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Acyclovir -- One Reason Why I'm Still Alive?

| 9 Comments

ZoviraxI believe I was coinfected with HIV and genital herpes in August, 1983. There was no HIV test back then (they hadn't discovered the virus yet), and the herpes virus was the one making all the headlines and scary magazine covers. I was diagnosed with it after my first outbreak. Thankfully, a drug had come to market the year before to help treat these outbreaks. It was an ointment called Zovirax (acyclovir), and I used it often.

In January, 1985, they approved an oral version of Zovirax, and I quickly switched to that. Later that year, I was finally diagnosed as HIV positive (they only discovered the virus the year before).

I don't remember exactly when I started taking oral acyclovir every day, but my doctor and I had heard it was being studied that way to prevent outbreaks. So sometime before the first anti-HIV drug was approved (AZT, March, 1987), I fortuitously started popping daily acyclovir. I've been doing so ever since.

[Coincidentally, both acyclovir and AZT were developed by Burroughs Wellcome, now called GlaxoSmithKline.]

According to an NIH study released on Wednesday, I was probably taking a drug that not only prevented herpes outbreaks, but also hindered the HIV that was battling my immune system. Acyclovir might be one of the reasons I'm alive today.

Here's the fascinating study:

Herpes Virus Changes Anti-Herpes Drug to Form that Hinders AIDS Virus

The drug acyclovir has long been used to suppress outbreaks of oral and genital herpes. Herpes viruses change acyclovir to a form that prevents them from reproducing.

Now, it appears that after acyclovir is altered by herpes viruses, it also interferes with the AIDS virus’s ability to reproduce, report researchers from the National Institutes of Health and other institutions.

The study, conducted in cultures of human lymphatic tissue, was published online in Cell Host & Microbe.

"The findings open up promising new avenues of investigation in the fight against the AIDS virus," said Duane Alexander, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute where much of the research was conducted.

The study’s lead authors were Andrea Lisco and Christophe Vanpouille, of the NICHD. Other authors of the study were from McGill University, Montreal; the University of California, Los Angeles; Emory University School of Medicine at the Veterans Affairs Medical Center, Decatur, Ga; St. George’s University of London; Katholieke Universiteit Leuven, Belgium; Cardiff University, Wales, and the National Cancer Institute, also at the NIH.

The most well known herpes viruses, herpes simplex virus-1 and herpes simplex virus-2, cause cold sores and genital herpes, respectively. Several other herpes viruses, however, are believed to be benign and don’t cause any symptoms in adults, explained the study’s senior author, Leonid Margolis, M.D., Ph.D., head of NICHD’s Section on Intercellular Interactions. These benign viruses are so widespread that most people probably harbor one type or another and don’t realize it.

On the basis of his experiments, it’s reasonable to assume that most of these viruses have the ability to alter acyclovir so that it hinders HIV, Dr. Margolis said. Although it will take additional studies to confirm, Dr. Margolis added, the results of this study suggest that acyclovir might make a useful addition to the cocktail of drugs used to suppress HIV in people infected with both HIV and one of the many forms of herpes virus. Another prospect for future research would be to chemically modify acyclovir in the same way that herpes viruses do, an avenue which is currently under investigation.

The researchers began their study by culturing HIV and herpes simplex virus-2 together in tonsils removed during surgical procedures. The tonsil tissue provides an environment similar to the body and allows the viruses to reproduce much like they would during an infection.

Early studies of cell cultures failed to show that acyclovir had any effect on HIV, Dr. Margolis said. Yet other studies had shown reductions in HIV levels when people with both HIV and herpes simplex virus-2 (HSV-2) were treated with acyclovir.

When the researchers added acyclovir to the cultures, the levels of both HIV and HSV-2 fell. Next, the researchers grew HIV in tonsil cultures that were not infected with HSV-2. Surprisingly, when they added acyclovir to the HSV-2 free cultures, the levels of HIV in these cultures also dropped. But testing revealed that although the tonsil tissue cultures were free of HSV-2, they had been infected with other kinds of herpes viruses, presumably long before the tonsils were removed surgically.

The researchers took additional steps to avoid mixing HIV with any herpes viruses. They next added HIV to cultures of T-cells (a type of immune cell) that were free of herpes viruses. When the researchers added acyclovir to the T-cell cultures, the levels of HIV in the cultures where unchanged. Similarly, acyclovir did not alter HIV levels in tonsil tissue in which herpes viruses could not be detected.

Dr. Margolis explained that when acyclovir is taken up by a cell infected with herpes viruses, the virus chemically alters the drug, adding a chemical compound called a phosphate group. The chemically altered, or phosphorylated, acyclovir interferes with the herpes virus’ ability to reproduce, he said.

The experiments with tonsil tissue strongly suggested that the phosphorylated form of acyclovir also hindered the reproduction of HIV, the study authors wrote.

Next, the researchers tested a phosphorylated version of acyclovir against reverse transcriptase, the molecule that HIV uses to reproduce. The genetic material of HIV is composed of RNA (ribonucleic acid). When it infects a cell, it uses reverse transcriptase to translate the information in its RNA into DNA (deoxyribonucleic acid), which it then incorporates into the DNA of the host cell. The researchers found that the phosphorylated acyclovir prevented reverse transcriptase from producing DNA.

Other authors of the study were Egor P. Tchesnokov, Jean-Charles Grivel, Angélique Biancotto, Beda Brichacek, Julie Elliott, Emilie Fromentin, Robin Shattock, Peter Anton, Robert Gorelick, Jan Balzarini, Christopher McGuigan, Marco Derudas, Matthias Götte, and Raymond F. Schinazi. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.



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Comments on Peter Staley's blog entry "Acyclovir -- One Reason Why I'm Still Alive?"

Hey Peter, you beat me to it! I was going to blog about the same study. I've already linked Aidsmap's version in a thread in the forum.

http://www.aidsmap.com/en/news/AE968E37-6F05-4F0F-8FB9-E3A7C39CA15F.asp

As you know, I'm not on ARVs yet. When I finally started acyclovir prophylactic, it seemed to me that my CD4 counts improved. Maybe there was a connection and it wasn't just my imagination.

Also, the Aidsmap report on this study also mentions that men who are on acyclovir tend to have a smaller concentration of hiv in their semen. Interesting stuff!

Ann

Taking what probably seem like a bit of a drunken lurch in a somewhat different direction ...

I have always wondered why no-one in Hollywood has ever made a film about Henry Wellcome - the founder of Burroughs Wellcome – because his story has always seemed to me to have all the ingredients of the sort of film they once loved to make: the story of how a child born in a frontier cabin, in Wisconsin, grows up and moves to London, marries the daughter of a philanthropist who saved 60,000 orphans from the streets, founds a company, finds fame and fortune, becomes an Honorary Fellow of the Royal College of Surgeons, gets knighted by the King of England, dies and endows all of his entire wealth and company to a charitable biomedical research trust .. under whose stewardship the company goes on to develop a drugs which give hope to millions.

From his death (in 1936) until 1986, Burroughs Wellcome was run entirely for the benefit of the Wellcome Trust (and later also the Burroughs Wellcome Fund). The trust still owned most of the company until 1995 and is today worth more $30 billion and investing well over $1 billion a year in medical research.

Add in the bits about the troubled marriage, the rejected child sent to live with foster parents, his wife's affairs with the likes of Somerset Maugham and the scandal of the divorce .. and you could even make a film worthy of this century.

For some strange reason, many people seem to think that philanthropy on the mind boggling scale started with Howard Hughes and Bill & Melinda Gates.

Peter,

Interesting post. I, too, took acyclovir for years, starting with an outbreak of shingles in September of 1985, and have always felt that it was an important part of my HIV treatment strategy. Nathaniel Pier, my doctor in the mid-80s, described acyclovir as effective at "lowering the overall viral playing field" and therefore minimizing potential risks for aggravation of HIV.

Sean

Interesting Peter. I was diagnosed in 1986 and have been on and off various anti viral medications since then. However, I too was diagnosed with herpes simplex and given the zovirax ointment which I used daily. I continued taking the pills - even on occasions when I went on an anti-viral holiday. I continue as a long term survivor.
Tom

Great news!Like you Peter I was diagnosed very early; in october 85 actually. I did not take any meds until 1994 but at that time my health was getting worse. One day I met my doctor on the street and I had a bad case of cold sore. He recommended I took Acyclovir daily as he said the herpes virus is weakening your immune system...which of course is not good. I have been taking Acyclovir since december 94, non stop twice daily. Whereas many other HIV-poz are not taking it I was tempted not to stop take it...but here I am almost 23 years after the diagnostic, still healthy...even if I am now taking loads of anti HIV drugs...I am convonced that Acyclovir has played a role in my survival.

Because of your blog, the subsequent POZ article and a recent outbreak, I've decided to go back on acyclovir which I used for a spell then decided to use only prophylactically. I got it in my head that I didn't want to use drugs if I could avoid them. Interestingly, it was the herpes virus that gave me the first and only clues something was wrong with me several months after seroconversion. I had a series of outbreaks whereas the first and only, unconfirmed outbreak had been 2 years prior while caring for my s.o. dying of cancer. Stress-induced. A couple of days ago, I started back on a daily regimen and will look for a possible impact on CD4 count. It is the single, most noticeable change in my physiology post-dx---an uncanny vulnerability to outbreaks and almost always attached to stressful incidents. Thanks so much for posting your experience. Reading all of the recent e-ink changed my ego-driven thinking--here it may be doubly therapeutic!

I was diagnosed as HIV+ in 1991. I was also diagnosed with genital herpes in the same year. My doctor put me on 800mg one per day of acyclovir. I have maintained that dosage since. I take a cocktail as well. I remain undectable and otherwise in good health. I too attribute my longevity in part to the acyclovir along with two multivitamins per day.
Terry K.

Peter, I'm just glad you're still alive. I admire your work and clarity of thought. Persevere.

I'm a 43yo HIV+ white gay male and I've had Simplex 1 since I was a child. I've always gotten fever blisters on my lips and was taking Zovirax as soon as it was available, long before my seroconversion.

I am very fortunate: with the exception of 6 months of chemotherapy (8/99-4/2000) I have never in my life taken HIV/AIDS drugs and to date remain healthy. Never occurred to me but acyclovir may be part of the reason for this.

Forgot to mention I got my positive test result in August 1993. I was probably exposed 6-12 months prior to that.

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This page contains a single entry by Peter Staley published on September 13, 2008 10:50 AM.

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