Reflections

2014 Report on Conversations With Top HSV Researchers Terri Warren, R.N. and Lawrence Corey, M.D.

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In August 2014, Cat and co-National HELP administrator Auburn G. Locks again met with two of the herpes community’s top researchers, Terri Warren of Portland’s Westover Height’s Clinic and Dr. Lawrence Corey of the Virology Research Center at the University of Washington. In addition, Terri Warren held a 90-minute Q&A session at the Portland National Event. The goal for Auburn and me was to find out what was new, or needed confirmation, in our ongoing investigation of the behavior of the herpes simplex virus (HSV), the virus that causes our herpes outbreaks. Quite a bit of material we collected involved vaccine research news and methodology, as well as testing and treatment for HSV.

As before, we are extremely moved and grateful for the time that these two highly-regarded medical professionals of our H community have generously given us.

What follows is a report on these conversations.


What is going on in the arena of HSV treatment research?

It might be useful to first identify three types of treatments that are often discussed in our community:

  • Curative treatments eradicate existing virus from the body.
  • Prophylactic treatments prevent the body from contracting virus.
  • Therapeutic treatments treat existing virus in the attempt to reduce their activity. In the case of HSV, these vaccines attempt to reduce recurrences, was well as hopefully reduce viral shedding and ultimately transmission to uninfected partners.

Curative treatments
At the moment there are no curative vaccines or medicines available, and as far as the researchers know, none are in clinical trials.

Prophylactic treatments
As in the case of the curatives, there are no prophylactic vaccines either available or in clinical trials in the U.S.. Terri reported that her clinic, Westover Heights—one of the primary sites in the country continuously involved in studies on HSV—has been involved in five prophylactic vaccine trials in the last 30 years, but “all have failed.” [1]

Though it would seem intuitive that the existence of vaccines against shingles and chickenpox would also make an HSV vaccine not only possible but probable, Terri stated that “that technology doesn’t appear to be the technology that works for herpes simplex virus. Though they’re in the same family, they don’t share a ton of characteristics. So people often ask if it would be helpful to get the shingles vaccine for their genital herpes, but it doesn’t make a difference.”

Terri did mention that one of the U.S. companies developing a therapeutic vaccine is considering a move into the prophylactic vaccine arena, but didn’t name the company. Nonetheless, this was somewhat good news. She also noted that Dr. Ian Frazer, who pioneered the technology that developed the first HPV vaccine, is currently involved in Australian biotech Admedus’ studies on a DNA-based therapeutic vaccine designed to also have prophylactic benefits, preventing new infections. This vaccine passed the Phase I safety trials in Australia early last year and was slated to begin Phase 2 trials by the end of 2014.

Therapeutic treatments
Terri reported that her clinic is involved in clinical trials of therapeutic vaccines from three pharmaceutical companies, Vical, Genocea and Agenus. The Vical vaccine is still in Phase 1 trials, which primarily look for side effects and safety issues. The Genocea vaccine, has entered Phase 2 during which the study will test the efficacy of different doses of the vaccine, in order to find the best dosage to achieve an acceptable reduction in viral shedding. This phase will likely continue for at least a year before results can be reported. The Agenus vaccine completed its Phase 2 trials, reporting only a weak reduction in viral shedding.

Several other preliminary studies are underway in various places throughout the country. The University of Washington is currently investigating CD8 cell activity and behavior, aiming for a better understanding of its potential role in vaccine development.

Terri described the timeline of clinical trials as requiring three phases before applying for FDA approval, with most vaccines discontinuing trials after the first or second phase. “Phase 3 trials are really big,” she told us. “There’ll be a lot of patients enrolled in a lot of different sites if it gets to that,” and Phase 3 trials can take 2-3 years to complete. Some vaccines move on to Phase 4 trials after the drug is marketed.

The enrollment period may be over for these active trials, but that information—and information about other clinical trials—can be found at the National Institute of Health’s (NIH) Clinical Trials pages by searching for the name of the company and the term “HSV” (for example by typing “Genocea HSV” into the search field.)

Terri also mentioned a therapeutic oral medicine called Pritelivir, developed by a German company called AiCuris, which managed to achieve a very significant reduction in shedding during trials, knocking down the percentage of shedding days from 11-20% down to about 2.7%. [2] [3] [4] Unfortunately, a concern arose over some data from primate (monkey) trials that was released, and the trials have now been put on hold. Terri is not sure when, or whether, these trials will start again.

We asked Dr. Corey whether he had any overarching message to the HSV community, and he responded somewhat passionately with some thought-provoking words—that we as a community must lobby both the pharmaceutical companies and the government agencies to support research for better treatments and remedies, and to support promising studies that may lead to prophylactic or curative solutions against HSV. One thing we know is that the current thinking of these organizations is that herpes, as a primarily non-fatal condition, is a lower priority than other STDs. However—besides the sometimes emotionally debilitating societal stigma that surrounds the virus—confirmed cases of neonatal herpes in infants; the rising incidence of genital HSV-1 in teens and adults (Terri stated that 40-50% of new genital herpes cases are due to HSV-1); and other serious, though rare, complications arising from HSV in the system, should be impetus to find better solutions.

Have there been studies that take into consideration various triggers, such as the arginine-lysine connection?

Terri cautioned that the evidence regarding lysine and arginine’s effect on HSV is only in vitro evidence. Arginine may excite the virus in a laboratory, but there is no scientific support for its effect on the virus in humans. She cited 15-20 studies that have been conducted just on lysine’s effectiveness against the virus in humans, none of which were conclusive, and in many of which “the meta-analysis of lysine did not show a statistical benefit over … placebo.” This means that the patients who got lysine did not show more of a reduction in outbreaks and shedding than those who got the placebo. She additionally cautioned that not all studies that are conducted on various remedies are of a high quality.

Terri did say, however that she didn’t see any reason not to take Lysine if indeed folks felt that they were getting a benefit from the supplement, but she cautioned that very often people can become biased toward a particular remedy just because they’ve heard so much about it, in their search for remedies that work, rather than having any scientific evidence of its efficacy. In the end, if there were a choice between spending money on a supplement which was unproven as a treatment for HSV or an antiviral with decades of science behind its efficacy, she would encourage going with the sure thing. For those in financial straits, acyclovir can be purchased without insurance at a very discounted rate, at certain pharmacies chains, including those at Target and Walmart, as well as Walgreens and Costco.

With regard to other triggers, only one has basis in scientific fact. In a 1985 study at the University of Utah, ultraviolet light, such as that from the sun, was “proven without a doubt” to trigger an oral HSV-1 outbreak in humans. [5]

Terri also described cases of patients who had outbreaks triggered by chemotherapy. Since this procedure detracts from the immune response of a patient, it would seem to confirm that anything that compromises our immunity could trigger outbreaks. It follows that activities that reduce stress, such as yoga and meditation, which may boost the immune function, could help us avoid outbreaks.

What do the numbers mean on my IgG test result?

The “number” on the IgG test result is called the “index value.” Directly following a primary infection—the first time that a patient has ever contracted any type of HSV—the IgG index value may be very low, since the test looks for antibody in the blood. Antibodies do not generate until the virus is first introduced to the body, and may not have generated enough to trigger a positive index value for the virus for the first several weeks. It can take up to 16 weeks to have a definitive positive result.

The standard index for the IgG usually consists of these values:

  • 0.0-0.9 – negative
  • 0.9-1.1 – inconclusive
  • 1.1+ – positive

Low Positivesan index value between 1.1 and 3.5, however, is generally considered to be a low positive, and will require a confirmatory test 4-6 months following the sexual event that caused the primary infection. The test most recommended to confirm an HSV diagnosis is the Western Blot, administered by the University of Washington, and available via the UW Virology Research Center’s FAQ page.

Changing IgG numbers – this information was new to us: the IgG index values do rise until sometime around or slightly after the antibodies generate an accurate positive result. At that point, the antibody volume “levels off” according to Terri. Dr. Corey confirmed that the antibody count “plateaus” after a period, following a positive result.

However, it still appears to us, having heard multiple results from our almost 5,000 members at National HELP, that the IgG index values continue to rise over the years in some cases, and in other cases fluctuate quite a bit. According to both Terri Warren and Dr. Corey, these changes have more to do with laboratory methods—specifically varying controls at different labs, against which these index values are measured—than rising, falling or fluctuating antibody counts. The antibody counts do not fluctuate and therefore do not cause fluctuating index values from test to test.

What does it mean when my doctor says I’ve been “exposed” to HSV?

This term is the most misused and misunderstood term in herpes diagnosis. An accurate positive result on a reliable blood test means you have contracted the virus. There is no situation in which such a result only indicates exposure, but not transmission. Terri equates this kind of misleading statement to saying that a positive pregnancy test means “you’ve been exposed to semen.” Just as a positive pregnancy test means you are pregnant, an accurate positive on an HSV test means “you’re infected and you’re infectious to others.”

What is the difference between “types” and “strains” of HSV?

These two terms mean two different things:

  • Type – the herpes simplex virus (HSV) features two distinct types: HSV-1 and HSV-2.
  • Strain – each of the two types of HSV has been found to consist of several different strains

Terri finds differentiating between the two types of HSV to be important, because some of the properties and behavior of each are different. She confirmed the understanding that HSV-2 antibodies protect against contracting HSV-1, but also confirmed that the reverse is not true.

However, she does not find differentiating between the various strains within the same type to be important. For one thing, she is sure no doctor will bother to determine whether someone has strain A or B of an HSV type, unless it involves a legal imperative to genetically fingerprint the viral DNA, as in cases of child molestation.

Terri cited that one old study showed that 1 in 55 patients tested had more than one strain of a single HSV type (that’s less than 2% of us). This was a concern during a time when researchers thought that some strains might be more virulent than others. However, what clinical experience has found in three decades is that HSV+ people who have sexual relationships with other people who have the same type of HSV do not change their recurrence (outbreak) pattern much at all. Therefore HSV clinicians “don’t advise people who are known to have the same type to be concerned about transmission in a relationship with someone that has the same type,” out of fear of catching a different strain. In other words, even if it were possible that one can contract an entirely different strain of the same HSV type, it appears, from 30 years of clinical experience, that doing so would not make a noticeable impact on the pattern or frequency of our outbreaks.

Finally, Terri posits that patients mounts enough of an immune response—not just utilizing antibody but also T-1 responses—that “make it unlikely that they would contract a new strain of the same virus.”

Are there internet resources that you recommend as reliable for medical information and for online testing?

Terri feels the American Sexual Health Association (ASHA), an STD information and advocacy organization with a 100-year-old reputation for excellence, “should be the number one resource,” for information about HSV and other STDs, citing their “very good, reliable information about herpes.”

Terri cites Health Check USA as her go-to online testing resource. She recommends purchasing IgG testing kits from online testing merchants when our doctors refuse to give us the blood tests that could help us diagnose our or our partners’ HSV status. The procedure involves filling out an online form, receiving a lab request form to take to a patient draw station, where your blood is drawn. You would then receive the results online.

How often do we shed (give off) HSV virus on the skin?

Terri cited recent studies that found that we shed between 12-15% of days. She furthermore told us that even on suppressive (daily) antiviral therapy, we can still shed about 7% of days.

There is an official statistic that cites 1-3% of days as the percentage that oral HSV-2 sheds. Terri clarified that 3% of days is the amount that HIV patients shed, and that for immunocompetent people (folks with normal immune function) the percentage is 1%. HSV-2 rarely sheds from the mouth in almost all people, with rare exceptions.

Is there a link between bacterial vaginosis (BV) and HSV?

Bacterial vaginosis (BV) is an infection of the vagina caused by bacteria. Both Terri and Dr. Corey confirmed that from both clinical experience and research, there appears to be a link between the two conditions. Terri cited changes in the flora of the female genitalia as a probable reason for the correlation. Studies on the correlation between the two conditions were published in the Oxford Journal of Clinical Infectious Diseases by the University of Pittsburgh in 2003 [6] and the University of Washington in 2014 [7].


1. Johnston, C., Koelle D.M., Wald A. Current status and prospects for development of an HSV vaccine. Vaccine (Elsevier). 2013. PDF.

2. Wald, A., Corey, L., Timmler, B., Magaret, A., Warren, T., Tyring, S., Johnston, C., Kriesel, J., Fife, K., Galitz, L., Stoelben, S. Huang, M.L., Selke, S., Stobernack, H.P., Ruebsamen-Schaeff, H., Birkmann, A Helicase–primase inhibitor Pritelivir for HSV-2 infection. New England Journal of Medicine. January 2014. Web.

3. “Promise for a New HSV Treatment Option?” The Helper (ASHA). Web.

4. Birkmann, A., McCormick, D., Kropeit, D., Timmler, B., Stoelben, S., Wald, A., Field H., Richard, M.P., Zimmermann, H., Rübsamen-Schaeff, H.. Excellent efficacy of Pritelivir (AIC316) in suppression of genital herpes, a novel drug against herpes simplex virus (HSV) type 1 and 2. Sexually Transmitted Infections (BMJ). July 2013. PDF.

5. Spruance, S.L. Pathogenesis of herpes simplex labialis: experimental induction of lesions with UV light. Journal of Clinical Microbiology. September 1985. PDF.

6. Cherpes T.L.., Meyn, L.A., Krohn, M.A., Lurie, J.G., Hillier, S.L. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Journal of Infectious Diseases. August, 2003. Web.

7. Masese, L., Baeten, J.M., Richardson, B.A., Bukusi, E., John-Stewart, G., Jaoko, W., Shafi, J., Kiarie, J., McClelland, R.S. Incident herpes simplex virus type 2 infection increases the risk of subsequent episodes of bacterial vaginosis. Journal of Infectious Diseases. April, 2014. Web.

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