Why do we wait until 28 weeks to start antiviral therapy for pregnant mothers?

I think it’s great that we use antiviral therapy to reduce the risk of transmission for women with a high viral load, since post-exposure prophylaxis (vaccine alone, or vaccine + HBIG) can sometimes fail under these conditions. It kind of feels like we should be starting sooner than 28 weeks of pregnancy though. If the baby is born prematurely, there won’t be much time before delivery for the antivirals to start to reduce viral load. It can also be difficult to predict which babies will be born prematurely. Sure, there are some indications, such as twins/triplets, or people who have a history of preterm birth, but these are not guarantees.

In my opinion, there’s also a difference between someone who has a viral load of 500,000 vs 500 million. Treatment would be indicated for both, but the person with 500 million would need treatment for a lot longer to bring the viral load to “acceptable” levels.

Additionally, in some resource-limited countries, HBIG is not routinely available, and even HBV DNA tests can be prohibitively expensive, and only the basic screening test is available. Without HBIG, it feels like achieving a low viral load is even more important. Shouldn’t we prescribe antivirals to all HBsAg+ mothers in such situations? I also understand that antivirals may be expensive, but they are likely more accessible than HBIG, thanks to HIV treatment/prevention programs, which are generally more established and better funded than HBV treatment/prevention programs. For what it’s worth, if I was in that situation and couldn’t get Viread, I’d accept Truvada as an alternative in a heartbeat.

I guess I can’t really think of a downside of starting treatment earlier (e.g. 20 weeks), but it seems like there are some pretty clear downsides to waiting.

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Great question. I think it may have to do with the safety and effectiveness of the antivirals. It will be interesting to understand the evidence behind this. Best, Bansah1

Hi @et5656,

Great question and I’d welcome any @HealthExperts to comment on this.

My understanding is that it is an extension of a general precaution to limit medications as much as possible during the development phase of a fetus and only give the antivirals when they are effective for limiting transmission (2nd or 3rd trimester). That said, you are correct that treatment during the entire pregnancy is safe (e.g., Efficacy and safety of continuous antiviral therapy from preconception to prevent perinatal transmission of hepatitis B virus | Scientific Reports )

Hope this helps,

Thomas

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Define printing, the guidelines is now recommending starting treatment to the beginning of the second trimester. If the Patent is not already on turn off of beer.

Thank you
ROBERT G Gish MD

1 858 229 9865

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Agree earlier treatment at beginning 2nd Trimester is being recommended, however if unable to start until 28 weeks due to cost or logistics is still effective at reducing viral load before delivery and preventing mother-to-baby transmission

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Another question related to this:

Why do we tell people who start antiviral treatment to prevent perinatal transmission that they can stop after the baby is born, when we tell people who start for literally any other reason that they must continue taking it until HBsAg loss?

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Hi @ et5656

This is a great question. In my experience with iTAP2 study by PHPT Thailand (J Gonzague et al ) in 2022( Maternal short course TDF and infant vaccine to prevent MTCT of HBV) which study in 504 cases with HBsAg and HBeAg +ve pregnant women and started TDF from 28 weeks of gestation through 2months postpartum and then discontinued.

From the study, it was found that there were less than 1% of pregnant women with severe hepatitis flare (AST/ALT > 10 times ULN) at 4 months postpartum after stopping TDF and when we followed and closed monitoring, all AST/ALT returned to normal limit without intervention within 1year .This may be due to the fact that treatment with TDF in short duration (from 28 weeks of gestation to 2 months after delivery) less than 6 months can suppress HBV DNA viral load to some extent while if we start TDF from the beginning of pregnancy until delivery which is longer term course of treatment, it may suppress HBV DNA viral load to undetectable in most pregnant women and may leading to more rebound HBV replication to severe hepatitis flare after stopping TDF. Therefore, there may be potential safety risks associated with the use of long duration TDF in these pregnant women.

Recently, AASLD guidelines for HBV management recommended starting early TDF at 16 weeks of gestation for eligible high risk MTCT pregnant women with HBsAg +ve in clinical settings where HBIG is unavailable. I hope this helps for your question.

chul_chan

Chulapong Chanta. MD. Pediatrics.

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I agree, this is a great question and I would love to hear more @HealthExperts or @ScienceExperts to comment because I don’t get it either. None of the justifications have ever felt really convincing to me and indeed WHO guidelines now suggest that mothers who give birth can continue on with their antiviral therapy post-partum.

TT

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Indeed there are 2 options, either stop prophylaxis at delivery or continue long-term, this will become therapy and not prophylaxis. Both have pros and cons, your hepatologist will discuss with you. However, the probability of achieving hbsag loss during long term NUC is limited

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