Many people are probably aware of the U = U campaign for HIV, basically that undetectable viral load = untransmissible. I’m wondering if we have sufficient evidence to conclude the same thing for HBV. We have substantial evidence that viral suppression with nucleos(t)ide analogues reduces the risk of transmission, because we recommend it to prevent perinatal transmission, and also to prevent healthcare workers living with hep B from spreading it to their patients.
I haven’t personally heard of anyone with undetectable HBV DNA spreading it to someone else via accidental exposure to small amounts of blood (blood transfusions are a different story), but I also know that hepatitis B is 50-100x more infectious than HIV, so less virus is needed to cause infection.
Hi @et5656,
This is a great question. I will guess that this is not possible with HBV due to how complex it is. HIV is well understood and studied, but that is not the case for HBV. There is a great deal about HBV that remains unknown. U=U is effective, depending on high antiviral adherence. I won’t be surprised if there are more people on HIV treatment compared to HBV. I hope it is the case, because we can reduce exposure rates. Best, Bansah1
Right, I’m almost certain that there are more people on treatment for HIV than the number of people on treatment for hepatitis B, and I agree with you that hep B research is underfunded. So it’s entirely possible that we haven’t actually studied the concept of U=U for hepatitis B.
Still, even if antiviral treatment reduces risk of transmission by 98% (just a guess — not sure what the actual percentage is), it still feels like we should spread the word and take into account the prevention of HBV transmission when considering whether or not to start patients on antiviral treatment. It feels like this topic would be especially applicable to younger people who are more likely to be HBeAg+ with higher viral load.
I agree 100%. Unfortunately, we have not done a great job at increasing hepatitis B education and raising awareness. An increase in education and awareness will improve prevention and treatment rates while reducing stigma and discrimination.
However, stigma, funding, and lack of political will continue to be issues holding us back. We have the heart and know what to do; we need the power and resources to make things better for everyone. Great topic. Best, Bansah1.
Right, I also think that public health officials want to know if it’s cost-effective to put people on treatment. If someone with HBV spreads it to someone else, there’s a cost associated with that. It’s not clear to me whether or not this is taken into consideration when developing treatment recommendations. It seems like the treatment recommendations are developed to prevent outcomes like cirrhosis and liver cancer for the patient being treated. These indications for treatment are still very important, but I’d argue that it’s not 100% of the picture.
I want to be clear that I’m not insisting that everyone with HBV must be on treatment, but I think that if we prove that it’s cost-effective for more people to be on treatment, this will help to convince the government/health insurance programs to cover the cost of medication, thus making it more accessible to people.
Hi Eddie, I do think U=U can apply to HBV transmission to some degree. Take my grandma for an example; when her DNA load dropped and she gave birth to my mother, my mother did not get infected. However, my mother’s elder sister got a chronic infection. We assumed that it was because of the DNA load, or we can’t explain why my aunt got HBV while my mother doesn’t have it. My mother was born in the 1970s, when we didn’t have any measures to prevent mother-to-child transmission. We didn’t have vaccines then. My grandma cleared her virus years after this.
Hepatitis B is 50-100 x more infectious than HIV –yes but I think this is because HBV can survive well in the environment. HIV can’t survive long after it gets out of human bodies. Even in some cases, HIV gets into human bodies and still survives, it may not be able to find a receptor before it dies. That makes it harder for HIV to transmit than HBV. However, we have vaccines for HBV, which cut the transmission routes to the next generation. HIV is an RNA virus, and its surface antigen can change much … For HBV, the surface antigen is relatively stable, which makes vaccines highly effective. It doesn’t matter if the virus load is something *10^8 or something *10^2, as long as the HBsAb is greater than 10 IU/L, they are protected. Vaccination is so effective that public health issues focus on immunisation rather than antiviral treatment. After years of living with my aunt and my cousin (my aunt’s daughter, they both have chronic infection and high DNA load), I am still healthy.
And let’s talk about U= U again. There are many cases in China where low virus loads didn’t lead to any infection. I know some friends’ husband/boyfriends have HBV infection but dna load under 200IU/mL and my friends’ HBV test remain all negative. However, we can’t say that a virus load of < 10 IU/mL doesn’t lead to any infection for certain, because no human experiment can be conducted. We can say that a low virus load means a lower risk of transmission.
I agree with you that it makes sense to focus on hepatitis B vaccination as the first line of defence. Though as a person living with HBV, it’s not safe to assume that everyone around me is vaccinated – in fact, most people over the age of 30 are not. I still think U=U could be useful (if we have empirical evidence to support it), because let’s say that I start dating someone new, and they haven’t had the hep B vaccine yet. Assuming I’m able to convince them to start the vaccine series, it would still take months for them to develop full protection. I actually didn’t know until a few years ago that taking antiviral medication reduced risk of transmission at all, but if I had known that in my early 20s, I would have had a lot less anxiety about spreading hep B.
This is a great question and one that we have been thinking about.
It is likely that U= U is not absolute: some mouse studies have shown that if you inject a highly susceptible mouse with a large amount of blood of someone with HBV infection but undetectable viral load, there is still a chance that infection will occur. However, this is likely to be the same for HIV and blood transfusions, and U=U is still a thing for them.
I also think U=U would be helpful, but there is definitely controversy around the absoluteness of this. There have been studies done in HIV that have supported U=U that cannot be done in HBV. One major aspect was looking at “sero-discordant couples”, that is partners where one person is negative for the infection and the other positive. You can then study the likelihood that the negative person gets infected when their partner is taking antivirals or not and show that U=U.
However, for HBV, we have the vaccine which we would encourage the negative person to get. Because that has been so successful, it is impractical to recruit enough unvaccinated people to show if U=U.
We will have to be a bit more creative in which datasets to study to more properly study this phenomenon. That said, we act like U=U for clinicians who are doing exposure prone procedures, so maybe we just need to be louder in the community to help the affected community.
Interesting. I didn’t think that U=U applied to blood transfusions for HIV. You raise a good point that I hadn’t thought of about the feasibility of testing our hypothesis that U=U for HBV. I would never tell anyone who I’m dating that they don’t need the vaccine because I’m on antivirals, nor would I ever say that to anyone else who is dating a person with HBV. They should just go get the vaccine.
It would also be difficult to study sexual partners whose vaccination status is unknown. People with HBV (on antivirals) certainly have sex with people who don’t have HBV without talking about it first, but this likely tends to happen more in casual relationships where it would be hard to get the HBV-negative person to agree to participate in such a study.
Yes, it is difficult to ethically do these studies in a randomised control study. Much of the justification from HIV and U=U have come from observational studies, which as mentioned above are going to be very complicated for HBV even in populations with higher risk (e.g. people with multiple sexual partners and do not wear protection).