difficult to control herpes outbreaks

[kjj122]

Hi. I am HSV-2 positive ( 2 years) and was started on valtrex for suppresion one year ago. On suppressive doses of 500mg per day  I continued to have recurrent outbreaks for the first three months of treatment. I was switched to 1000mg per day and again continued to have recurrences about twice per month with prodromal symptoms of tingling once per week. I believe that the only difference between my symptoms before and after starting suppression was the duration of the outbreak. Of note, my outbreaks have been in different locations - buttocks, inner thighs, labia. There is no predicting the location. My doctor suggested switching to famvir at 500 mg twice per day. I have been on this dose for three weeks and was doing well (no outbreaks) until this morning when I noted one my buttock. I immediatey took 1000mg and will repeat that this evening. I do not understand what is going on. I am not immunocompromised (HIV negative x many tests just because I have been concerned not that I'm at high risk). I realize that resistance to these medications can occur in people who are immunocompetent, but that the rate of this happening is extremely low (<1%).   So, my questions are:

1. I reviewed the medical literature it looks like even if resistant isolates are noted in a patient non-resistance can re-emerge and resistance does not usually impact treatment outcome. Is this true?

2. I have had cultures done which are negative. Is there any other way to look for resistance. My doctor said that PCR cannot be done in the lab at my hospital on mucosal lesions. Is there anyone who will do PCR through the mail so that I can be sure that this is HSV-2?

3. It seems like failure to control outbreaks is common from review of the many herpes blogs. Have you noticed this is your experience? Why might this be other than resistance?

4. What can I tell my current partner? We use condoms, but if I am not suppressed then, he isn't getting much protection.

[H. Hunter Handsfield, M.D.]

Welcome to the STD forum.  I'll try to help.

The first and most important thing here is to confirm that you are really having recurrent herpes outbreaks.  Probably you are not, and this is supported by the negative cultures.  You don't say how many cultures were attempted and whether the specimens were collected within 1-2 days of onset of typical lesions.  Although it is true that PCR is more sensitive than culture, most people with true recurrent herpes tested promptly with culture have at least one positive result in several attempts.

The evidence this isn't herpes?  First, a non-herpes explanation is much more common than is HSV resistance to valacyclovir and related drugs.  Resistance is rare and occurs almost exclusively in people with serious underlying immune deficiencies, like AIDS or cancer.  Second, recurrent genital herpes is almost always very limited in its anatomic distribution.  Typically, all episodes recur within an area roughly the size of a quarter or half dollar, i.e. within an inch of each other; and recurrences generally always occur on one side of the body's midline or the other, not both sides.  That is because recurrent outbreaks typically originate in a single spinal nerve root, and nerves do not cross the body's midline.  Third, recurrent outbreaks have rarely if ever been documented to occur more often than every month or so; your frequency of up to twice a month is strongly against herpes.

For these reasons, most of the apparent recurrent episodes -- perhaps all of them -- probably are not due to HSV at all.  To the specific questions:

1,3) True, but probably not relevant to your situation.  When herpes recurs despite suppressive therapy, it is almost always with much less frequency, and each outbreak is less severe and briefer, than in the untreated state.

2) If that particular lab doesn't do PCR testing, probably there is some other lab in the area that does.  The lab should be able to find out where PCR testing is available; or can arrange to send specimens to a reference lab anywhere in the country.  For the reasons above, I am betting that PCR testing also will be negative.

4) See below.

What to do now?  First, it would be good to know how your initial diagnosis of genital herpes was made.  Positive culture or PCR?  Blood test?  What were the initial symptoms like?  Maybe you never had genital herpes at all.  Second, if the initial diagnosis is in doubt, have an HSV blood test now.  If it is negative for HSV-2, it will be further strong evidence against herpes as the cause of your current problem.  Third, ask your doctor about other alternative diagnoses, e.g. folliculitis or some other kind of dermatitits.  If s/he seems uncertain, ask for referral to a dermatologist for a second opinion.  Fourth, if your HSV-2 blood test is positive, follow-up with a PCR test, using the suggestions I made above.  Fifth, if your initial diagnosis of herpes is secure, your partner should be blood tested for HSV.  If you indeed have HSV-2, it will tell whether or not he already is infected, in which case you need not take any precautions at all against transmission, since people are immune to re-catching the HSV type they already are infected with.

Please return with the additional information that I suggested, and I will fine-tune these recommendations accordingly.

Best wishes--  HHH, MD

[kjj122]

Thanks for the information. I just wanted to address some of the questions that you posed..I was diagnosed with HSV-2 by the Herpeselect (IgG) blood test. Unfortunately I do not know my antibody titers. I believe that transmission occurred in May 2007. I first noted symptoms more than one year later in July 2008. At that time I had a lesion on my labia and copious discharge. The lesion never really ulcerated. It just eventually disappeared. I did not take anti-virals with that episode. The next episode occurred shortly thereafter and was characterized by several subcm buttock lesions. Eventually, after several episodes that were prolonged (upwards of 21 days) I started valtrex suppressive therapy. For approximately 2 months I was symptom free. Then it stopped working. Since May of this year I have had frequent outbreaks in a variety of locations as I mentioned previously (definitely crossing the midline) first  on valtrex and then famvir suppression. Of note, I mentioned previously that I developed a buttock lesion on the 23rd. After taking 1000mg twice on the 23rd followed by my regular suppressive doses today, I noted a second buttock lesion in the same vicinity.
So now I am really worried about resistance.

Of note, the cultures were taken from two locations - a lesion on my inner thigh (approximately 3 1/2 days old) and my cervix. Again, they were negative.

I will look for a hospital with PCR testing capability. But could you answer a few more questions -
1. If all of this is herpes and I am an atypical individual with really frequent outbreaks even on suppressive therapy, then when I do not have an outbreak am I more likely than others to shed more often than the norm (someone who has a few outbreaks per year)? I am obviously concerned about transmission with this partner (he is HSV 2-negative) or any others.

2. Does anyone have a hypothesis as to why some people have more frequent outbreaks even while on suppression while others are symptom free? I am concerned that something other than HIV, cancer or immunosuppressive drugs is driving this process.

3. Would stopping all treatment (and refraining from sex) help my body develop a stronger response to anti-viral therapy at this point?

4. Could you recommend a herpes specialist in the Chicagoland area?
Thanks again for your help.

[H. Hunter Handsfield, M.D.]

This further description increases my confidence that you don't have herpes -- or that if you do, it is mostly asymptomatic (as it was for the first year after your blood test and probably before that); i.e. something else is the main cause of your symptoms.  Please do your best to learn the numerical value of your positive HSV-2 blood test.  If you use this forum's search function and enter "HerpeSelect", you will see many discussions about borderline (low) results that are false positive.  If you cannot find that result, you should have another one. Either way, tell me the results and we'll go from there.

Questions 1 and 2:  These issues are likely irrelevant.  Herpes is not the main problem here. Let's address them if and when herpes is actually confirmed.  Question 3:  I strongly suggest you stop treatment.  My prediction is that it will make no difference, because your symptoms are not herpetic.  And in the slight chance I am wrong, your notion is correct:  when people have treatment-resistant HSV, stopping treatment for a few weeks or months often results in renewed effectiveness when it is restarted.

I don't know specific individuals in the Chicago area.  But two possibilities come to mind:  The Chicago health department STD program has some very knowledgeable STD experts who might be able to help, either by offering evaluation at a public STD clinic or by recommending community physicians who understand herpes well; or call any of the academic medical centers (U. of Chicago, Northwestern, etc) and make an appointment in the infectious diseases clinic.

[kjj122]

A related discussion, difficult to control herpes outbreaks continued was started.