Does daily dosage of Valtrex affect validity of herpes test results?

Dear Doctor,

I am a female in my mid-20s.  In January of this year, I had an enlarged lymph node in my groin and flu-like symptoms.  I was tested for HSV II (blood serum test) and my results were negative.  My doctors thought I had the flu and not herpes.  However, my partner (with whom I ALWAYS used a condom) at the time also underwent HSV II testing after I told him about my symptoms and his results were positive.  Thus, I underwent a second HSV II blood serum test.  The results were positive.

Ever since my diagnosis (February 10, 2010), I have taken 500 mg of Valtrex daily.  I have never had an outbreak or any visible lesions.  I have, however, felt tingling every once and a while and a slight ache in my labia.  At the onset of these symptoms, I would increase my dosage to 1000 mg twice per day.

I was tested (blood serum) a third time last week and received my test results today.  I tested negative for every SDT, including HSV II.  Confirmatory tests were also administered, and both the initial and confirmatory tests were negative.  My  nurse practitioner told me that I do not have HSV II (or any other SDT) at this time and that the second test with the positive result must have  been in error.  She said that it is possible that I am carrying the virus, but that I have not built up any antibodies that would produce a positive test result.

My questions are as follows:  (1) does the fact that I have been taking 500 mg of Valtrex per day affect the validity of my test?; (2) if so, how long should I stop taking Valtrex before being tested again?; and (3) assuming Valtrex DOES NOT affect the validity of test results, should I still be tested again?

Thank you.

[H. Hunter Handsfield, M.D.]

Welcome to the STD forum.

The direct answer to your opening question is yes, valacyclovir (Valtrex) sometimes can affect the HSV blood test.  However, probably not in the way you describe here.  If someone has new HSV-2, treatment with valacyclovir (or any of the other anti-HSV drugs) can delay the conversion of the blood test from negative to positive.  However, once the test is positive, treatment cannot make it negative again.

There is a good chance you do not have HSV-2 at all -- i.e. I agree with your insightful and wise NP.  Most results that are apparently positive and later become negative were never truly positive at all.  And I agree with your own doctors about your illness with the fever and inflamed lymph node -- probably it wasn't an HSV-2 infection.

We probably can sort this out if you would like to provide more detail about both your HSV-2 blood test results and your partner's.  Most HSV blood tests have numerical results, not just "positive" or "negative".  Try to find the exact numbers for HSV-1 and HSV-2, for your partner and for all 3 of your blood tests.  My prediction is that your "positive" result is a low number that would suggest a false positive result.  Perhaps it will be the same for your partner as well.  Whether or not you need additional testing will depend in part on the detailed results to date.

In the meantime, why are you taking valacyclovir anyway?  There are 2 reasons for suppressive therapy.  One is to control symptoms.  But you aren't having outbreaks, so no need there.  (If you stop the drug and start having outbreaks, you can always restart the drug.)  The other reason is to prevent transmission to partners.  If you are still with the partner describe above, there is no point; he is alreayd infected and people cannot "ping pong" HSV back and forth.  However, if you are now sexually active with other partner(s) whose HSV-2 status isn't known, treatment would be reasonable.  But only if you really have HSV-2.  Don't stop the drug on my say-so, but this is also something to discuss with the NP.

I look forward to helping further if you want to post all those test results.  In the meantime, you could discuss this business with your NP -- even consider printing out the thread as a framework for discussion.

Regards--  HHH, MD

[seekinganswers8]

Doctor,

Here are my results to date:

(Quest Diagnostics)
Collected: 01/19/10
Reported: 01/20/10
HSV 2 IGG Herpesselect Type specific:  .26

(Quest Diagnostics)
Collected: 02.04.10
Reported: 02.08.10
HSV 2 IGG Herpesselect type specific AB Inhibition:  >5.00
HSV 2 IGG Herpesselect type specific AB: >5.00

(LabCorp)
Collected: 09.09.10
Reported: 09.14.10
HSV 2 type specific Immunoblot:  Negative

As of Friday I stopped taking Valtrex and Lysine. I also started eating foods high in arginine, such as peanut butter and coconut. So far, I have felt fine and have no visible signs of an outbreak. I am concerned, however, because my February results were not borderline. I appreciate any guidance you can give me. Thank you.

[H. Hunter Handsfield, M.D.]

Thanks for the clarifications.  You are correct that your February result is not borderline, as I had expected it would be.  Combined with your January symptoms, I would have concluded you had initial genital herpes due to HSV-2, despite lack of genital lesions at the time.  That your partner apparently turned out to have a positive HSV-2 test supported that conclusion.  (However, I still would be interested in seeing his detailed test result, if you can learn it.)

Another slighly puzzling factor here is that I don't know exactly what test LabCorp did.  The most commonly used HSV immunoblot is produced by Focus, the same company that makes HerpeSelect.  However, Focus is a subsidiary of Quest labs, and I am pretty certain LabCorp doesn't use any Quest/Focus products.  (For sure they don't do HerpeSelect.)  Therefore, I am at a loss to judge the reliability of the immunoblot result.

At this point, you need the HSV Western blot test, the ultimate gold standard to sort out uncertain HSV blood test results.  WB is done primarily (only?) at the University of Washington lab where it was developed and studied, but all labs know how to refer specimens to secondary labs.  I suggest you ask your doctor to send it through Quest; and if you want to really ice the cake, as for a HerpeSelect immunoblot (not ELISA) by Quest, in addition to the WB at UW lab.  (However, this might be a bit more expensive, and your insurance co. might not understand or approve what they might consider "extra" testing.  But you can always save this exchange to show to the insurance co. if they deny coverage.)

I am glad to hear you're off Valtrex for the time being.  While off treatment, be alert for localized genital itching or sores; if that happens, see your doc immediately (within a day, if possible) for lesion testing for HSV.  Discuss it ahead of time with your doc, so the office is prepared to see you the same day without an appointment.

As for lysine, arginine, etc -- it's quackery.  Well, maybe not quite true quackery, because there are theoretical scientific reasons that might suggest benefit.  But the research on clinical efficacy is quite clear:  absolutely no effect on frequency or severity of recurrent HSV outbreaks.  In addition, more recent research has called into question even the theoretical science in support of lysine/arginine.

Keep me posted as new information evolves.

[seekinganswers8]

Thank you for your prompt response.  I saw both my NP and my PCP (the one who made the diagnosis) today.  Neither of them really knew what to do or say.  The PCP thinks that my negative status is the result of one of three scenarios: (1) the February 2010 test was in error; (2) Valtrex has worked so effectively on me that I have no detectable viral load; or (3) although exposed, my immune system, perhaps in conjunction with Valtrex, miraculously fought the virus off.  There is of course a fourth scenario- the most recent LabCorp test is wrong.  My PCP advised that because, in her opinion, the Valtrex could be suppressing my antibodies to an indetectable amount, that I wait for 6 week to 3 months before getting tested again.  I am confused, however, in light of your initial analysis; if I at one time theoretically had enough antibodies to produce a >5.00 result, and those antibodies don't disappear, then why would that affect the validity of this test result?

Should I wait to get my blood retested, or should I just go ahead and do it now?

[H. Hunter Handsfield, M.D.]

Your providers have an incomplete understanding of HSV.  Errors always are possible in lab testing, so scenarios 1 and 4 are possible.  2 and 3 are not.  All HSV infections are lifelong, and treatment never eradicates the virus.  A positive result always indicates infection, not "exposure; there is no HSV test that shows.

There really no need to wait before additional testing is done.  A Western blot at this time will sort things out once and for all.

I'll be happy to comment once again when you have additional test results to report, including your partner's HSV-2 result.  But there won't be much more to say until then.

[seekinganswers8]

I went back to the NP at my OB/GYN this afternoon to undergo additional testing.  LapCorp (I cannot afford Quest's $475 test not covered by my insurance) didn't know what the Western Blot was or how to get it to Washington.  So, I personally googled the contact information for the UW lab on my iphone in the office to get the info.  The lab tech my NP and I spoke with said that he had to send a "kit" to us first with instructions on how to ship the sample prior to shipping.  Is it really this hard? What am I missing? I just want to know whether I have herpes or not.

[H. Hunter Handsfield, M.D.]

No, it is not "really this hard" -- or shouldn't be.  You obviously weren't talking to the right people at LabCorp, and you're doing far more work than you should have to.  All your NP has to do is draw your blood in a red top tube, attach a LabCorp requisition and use the write-in section to request "HSV Western blot at University of Washington clinical lab, Seattle" and send it just like that to the local LabCorp facility.   (If it gets there and they don't know what to do, they'll call LabCorp central who will guide them further.)

[seekinganswers8]

Dr. Handsfield,

We ordered the Western blot test kit with shipping instructions, as the "Director" of LapCorp in my region, who spoke with my NP, said they wouldn't ship it.  Very strange, but I'll just have to wait.

In the interim, I went back on my Valtrex because I felt worn down and felt the usual dull pain in my labia that is there 95% of the time.  I would've stayed off of it but for a big business trip I'm going on and have to be on top of my game for- didn't want to risk getting an outbreak if I do have HSV 2 or be stressed out worrying that I could be getting one.  

My question though is this: Is it possible to have a dull, yet essentially constant labia pain without lesions?  I feel it gets worse with the less sleep I get.  Is this more likely psychosomatic, or real in your opinion?  This is pain that I experience literally 90% of the time.

Thank you for your help thus far.

[H. Hunter Handsfield, M.D.]

Herpes doesn't cause persistent pain of this sort.  The association with sleep pattern is most consistent with a psychological origin -- and so is your own statement psychosomatic pain:  whenever a person suggests his or her own symptoms have a psychological origin, usually s/he is correct.

[seekinganswers8]

Dear Doctor,

My OB/GYN just called me.  The lab at UW called back with my Western Blot test results.  They told her that the antibody count was so low that it was "indeterminate" and that I would have to be tested again in 16 weeks.

I stopped the Valtrex, with the exception of the day or two as mentioned above.  So far I have been okay.  What do you think?  I am so confused.

[Still_Worried_]

Just bumping this up so he won't miss it since it's been a couple of days  =]

[seekinganswers8]

Thanks Still_Worried_.

Dr. Handsfield- just following up.  I would really like to know your medical opinion on this, especially since you recommended the Western Blot test as the gold standard in HSV testing.  Please let me know-- I need to know whether I have HSV 2 or not.  My doctors here are at a loss, and you are much more knowledgeable than them (in my opinion). They don't know what to tell me.  Please help.

[Still_Worried_]

Hmmm....He must be busy.  I don't think you'd have to pay to post another since it pertains to the same question & it has been less than 60 days.

[H. Hunter Handsfield, M.D.]

Sorry for the delayed reply.  I have been traveling in Zimbabwe for STD/HIV research and training, with variable success getting on line.

The most likely scenario is that you do not have HSV-2.  Before you have another WB in 16 weeks, I recommend you ask your NP to phone the UW lab and speak directly to the chief supervisor in charge of HSV WB testing.  (I can't post her name publicly, but will pass it on to MedHelp administration; use the Contact link to get in touch with them.)  She might be able to give you a definitive answer now, or more personalized advice about further testing.

Alternatively, or if your NP doesn't feel confident in all this, try contacting the Westover Heights Clinic of Portland, OR (www.westoverheights.com), which is directed by Terri Warren, moderator of MedHelp's herpes forum.  WHC may agree to mediate this, and they know exactly whom to speak with at UW.  In either case, you can print out all or parts of this thread for the lab, WHC, or both.

Finally, I will ask Terri herself to scan this thread (again) and add any comments she considers appropriate.  In the meantime, try to not let the uncertainty weigh too heavily on you.  Most likely you don't have HSV-2.

[seekinganswers8]

Thank you Dr. Handsfield.

The chief supervisor at the lab said that they would have to redraw and retest in 12 to 16 weeks and compare the structures they saw in the September 2010 sample with the new sample to determine whether there is any change.  From there they'll allegedly be able to determine whether the structures are HSV 2 antibodies or non-specific viral antibodies.  Finally, the chief supervisor said that the use of anti-virals such as Valtrex can slow the serological change even in my case, where my purported infection occurred in January 2010.  Is this true?  This just seems kind of crazy- I have been tested now 4 times, the last of which was the WB.  Do you recommend that I be retested a fifth time in 12 to 16 weeks?  Am I some sort of 21st century medical conundrum?  Why can I not be provided with a definitive diagnosis at this point after spending hundreds and hundreds of dollars on testing?

[Terri Warren, RN, Adult Nurse Practitioner]

Hi Seeking answers,
This is Terri Warren from the herpes board.  Dr. Handsfield wrote me about your post and said I could jump in here if I wanted to.  Hope you don't mind!
We do lots of herpes testing in our clinic, about 20-25 tests per week.  All tests with an index value of 1.1 to 3.5 get referred to western blot at UW.  It is not all that uncommon for someone who has an index value in this range to get back an indeterminate result.  More often, the answer is clear, but about once every other month, we get an indeterminate result.  It isn't completely clear why this happens, but there are a few reasons:

1) the patient has some other substance in their blood, perhaps a similar antibody, that is tripping the test just a little, but artificially.  If a follow-up test done at 6 months from the first one and run in parallel as the lab states is necessary, is still indeterminate, I think the feeling generally is that the test is really negative.

2) The taking of Valtrex could influence the result.  I don't know about since January, but I think it is important to come off your Valtrex completely.  Don't go back on it when you feel abnormalities in the vaginal area, but just stay off.  If you develop an actual sore or lesion, then you should immediately have it swabbed.  View this as another opportunity for getting an accurate diagnosis.

3) You are actually infected and for some reason, even the western blot is not giving you an accurate answer.  We have had patients here who have had a positive swab test but an indeterminate western blot for a while.  This has happened twice to us in the past two months.  It had only happened to us twice previously at this clinic.  I suspect it is truly a rare event that the western blot would miss the infection, but we know that no test is perfect.  

The truth is that you may have to live with uncertainty for a while.  This is true because your boyfriend is indeed positive, if I am reading your previous posts correctly.  

I hope this gives you a little perspective from a place that uses these tests extensively.  Sorry you have to live with this uncertainty, but remember that herpes is not dangerous and if you have it, it will not shorten or endanger your life.  I would be happy to help you in any way that I can if you need me, just call the clinic and set up a consult.

Terri

[simplyconcerned]

This a very interesting situation. I hope everything for your next time come out fine. This actually leaves me in further limbo of should I take the medicine ( due to not spreading it to someone else) or staying off to get a accurate result. My igg level came back a 1.7 and my biokit test came back with a very very faint pink dot. I will be following up on your story and hoping the best for you.

[H. Hunter Handsfield, M.D.]

So there it will lie for a few weeks.

MedHelp's software closes a thread to new comments if there are no comments for 2 months.  To avoid that, please come back with a very brief comment once or twice before your repeat WB in 4 months, so that when that result comes you will be able to post it and I can comment one last time.  But otherwise let's close the thread until the result is available.

In the meantime, stay cool; remember that even if you are infected, HSV-2 has a lot less impact on most infected persons' lives than you migth assume.  Try to put aside the "poor me/why me?" thoughts.  It just happens sometimes when people are tested for HSV. We all wish the science of HSV testing were more precise than it is, but it's not a self esteem challenge!