Imiquimod and drug resistant herpes simplex
1 October 2001. Related: Coinfections and complications.
Infection with herpes viruses can cause sores and, in some cases, ulcers in the mouths and genitals of people. These sores can usually be treated with antiviral drugs such as acyclovir (Zovirax), Valtrex (valacyclovir) or Famvir (famciclovir).
Unfortunately, cases of herpes that are resistant to these drugs are increasingly leaving doctors and their patients with few options. However, a group of doctors in New York recently reported the case of a person with AIDS who successfully recovered from drug-resistant herpes when he was treated with the immune booster imiquimod (Aldara).
The doctors provided details on a 34-year-old man whose CD4+ count was 200 cells and whose viral load was “undetectable.” He had been taking highly active antiretroviral therapy (HAART) for about a year and had symptoms of herpes on his genitals for about five months. Doctors prescribed the following regimens one at a time to treat the herpes infection:
acyclovir – 1, 200 mg/day for one month
Valtrex – 2 grams/day for one month
Famvir – 1, 500 mg/day for one month
Because these drugs did not help, doctors then prescribed 5% imiquimod cream, which the man applied to his lesions and then washed off eight hours later. He did this three times in one week and then stopped the drug.
After four days, the pain from the herpes infection cleared. After one week, the lesions healed. The man has remained free from herpes lesions for at least one month and did not report any side effects associated with Aldara.
Imiquimod is licensed in Europe for the treatment of warts on the genitals and anus. This drug appears to work by stimulating CD8+ cells and other cells of the immune system in the skin to fight viral infections. The drug is currently being investigated for the treatment of certain types of skin cancer. It has also been used to treat another troublesome AIDS-related complication – mollusca lesions – caused by MCV (Mollusca contagiosum virus). Further research on imiquimod, and possibly more effective immune boosters such as resiquimod, is underway.
Imiquimod can cause skin irritation, rash and itching, among other side effects. Doctors are not sure if the drug will work for people with HIV/AIDS who have very low CD4+ counts. The team of doctors in New York suggests that imiquimod be tested in clinical trials to confirm its anti-herpes activity.
Comment
A related compound, resiquimod, is an the results of a Phase II clinical study with resiquimod (a more potent analogue of imiquimod) were presented in September, 2000 at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The results of this blinded, dose ranging study in patients with frequently recurring genital herpes showed time to first recurrence extended approximately 3 times (resiquimod gel 169 days compared to vehicle 57 days) and proportion of patients without a genital herpes recurrence in 6 months increased approximately 4 times (resiquimod gel 32% compared to vehicle 6%).
Phase III studies with resiquimod (R-848) are under way in North America and Europe. If these Phase III trials proceed on track, 3M Pharmaceuticals expects to file licensing dossiers for this new molecule globally in Q2 2004. The first launch for this new molecule could be as early as Q2 2005 in the United States. Other launches would proceed globally based on individual country registration and reimbursement feedback to 3M Pharmaceuticals.
Both imiquimod and resiquimod are hypothesised to work by stimulating local production of interferons leading to autovaccination of HSV.
Reference:
Gilbert J et al. Topical imiquimod for acyclovir-unresponsive herpes simplex virus 2 infection. Archives of Dermatology 2001;137:1015-1017.
http://www.ncbi.nlm.nih.gov/pubmed/11493093?dopt=Abstract
Source: CATIE News.
CATIE-News is written by Sean Hosein, with the collaboration of other members of the Canadian AIDS Treatment Information Exchange, in Toronto. From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE’s Information Network at http://www.catie.ca/