Possible side-effects from long-term antiviral therapy

Hello all,
I have some questions to those of you with hepatitis B who are currently taking hep b medicine particularly Vemlidy.

1.) Do any of you experienced sever night sweats?
2.) how about fatigue and muscle aches after a 2 hours workout?
3.) Do any of you (female patients) had some changes on your monthly cycles? Mine seem to be getting lighter and short.

I seem to be getting a lot of night sweats now since I started Vemlidy in September of last year and at that time, my viral load was at 98 million and is currently down to 50 iu but my liver enzymes AST and ALT are still quite higher than normal.
I am 35 years old Asian female who is currently living in the UNITED STATES.

I was diagnosed in 2008 when I first came to the US but I never started taking any medicine for Hep B until July 2020 when I found out that my viral load was super high. I was feeling sick and tired before taking antiviral medicine but I never had night sweats and muscle aches even after working out for 2 hours. Your input will be appreciated. Thanks

Dear @Grithcel13,

You bring up important points in your questions, ones that I think many people are wondering about when considering treatment. I’ve moved it to its own thread so that people can search for it easily and also to focus discussion (I suspect this will be a very active discussion).

I personally have not felt any side-effects from my many years of daily tenofovir disoproxil, structurally fairly similar to the active component in Vemlidy (tenofovir alafenamide) as a 35 year old Asian male in Australia.

I do want to note it can be complicated linking the effects you feel specifically to the medication: generally (and this is the case here) you will be started on medication when your symptoms change, so there’s both the disease and the medication (and possibly whatever precipitated the change in symptoms - such as a changed immune response) that are contributing all together to how you are feeling.

I don’t mean to say that there are no side-effects associated with medications, but I do want to emphasise that you don’t want to stop/switch a medication that can potentially make you better because something else is making you feel worse. Timing is just one of the factors that can link your symptoms to the medications, but there are other factors to consider too.

Regarding the specific ones you mention, I would definitely feel fatigue and muscle aches after 2(!) hours of workout, but maybe you’re just much more fit than me. Given your AST and ALTs are higher than usual, that might be the reason. Your body may be spending a whole lot of energy trying to heal the liver damage that’s occurring, but generally we know that antivirals will act to normalise ALTs over time. Also, expending energy to heal will also generate heat, which might explain your night sweats.

Have you mentioned these concerns to your health care provider? If so, what was the answer you got back?


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Hi Thomas,

I herpes flare ups about every 2 months and have valacyclovir hcl 500mg available. I also have acyclovir cream, which is not as convenient to use as the former. My question: is it safe to take valacyclovir every time I have a flare up when I’m on TAF?


Dear @teh-minbrown,

Given that both of these drugs are processed by the liver and are excreted by the kidneys, this can increase the dose your body is getting of the TAF. You should perhaps confirm with your doctor whether it’s OK in your health situation to be taking them together. Otherwise it might be safer to use the topical cream.

Incidentally, it’s known that acyclovir/valaciclovir actually (very slightly) inhibits HBV levels as well. They in fact work similarly to entecavir/tenofovir/lamivudine: by messing with the virus DNA copying machinery. In the early days when we didn’t have these sorts of Hep B drugs, people were really struggling to find ways to inhibit the replication somehow and found these were better than nothing.

This was a common way to discover antiviral drugs. In fact, none of the Hep B drugs we use today were developed for Hep B infection. They have all been first developed and used against HIV, a completely different virus (but using the same sort of machinery and steps to replicate as HBV). They were found to work sufficiently well in Hep B infections as well.

Funding into Hep B research has also been quite low compared to other viruses, which has set the field back compared to other viruses. This makes it hard to do the work to find new drugs that work optimally for Hep B. It has also been hard to grow Hep B in the lab and simulate the way it sets itself up in an infected cell. Only in the last 10 or so years have we been able to infect lab cells efficiently enough to start screening for drug candidates. We are now just starting to see the fruits of this world-wide effort, so it’s a really exciting time.

@john.tavis is probably the guru here on this particular field and may have some more to add to this already long-winded story.


Hi Thomas,

I was surprised to read that Acyclovir/valacyclovir suppresses the replication machinery of hepatitis b virus. You’d think that taking them together would be a good thing. Maybe this is why my hepatologist says it’s safe to take them together. But I was concerned with renal toxicity as I am having a flare up just about every 2 months now, notwithstanding the fact that I’m on Vemlidy. I suppose it has to do with my weakened immune system as an older retired person.

Another question popped in my mind: my hep b surface antigen is in the high 800’s. My hepatologist says this puts me at a higher risk for HCC. I’m tested for it once a year, and there’s no sign of decreasing much less clearing it with treatment. Could you please explain the cause and effect relationship between the high number and the risk of hcc?

Thank you,

Dear @teh-minbrown,

I mean it all encapsulates how difficult it is to develop antiviral drugs: you have to know how things interact and can’t just go off on how it acts in a single instance.

I’m a little unclear about what you mean: when you talk about flares, do you mean flares in ALTs, flares in renal markers, flares in HBV, or cold sore flares?

With the link between HBsAg levels and HCC risk, the data from this has mostly been from correlation studies (e.g. https://www.sciencedirect.com/science/article/pii/S0016508512001722?via%3Dihub). Scientists measure the virus antigen and DNA levels of a huge number of people and if markers are different in those that get cancer vs. those that don’t.

As to what the mechanism (the cause and effect) actually is, the answer is we don’t know. There’s a whole bunch of educated guess-work, but the big problem is that we don’t really have a good lab model of HBV-associated cancer to actually be sure. I mean, this is a cancer that takes decades to form in a person, that’s something that’s really hard to study when you have grants that may run out in 2 years.


Hi Grithcel13!

I, too, am a female in the US who loves to exercise and am currently on Vemlidy (started in 2018). I initially had abrupt, acute headaches after starting the drug, but they eventually stopped after a few months. Other than that, I have had no other side effects.

I agree that it is very easy to attribute any deterioration in your health to the medication, but we can’t forgot that there are many other things that could be happening. I, too, have started to experience slight changes in my menstrual cycle in the past few months but am fairly certain it is due to my exercise and diet. I used to train for marathons and work out in the gym for hours in my youth (currently 41) and not have any issues but not so much anymore! I’ve been mostly lifting weights in the past 10 years, but after covid, I lost access to my gym and turned to stationary cycling at home with occasional weights. I started to rely on the bike a little too much for stress relief (up to 2 hrs a day) and as a result, my menstrual cycles got longer and longer. They’ve been 52 days the past 2 times and only bounced back to normal once during the Xmas holiday when I was less stressed, eating more and not exercising as much. In addition, I had a bit of a scare where they saw a mass on my latest ultrasound. But after getting an MRI, they determined it was a hemangioma so that was a relief! While waiting for the results, I started to have anxiety attacks, my digestion slowed down, I was nauseous and had chronic headaches… Once I found out the mass wasn’t cancer, I slowly got back to my normal health but it was a great lesson to learn. It’s amazing how your body will respond to perceived stress! I’ve really started to work on my stress levels since then and feel much better for it. I even got an Oura ring to help me work on my recovery and sleep and it’s kind of fun to see what things I can do to help improve my HRV.

I’ve also read that AST and ALT can be elevated for up to a week after intense exercise so maybe get tested after you’ve rested a few days and see if that makes a difference.



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Hi @Grithcel13, I want to add that at age 35 years believe it or not your night sweats could be an early symptom of menopause. Many women are in a state of “peri-menopause” years before they are full into menopause, which can only definitively be diagnosed by testing your hormone levels. I’m a 62 year old Korean American who started with lighter periods, occasional night sweats probably around your age and wasn’t diagnosed until mid-40’s by my GYN that I was full on into menopause. So your night sweats and lighter periods is something to discuss when you have your next GYN exam. Also, I’ve been on Vemlidy orTAF for 3 years and like Thomas, have had no discernible side effects since switching from Viread or tenofovir diprovoxil. I would definitely stay on Vemlidy rather than Viread because it’s associated with bone loss and increasing the risk of osteoporosis (which is why my doctor switched me - since taking Vemlidy, my osteoporosis has significantly been reduced!). Thanks for asking your good questions and hope to hear more from you. Always, Joan

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Dear @Joan_Block or anyone who has taken tenofovir (TDF) and Vemlidy (TAF), I would really like to hear your thoughts on these 2 drugs. I need to start treatment. My hepatologist has been willing to postpone treatments til now (I am 47) because although my DNA fluctuates between 500-3000, my ALT, ultrasound, and fibroscans have been ok. He thinks TDF can cause kidney problems. When I asked how long does it take before that occurs he said it can occur early on or later but that with monitoring it has been manageable with no one needing dialysis. I plan to switch doctors but I don’t want to delay treatment any longer. He says if I can afford Vemlidy, he thinks it would be better if I take it. But it would cost $85/month vs $10/month for TDF. I heard of the bone loss with TDF, but isn’t that reversible once TDF stops? I am at risk for osteoporosis anyway based on my stature and family history. I am tempted to start TDF and switch when I run into problems to save $ but if it is better, I can afford Vemlidy. I just wanted to delay spending so much for it as it will be 10 years before a generic of it will be available. I also found Gilead offers a coupon but do not know how much I will qualify for. Thanks in advance for your input.

Dear @hope4us, I was on TDF for almost 10 years before switching to TAF. The only reason I switched was because my osteopenia was progressing to osteoporosis. So my hepatologist changed me to TAF 2 years ago, and my bone density test showed significant improvement in my osteoporosis! I never had any kidney problems and this can be monitored easily with the blood tests that you get done (BUN, creatinine levels).

Gilead, which manufactures TAF, has a “Co-pay Coupon Program” that covers a lot of the cost of TAF. With my prescription plan and this coupon program, I actually don’t pay anything for my monthly supply! I didn’t know about it, but the specialty pharmacy my prescription insurance company uses enrolled me! So you can talk to your doctor about starting TAF and having either your doctor or pharmacy sign you up. The tele number on my Vemlidy co-pay coupon card is 1-877-627-0415. Call them.

Otherwise, I think your idea of starting on TDF until TAF becomes a generic isn’t a bad idea if for some reason you can’t pay less than $85. Your doctor can easily track your renal function while taking TDF and I think once you turn 50 years, you start getting dexa scans that measure your bone density for osteopenia or osteoporosis as well.

Stay in touch about this! Always, Joan

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Wow, thanks so much for your detailed response. I really appreciate your input.

Hi hope4us,

I am on Vemlidy (TAF) as well and had concerns about affording the medication. I had no experience dealing with pharmacies and obtaining prescription drugs, especially a speciality one like TAF with such an exorbitant cost. I decided to buy some time by enrolling in a clinical trial that provided me with TAF for free for 2 years as long as I was willing to come in for bloodwork every 3 months and a fibroscan yearly. But after that, I had to buy the drug on my own and was pleasantly surprised to discover the Co-pay Coupon Program that Joan mentioned. It covers 5000 toward the cost of the drug yearly.I 'm lucky that I live in a state that allows that cost to go towards my deductible so I end up not having to pay anything out of pocket for the drug. Hopefully, this program will help you as well!

Good luck!



@Rebecca, Thank you for taking the time to respond. I am a pharmacist so drug cost is on my radar. I had to use a drug manufacturer coupon for my kid’s acne before and after a while they no longer offered the coupon. I called the coupon program. They could not say how long this coupon will be offered. But I will cross that bridge then. It is nice to have options. The coupon covers up to Max of 5000/year on out of pocket costs. So glad for the coupon!

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