Treatment with sofosbuvir/ledipasvir (Harvoni) was well tolerated and cured
all pregnant women with hepatitis C virus (HCV), according to a study presented
at the Conference on Retroviruses and Opportunistic Infections (CROI 2019) this
month in Seattle.
While 'baby boomers' have traditionally had the
highest rate of hepatitis C in the United States, HCV incidence is rising among
younger people, tracking
the ongoing opioid epidemic. This means more women of childbearing
age are infected with HCV and at risk of transmitting the virus to their babies,
but there has been little research on the use of direct-acting antivirals as
treatment for this group.
Dr Catherine Chappell of Magee-Women's
Hospital at the University of Pittsburgh Medical Center and colleagues conducted
a phase I pilot study to evaluate the safety and efficacy of sofosbuvir/ledipasvir
in pregnant women.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
Over the last decade, hepatitis C rates among pregnant women receiving care at Magee have doubled and in the
past several years at least 2% of all women who delivered at the hospital had
HCV, Chappell said. Currently there is nothing to offer these women for their
own treatment or to prevent perinatal transmission. But pregnancy is a "window of opportunity"
for health care that could potentially include hepatitis treatment, she added.
enrolled pregnant women with genotype 1, 4, 5 or 6 chronic HCV infection; those
with HIV or hepatitis B co-infection were excluded. They were enrolled at about
six months into pregnancy. The US Food and Drug Administration did not allow
treatment of women who were newly pregnant, according to Chappell, as drugs
taken by the mother can potentially have a more harmful effect on the foetus during
Out of 29
women screened for the study, most did not join because they had HCV genotypes
2 or 3 (10 women), continued to use illicit drugs (four women) or for other
reasons. In the end, nine women were enrolled. All were white and the median
age was 31 years (range 25 to 38 years). One had been perinatally infected
herself and the other eight had used injection drugs, including four who were on
medication-assisted treatment for addiction. All but one had HCV genotype 1a.
Participants were treated with once-daily
sofosbuvir/ledipasvir (400/90mg) for 12 weeks. The study took a long time to
enrol and at the start this was the only ribavirin-free regimen available,
Chappell noted. The main study endpoint was sustained virological response (SVR), or
continued undetectable HCV RNA three months after completing treatment, which
is regarded as a cure.
treated women experienced rapid response, Chappell reported. Eight women were
cured and one is still completing SVR follow-up. All nine carried their
pregnancies to term and all had undetectable HCV at the time of delivery. All
but one of the infants were delivered at term and were of normal weight. None
of the infants show evidence of HCV infection, including five who have been
followed for a year.
Treatment with sofosbuvir/ledipasvir was
safe and well tolerated. All treatment-related side-effects were mild or
moderate. To date, no safety concerns have been identified in infants exposed to the drugs
during gestation, Chappell said.
While it appears safe and effective, Chappell
said that larger studies are needed before this treatment approach can be
recommended. Noting that a substantial proportion of women were not eligible
for the study because they had HCV genotypes 2 or 3, she highlighted the
importance of studying pangenotypic regimens in pregnant women, such as sofosbuvir/velpatasvir
(Epclusa) or glecaprevir/pibrentasvir (Maviret). She also recommended integration of HCV therapy and addiction
treatment into prenatal care.