TreatmentUpdate43: Vol. 4, No. 3, July, 1993
Sean Hosein

Researchers at the University of California at San Francisco and at the California Pacific Medical Centre (also in San Francisco) have recently had the results of their experiments on humans published. Twenty subjects infected with HIV were recruited for this study. At the start, the average CD4+ count was 347 cells (counts ranged from 100 to 600 CD4t cells). Sixteen subjects had no symptoms and the remaining 4 subjects had persistently swollen lymph nodes. Nine subjects were taking AZT before the study began and they continued to use that drug at the same dose during the trial. Subjects who had life-threatening infections and/or cancers were not allowed to enter the study. Overall, subjects were observed for an average of 12 months, others for as long as 20 months. Two subjects left the study; one because of "cosmetic effects" and the other because he was encouraged by his family doctor to leave. These two subjects continued to be monitored and used as "controls".

DNCB Protocol--Part 1

DNCB was dissolved into a solution of acetone. Subjects were given solutions of DNCB in various concentrations (10%, 2%, 0.2% and 0.02%). A small amount of 10% DNCB solution was put on a 25-millimetre patch of skin "usually on the forearm." Over the next 3 days swelling and redness at this site should have occurred. If this did not happen subjects "repeated this dose at weekly intervals until sensitization [redness, swelling, itching] occurred."

DNCB Protocol--Part 2

Once this sensitization happened subjects were supposed to put some of the 2% DNCB solution on a another patch of skin (25 mm) on the "forearm or upper arm" once per week. As subjects continued in the trial the site where DNCB was first placed would swell turning red or itching (this reaction is described as a "reflare"). According to the researchers involved with the study this reflare confirmed that the immune system had been "sensitized" to DNCB. Once this happened subjects were told to decrease the weekly dose of DNCB to the weakest concentration that caused this reaction.

Results--CD4+ Cells

Before the use of DNCB the average CD4+ count was 347 cells. After use of DNCB the count was 343 cells. This change was not statistically significant and the CD4+ counts were considered stable. There were no statistically significant differences in CD4+ cells between those on AZT and others not using AZT in this study. Results--CD8+ Cells

Before using DNCB the average CD8+ cell count was 904 cells. After becoming sensitized to DNCB the CD8+ count increased to 1068 cells. This increase was statistically significant. This increase happened whether or not subjects used AZT. Over the first 6 months of the study the increase in CD8+ cells continued. Please see the section D for how DNCB works.

Results--NK Cells

NK (natural killer) cells are important in cancer control and can perform anti-viral activities. Increases in NK cells from an average of 95 cells to 119 cells were noted. This increase was statistically significant and happened in subjects whether or not they used AZT.

Results--Symptoms

No subject developed a life-threatening infection and/or cancer during the study.

Results--HIV Replication

Using quantitative PCR (polymerase chain reaction), tests were done to measure the amount of the HIV enzyme RT (reverse transcriptase) in the lymphocytes of 11 subjects. In 9 subjects using DNCB there was a significant decline in the amount of this HIV enzyme while in the 2 control subjects the amount of HIV in their lymphocytes increased.

Results--Side Effects

DNCB exposure was described as "safe" by the study doctors; no subjects experienced any life-threatening reactions. In 2 subjects "burning, itching and [inflammation and redness]" occurred during the study. Over a period of 2 days this reaction went away. According to the study doctors, "most subjects experienced some initial discomfort at the application site."

Trial Summary

DNCB is known to improve some immunofunctions. Applying a solution of this drug to the skin appears to have an effect on the whole immune system. Cells of the immune system in the skin which are "exposed to DNCB" are thought to stimulate CD8+ and NK cells. Both types of cells can have anti-viral activity. CD8+ cells can produce an anti-viral substance (researchers are not certain just what this substance is) which may explain the decrease in the amount of HIV in the lymphocytes of DNCB-treated subjects. Use of DNCB may stabilize the decline of immunofunctions in some people with HIV infection. Interestingly, DNCB stimulation of the immune system did not cause the CD4+ cell count to decrease significantly. PCR tests suggested that HIV production either remained constant or fell to a low level as a result of DNCB use. References are at the end of section D.

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Copyright © 1993 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca