Still seeking information

Dr. Hansfield,
I asked this question a while back, but you  mentioned that there was a limit to the number of questions allowed.  To remind you my situation, after sixteen years of monogamy (except one instance of hand to genital contact) I tested positive for HSV-1 and 2.  I've never had an outbreak or even a coldsore.  I don't remember my HSV-1 titer, but the number on the HSV-2 was 7.6.  My wife tested positive for HSV-1 (she has oral cold sores) but negative for HSV-2.  I've read the valcyclovir transmission study and it seems that we have several protective factors: her hsv-1 status, sex frequency <5x per month, long length of relationship and long length of my infection.

I'm currently taking valacyclovir to prevent transmission.  Here are my questions (1) Is there any way to assess the risk to her if I were to quit the valayclovir (I would think the risk would be low given the above factors) (2) In a previous post you thought that the study design underestimated the valcyclovir protective effect.  Can you say specifically why?  (3) Is there any way that taking valcyclovir long-term could reduce my bodies (already) effective capacity to fight this virus.
Thanks for your reply.

[Edward W Hook, MD]

Dr. Handsfield and I share the forum.  This time you got me.  FYI, the reason we share the forum is because we have worked together for nearly 30 years and while our verbiage styles vary, we have never disagreed on management strategies or advice to clients.

I'll try to help. You are asking good questions and provide the information needed for me to try to help.  Your HSV-2 test results absolutely indicate that you have HSV-2.  I agree with you on the protective effects, including that you are currently taking daily valacyclovir, all combine to reduce your risk for transmission of infection.  I should also point out that while we DO know that each of these variables acts independently to reduce risk, how they all work together at the same time is not possible to estimate.  The fact that they work has been established through complex studies which have involved thousands of person, millions of dollars and years to complete.  To evaluate the effects of combined influence would require even more resources which, unfortunately, are not available, nor are they likely to be.  The total preventative effect of all that you are doing could be more than the sum of the individual contributions.  

So, now let's go to your questions:

1.  I agree that your risk would be low.  How low is hard to estimate.  Further, I would add that although you have not had an outbreak in over 15 years, experience tells us that when people taking the valacyclovir, they sometimes do have an outbreak pretty soon after that.

2.  The underestimate is because everyone who took part in the study was encouraged to use condoms, to avoid sex during outbreaks and had disclosed their infection status to their partners.  Thus, as I explained in my paragraph above, while we can be sure that the valacyclovir helps substantially, it may have been an underestimate.

3.  there are no data to suggest that taking valacyclovir reduces your body's immune response to infection.

I hope these comments are helpful.  EWH

[WilfredB]

I'm not sure that I understand your response.
1.  I think that you meant to say that "experience tells us that when people  ?quit? taking the valacyclovir, they sometimes do have an outbreak soon after that."  This is my concern, that the valacyclovir takes over and that the body's immune response is less engaged in fighting the infection.  Do you see what I mean?
2.  Your said that the study underestimates the protective imact of valacyclovir, but the fact that all of those interventions occurred simultaneously (disclosure, condom education, etc) makes me think that the actual impact of the valacyclovir might have been overestimated and that it's is hard to tease the specific impact out from the other interventions.  

[Edward W Hook, MD]

1,  The fact that people often have outbreaks following stopping valacyclovir does not mean that their immunity has been diminished.  If that were the case, after the initial recurrence off valacyclovir recurrences would become more frequent and that is not the observation.  The biology here is complex.

2.  Again, we're getting into statistical complexities which would take more space and detail than is appropriate for the Forum.  It related to the fact that the assumptions which are involved in the analysis tend to be conservative, making it statistically "harder" to prove that the drug was having an effect.

As I read your responses, I suspect the implication is that you want assurance that transmission is not likely to occur. While I agree that this is the case, please remember that statistics apply to groups, not individuals. Thus, if the odds of transmission are one in a million, if you are the one, that does not help you.  I cannot promise that transmission will not occur, with or without the measures you are taking.  The measures however do reduce the risk.  I hope this makes sense. EWH

[WilfredB]

Thanks, I understand the limits of clinical research regarding individuals vs groups. I am looking for some reassurance as I don't want to pass this on to my wife, but I'm also trying to make the right decision about the valtrex.  Since I've never been symptomatic with herpes.  It feels a little surreal to continue it daily.  It is also expensive.  Even though my  co-pay is low now that it is generic, it costs the health care system significantly for me to continue it.  It the evidence is not clear for me that it is protective of her then I would talk to her about stopping it, but if the best evidence that we have is that it is protective for her then I'll take it for the rest of my life if needed.

[WilfredB]

One last question (I promise), in people who have outbreaks and use valacyclovir for chronic suppression, is there any clinical or research evidence of resistance the the drug emerging over time.

[Edward W Hook, MD]

A comment, then an answer.  I provided the information I did in an effort to give you as much relevant information as possible because ultimately this is a decision you need to take yourself.  If you stop the valacyclovir you may not have a recurrence and, in fact, I suspect you will not.  I would suggest being off the drug at least a week before resuming sex, just to be on the safe side.

Second, you should discuss the situation with your wife.  How does she feel about the risk- this is critical.  Having made it for over 15 years without transmission, the odds are in your favor but her thoughts are important.  Feel free to share my comments.  

There are no data to suggest that use of valacyclovir for suppressive therapy regularly causes HSV resistance to the drug.  While most valacyclovir resistant HSV does occur in persons who have taken the drug but it is very rare.  I would not worry that your taking valacyclovir has caused resistance.  EWH

[WilfredB]

I would definitely talk with my wife before making any changes to the plan.  It seems like the best data suggests that continuing the valcyclovir is in her best interest.  I asked the question about resistance because I was trying to assess her best interest.  If I take it long term am I putting her at risk for drug resistant HSV.  It seems this is unlikely.

I am also hearing from you that, while taking the valacyclovir,  if I were to miss a dose accidentally then I should probably also avoid sex for a week because there might be some rebound in viral shedding.

No need for further reply unless you have additional opinions.
Thanks