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Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine
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January 17, 2023
Highlights
• In Egypt and Ukraine, universal screening and treatment in pregnancy may improve both maternal and infant outcomes
• The proportion of women cured by delivery would be 65% in Egypt and 70% in Ukraine, versus 0% with standard of care
• The proportion of infants infected at the age of 6 months would decrease by 50% compared to standard of care
• Assuming that DAAs are safe and efficacious for use in pregnancy and can help
prevention of vertical transmission, we found that universal screening and treatment of all pregnant women would result in the largest number of women diagnosed in pregnancy and being cured by delivery, and a significant decrease in the number of HCV-RNA positive infants at 6 months of age as compared to all other alternative strategies of targeted/universal screening with deferred or targeted treatment.
Pregnant women and paediatric populations are at risk of being left behind as DAAs are not approved for use during pregnancy or lactation or in early childhood. In LMIC settings the duration of breastfeeding is often long and women may have pregnancies in quick succession, which can lead to long delays before women are eligible for treatment, increasing the risk of disease progression, VT and loss to follow up.
CHC is a major problem in women of childbearing age, with the increased risks of poor outcomes in pregnancy, including higher risk of intrahepatic cholestasis, preterm birth, and low birth weight. There is also the estimated 5% risk of vertical transmission (VT) of HCV, which increases further among women with unsuppressed HIV coinfection or high levels of HCV-RNA.
Whilst finding from the first DAA trials in non-pregnant adults reported a decade ago, there is only one published pharmacokinetic study of the non-pangenotypic sofosbuvir/ledipasvir in 8 pregnant women; all treated in the 2nd/3rd trimester, and all achieving HCV cure, with no vertical transmission or safety issues. An ongoing sofosbuvir/velpatasvir pharmacokinetic study in 10 women currently recruiting, with treatment initiated from 14-22 weeks’ gestation, will report in 02/2023, and a single arm safety (n=100, USA) of 3rd trimester sofosbuvir/velpatasvir, conducted in the same site, will report in 2025. If DAAs are found to be safe and efficacious in pregnancy, it provides a unique opportunity to screen women, and initiate treatment and cure women during pregnancy, which will potentially reduce the risk of VT and adverse maternal and infant outcomes associated with HCV. Recent surveys of pregnant women in Egypt and Ukraine have found high acceptability of routine HCV screening in antenatal care and likely high uptake of DAAs if approved for use in pregnancy. Assuming that HCV treatment during pregnancy is safe, our aim was to explore the potential impact of different HCV screening and treatment strategies on maternal and infant HCV outcomes in Egypt and Ukraine using a Markov model developed and applied to each setting.
Abstract
Background & Aims
Hepatitis C (HCV) test and treat campaigns currently excludes pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting-antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine.
Methods
Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, WHO risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission (VT)); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected.
Results
S0 resulted in the highest proportion of women undiagnosed:59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatmentduring pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70% respectively), and lower levels of VT (3.4% and 3.6% respectively).
Conclusions
This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes.
Impact and implications
In the context of two lower middle-income countries with high HCV burden (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy.
Assuming DAAs in pregnancy reduced vertical transmission, model findings indicate optimal maternal and infant benefits with provision of universal (rather than risk-based targeted) screening and treatment during pregnancy: the proportion of women diagnosed and cured by delivery would be 65% in Egypt and 70% in Ukraine (versus 0% with standard of care), and the proportion of infants that would be infected at the age of 6 months would decrease from 6.5% to 3.4% in Egypt, and from 7.9% to 3.6% in Ukraine, compared to standard of care.
While future trials are needed to assess safety and efficacy of DAA treatment in pregnancy and impact on VT, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical in informing policymakers in improving screening and treatment recommendations for pregnant women
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