I recently had an exchange with someone who queried me on the blog. Upon reflection, I thought that this was an exchange that should be front and center because it touches upon an important issue.
Although >90% of doctors in the USA would be inclined to put their herpes patients on prophylactic (daily) valtrex, famvir, or acyclovir for life to “keep their herpes symptoms under control,” the ugly truth for me (having some understanding of how the biological system behaves) is that daily antivirals should tend to undercut an infected person’s immunity to the virus hence (1) making them dependent on the antivirals for any type of control and (2) setting them up for a lifetime of higher-than-average symptoms when their antibody response to HSV-1 or HSV-2 crashes after 6 months of daily antiviral treatment.
The exchange is below. The relevant Figure 1 from Gold, et al (1988) is shown above along with Table 1 which conveys that the data shown in the Figure is representative of what happens in most patients. For me, these data highlight the need for an effective therapeutic HSV-2 vaccine.
- Bill H.
This has become the most useful resource I have for understanding how realistically we may one day eradicate herpes, and where to set expectations on therapies. Thank you for taking the time to write.
However, this came as quite a shock: “Prophylactic valtrex is bad medicine that weakens the immune response to HSV, and thus ensures a lifetime of dependence on the drug.” I want to be clear about what you mean as I take the prescribed daily 500mg to presumably suppress outbreaks (I have had none since taking it, but have had hsv for <1 year). Do you mean the therapeutic/daily use of the drug? Or are you referring to those who might think taking it will prevent acquiring hsv? Can you please elaborate? Obviously this would not be great news for the many of us who take valtrex on advice from our doctors.
I should note that from a laymen’s perspective the logic seems to make sense. If you suppress the virus, the immune system will take it “less seriously.” I have no idea if that has any basis in medicine. Thinking along those lines when I had my initial outbreak, I attempted to do some research to determine if taking Valtrex immediately after acquiring hsv may decrease your immune response in the long run. I found a few studies that seemed to indicate no difference but I’m interested in any insight you have on these matters.
Please forgive my delayed response to this important question. First off, please allow me to point you to the raw data. The relevant studies of which I am aware were both published in 1988 and should have been a red flag to everyone that prophylactic antiviral drugs were problematic. The relevant studies are:
1. Gold D, Ashley R, Solberg G, Abbo H, Corey L. 1988. Chronic-dose acyclovir to suppress frequently recurring genital herpes simplex virus infection: effect on antibody response to herpes simplex virus type 2 proteins. J Infect Dis. 158:1227-34. http://www.ncbi.nlm.nih.gov/pubmed/2848900
To Read Paper, click link below….
2. Erlich KS, Hauer L, Mills J. 1988. Effects of long-term acyclovir chemosuppression on serum IgG antibody to herpes simplex virus. J Med Virol. 26:33-9. http://www.ncbi.nlm.nih.gov/pubmed/3183633
To Read Paper, click link below….
What the study of Gold, et al (1988) convincingly showed was that patients who go on prophylactic acyclovir (and presumably valtrex or famvir) experience a significant decrease in their antibody response to HSV-2. At the time, this should have raised concerns about whether or not the prophylactic drugs erode the body’s natural ability to combat HSV-2 infection. In particular, if one reads the study of Gold, et al (1988), Figure 1 demonstrates that patients taking daily acyclovir for 6 or 12 months exhibit a marked decrease in their antibody response to HSV-2 proteins. In contrast, patients taking a placebo for 6 or 12 months show a steady level of antibody to HSV-2, which remains constant over time because subclinical and/or symptomatic HSV-2 reactivation events keep the immune system engaged such that HSV-2-specific B cells remain stimulated to produce HSV-2-specific antibodies at a rate that is in balance with the natural decay rate of antibodies (i.e., half-life = 21 days). The results are convincing, and are consistent with how the biological systems that are “persistent infections” generally behave.
Recently, it has become more apparent that HSV-specific antibodies play a critical role in rapid immune control of HSV-1 and HSV-2 infections (Halford, et al, 2015; Royer, et al., 2016; Iijima and Iwasaki, 2016).
Halford WP, Geltz J, Messer RJ, Hasenkrug KJ. 2015. Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2. PLoS One. 2015 10:e0145228 http://www.ncbi.nlm.nih.gov/pubmed/26670699
Royer DJ, Gurung HR, Jinkins JK, Geltz JJ, Wu JL, Halford WP, Carr DJ. 2016. A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity. J Virol. 90:5514-29 http://www.ncbi.nlm.nih.gov/pubmed/27030264
Iijima and Iwasaki. 2016. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature. 533:552-6. http://www.ncbi.nlm.nih.gov/pubmed/27225131
Therefore, any prophylactic antiviral drug regimen that reduces the antibody response to HSV-1 or HSV-2 should make people’s immune systems less competent to control HSV infection, and thus increasingly vulnerable to more frequent outbreaks and/or nerve pain (caused by a non-protective immune response to subclinical HSV reactivation in the ganglia).
The study of Erlich, et al (1988) offers a parallel conclusion. Therefore, it is possible that the most responsible way for patients to use valtrex or acyclovir is by episodically taking these drugs as needed to curb the duration of outbreaks so that their body’s immune system might learn to fight the virus better in the in-between times when they are not having full-blown outbreaks.
Against that background, Rational Vaccines (http://rationalvaccines.com/) is proposing that an effective therapeutic HSV-2 vaccine might completely eliminate the need for antiviral drugs such as valacyclovir, famvir, and acyclovir, which suffer from the serious limitations of (1) poor solubility / absorption from the intestines to the bloodstream (i.e., poor bioavailability) and (2) failure to meaningfully limit HSV shedding to the point where HSV transmission rates are curbed and decrease over time. If these drugs actually worked well, then the herpes problem should have started dissipating in the year 2000. That is, if antiviral drugs were highly effective at controlling HSV replication, then HSV shedding and transmission rates should have decreased precipitously when these drugs became widely available. However, on all fronts, current antiviral drugs against HSV are marginally effective, and thus here we are in the year 2016 with over one million people per week continuing to be newly infected with HSV-1 or HSV-2.
A therapeutic HSV vaccine regimen that actually works for patients, combined with effective prophylactic HSV vaccines, represent real medicine that will be sufficient to end the silent herpes epidemic once and for all.
- Bill H.