Researchers found that viral load can predict SVR rates nearly 1 month into DAA therapy.
Kay M. Johnson, MD, MPH
The viral load measured in hepatitis C (HCV) patients after 4 weeks of treatment with direct-acting antiviral (DAA) drugs is a strong predictor of sustained virologic response (SVR), new research suggests.
Researchers wrote that detectable below quantification (DBQ) and detectable above quantification (DAQ) week 4 viral loads (W4VL) are very common in real-world practice, making them the rate a strong predictor reduced SVR across genotypes and clinically relevant patient subgroups.
University Associate Professors Kay M. Johnson, MD, MPH and George N. Ioannou, MD, MS, FAASLD, associate professors of medicine at the University of Washington, and a third colleague from the Veterans Affairs (VA) Puget Sound Healthcare System in Washington set out to determine the extent to which W4VL predicts SVR in a real-life setting.
Before the advent of DAA drugs, levels of HCV RNA were assessed to determine whether a patient was responding to often difficult-to-tolerate interferon-based therapies, Johnson, told MD Magazine. The goal was to see if treatment was working so that it could either be stopped or continued longer to increase the chances of success.
In the era of highly effective DAAs, it became unclear whether to measure HCV RNA, the amount of virus in the blood, the researchers noted. To investigate how would the results be used during treatment, the team identified 21,095 patients within the VA healthcare system who had begun DAA-based antiviral treatment from January 1, 2014 to June 30, 2015.
The researchers classified W4VL into 4 categories: undetectable; detectable below quantification (DBQ); detectable above quantification (DAQ), where the viral load was 42 IU/mL or less; and DAQ, where viral load was greater than 42 IU/mL.
They found that W4VL was undetectable in 36.1% of patients. W4VL was DBQ in 45.6%; DAQ at 42 IU/mL or less in 9.3%; and DAQ at more than 42 IU/mL in 9.1% of patients.
“Although W4VL of greater than 42 was very strongly associated with lower likelihood of SVR, the absolute SVR rate of 86.2% was still very high in these patients,” Johnson said. “Our results suggest that antiviral treatment should not be discontinued early based on a W4VL that is detectable and quantifiable at greater than 42.”
Patients in the other 3 categories showed even better responses. Among those with an undetectable W4VL, 93.5% achieved SVR. In those with W4VL that was detectable but too low to quantify, 91.8% reached SVR. And in patients whose W4VL was DAQ at 42 units/mL or less, 90% achieved SVR.
Ioannou, Director of Hepatology for the VA Puget Sound Healthcare System, noted that treatment might be extended in some cases.
“For patients who were projected to be treated for only 8 weeks, we think it is reasonable to extend the treatment to 12 weeks if the W4VL is positive and above the level of quantification,” he told MD Magazine.
As to why W4VL was detectable and even quantifiable more frequently in the VA study than in clinical trials, the researchers suggested that trials may enroll patients with lower risks who are more compliant with treatment. Their viral loads could fall more quickly.
Another important difference could be the tools used to assess viral load. Three randomized trials the team investigated used an assay that was less sensitive for detecting extremely low levels of the virus.
“Providers should be aware that the assay used at their facility will affect DBQ and DAQ rates,” Johnson said.
Ioannou said further research should be conducted on 2 new regimens recently approved by the US Food and Drug Administration (FDA): sofosbuvir/velpatasvir (Vosevi); voxilaprevir; glecaprevir/pibrentasvir (Mavyret).
Mavyret is approved for only 8-week regimens in patients of all genotypes who do not have cirrhosis and have not previously been exposed to DAAs other than sofosbuvir, Ioannou said.
“We are interested to know if W4VL is an important predictor of SVR in these regimens and specifically whether the 8-week regimens should be extended to 12 weeks if the W4VL is above the level of quantification,” he said.
Ioannou stressed that ceasing therapy early is not advisable.
“Treatment should never be stopped prematurely before the entire course is completed, unless the patient is experiencing serious adverse events or has other life threatening comorbidities,” Ioannou said.
Johnson noted that antiviral drugs can suppress HCV and make viral levels in the blood undetectable fairly quickly.
“But there may still be viruses in the tissues of the body,” Johnson said. “It takes 8 to 12 weeks of the medication to kill all these hidden viruses. So stopping the DAA too soon will allow these hidden viruses to reproduce and the infection to come right back.”
The study, "Implications of HCV RNA level at week 4 of direct antiviral treatments for hepatitis C," was published online in the Journal of Viral Hepatitis this month.