see the same virus re-emerge," TURQUOISE-1 presenter Mark Sulkowski, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, told Medscape Medical News. "We believe these are virologic cures, although there will be more follow-up."
In the randomized open-label TURQUOISE-1 study, investigators evaluated a triple direct-acting antiviral regimen consisting of ABT-450 — a type of protease inhibitor — coformulated with ritonavir and ombitasvir in a single tablet taken once a day. Dasabuvir, a non-nucleoside polymerase inhibitor, was taken twice a day. All patients received ribavirin as well.
Patients were treated for 12 or 24 weeks, and the primary end point was sustained virologic response 12 weeks after treatment cessation. The study involved 63 patients, all of whom had their HIV infection well controlled with antiretrovirals.
"Patients were on antiretroviral regimens that included raltegravir or the PI atazanavir," Dr. Sulkowski explained. "If they were on atazanavir, the boosting of atazanavir was done with the 3-drug combination."
Only patients with hepatitis C genotype 1 were involved in TURQUOISE-1. In the 12-week treatment group, the sustained virologic response 12 weeks after treatment cessation was 93.5%.
In the 24-week treatment group, the sustained virologic response 4 weeks after treatment cessation was approximately 97%, which is "highly consistent with responses seen in hepatitis C patients who are not coinfected with HIV," Dr. Sulkowski pointed out.
Out of the 63 patients receiving treatment in TURQUOISE-1, only 3 patients did not achieve a durable virologic response.
Virologic failures occurred in 2 patients, and 1 patient withdrew consent. However, no patient stopped treatment because of adverse events, and there were no serious adverse effects during the 12- or 24-week dosing intervals.
In the open-label nonrandomized and uncontrolled PHOTON-2 study, 274 patients coinfected with hepatitis C genotypes 1 to 4 and HIV received sofosbuvir 400 mg a day plus a weight-based ribavirin dose, ranging from 1000 to 1200 mg a day. Patients with compensated cirrhosis were also included in the study.
Duration of treatment was 12 or 24 weeks, depending on the causative genotype and whether or not the patients had received treatment for hepatitis C.
A wide range of antiretroviral regimens were allowed, but the backbone regimen consisted of tenofovir plus emtricitabine.
The primary efficacy end point was sustained virologic response at 12 weeks. Sustained virologic response was defined as serum HCV below 25 copies/mL 12 weeks after the cessation of hepatitis C therapy.
Sustained virologic response at study end point was over 80% for the 4 genotypes treated in PHOTON-2, and for treatment-naive and treatment-experienced participants.
Table. Sustained Virologic Response at 12 Weeks
Sustained virologic responses 12 weeks after the cessation of treatment were lower in patients with cirrhosis than in those without liver damage, at least for patients with a variant of genotype 1, said presenter Jean-Michel Molina, MD, from the University of Paris.
A total of 38 patients did not achieve a sustained virologic response 12 weeks after treatment cessation; of these, 31 relapsed. One patient had virologic breakthrough and 6 were lost to follow-up or withdrew.
Rates of grades 3 and 4 adverse events were low in the 12-week and 24-week treatment groups (5% and 6%, respectively). Grade 3 and 4 laboratory abnormalities did occur in approximately 20% of both treatment groups, but only 1 patient in the 24-week treatment group had a hemoglobin level below 8.5 g/mL.
No patients required modification of their antiretroviral regimen, although transient decreases in CD4 cell counts were observed, Dr. Molina pointed out.
In all, 3% of participants discontinued treatment because of adverse effects.
Sofosbuvir is active against most genotypes, Dr. Molina emphasized. "It is effective in these 4 genotypes, and there are no interactions with HIV drugs, so you don't have to worry about drug interactions. A lot of physicians would like to have their patients on all-oral therapy, which is what we can offer today with these new drugs."
Investigators are planning to initiate a multicenter international study to evaluate the triple-drug oral regimen plus ribavirin in coinfected patients later this year.
For years, there wasn't much progress in hepatitis C treatments, said Suman Majumdar, MD, from the Burnet Institute in Melbourne, Australia. "The results that are coming through are quite promising," he told Medscape Medical News.
Unaffordable Cost Per Cure
In an editorial in the HIV/AIDS-themed issue of JAMA, published to coincide with the meeting, Michael Saag, MD, from the University of Alabama School of Medicine in Birmingham, writes that although new data represent a "quantum leap forward" in the treatment of patients coinfected with hepatitis C and HIV, "the current cost of the regimen makes wide-spread use unaffordable."
When combined with ribavirin, the average wholesale price of a 12-week course of treatment is $94,500; for a 24-week course, which was used in the PHOTON study, the price is $189,000, he nots. "Industry analysts indicate that the pricing of the drug is not based on the cost of ingredients or the duration of therapy, but rather the cost per cure."
With more than 185 million hepatitis C virus seropositive people worldwide, and 4.4 million in the United States alone, "the world simply cannot afford to pay on a cost per cure basis, especially when the majority of persons with chronic infection, an estimated 75%, do not progress to cirrhosis or end-stage liver disease over 20 to 30 years," Dr. Saag points out. "Hopefully competition among the new products coming to market in the next 18 months will result in substantially lower pricing for the drugs."
20th International AIDS Conference. Abstracts MOAB0105LB and MOAB0104LB. Presented July 21, 2014.
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Cite this: Oral Hepatitis C Drugs Helping Patients Coinfected With HIV - Medscape - Jul 25, 2014.