TreatmentUpdate59; Vol 7, No. 5 - May 1995
Sean Hosein

In general, most HIV-infected people have decreasing numbers of CD4+ cells over time. Measuring CD4+ (and CD8+) cell counts can be useful because doctors can make decisions about when to begin giving patients drugs to prevent certain infections. By themselves, CD4+ cell counts do not provide a detailed report on the ability of the immune system to resist infections. Many of the life-threatening infections seen in AIDS occur because T cells have lost a very important defense - CMI (cell-mediated immunity). CMI is particularly useful in fighting microbes that can infect and 'hide' inside cells. In such cases, antibodies alone will not be useful and may even help spread the infection. Counting CD4+ cells may provide a sense of certainty; something which people can grasp and easily understand. Performing skin tests may not give people that same sense of precision. Nonetheless, skin testing is one of the few ways to measure CMI.

* WHICH SKIN TESTS?

Nurses injected a small amount of protein from various microbes under the skin. In subjects with normal levels of CMI, within 48 to 72 hours after the injection there is a reaction at the injection site. The reaction is usually swelling and redness and the skin becomes raised. This delayed reaction is why these tests are called DTH (delayed-type hypersensitivity). In subjects who have lost some level of CMI the reaction may be reduced. In subjects with very low levels of CMI there may be no reaction. The immune system of these subjects (no reaction) is described by researchers as 'anergic' or exhausted. If performed over a period of time skin test results can reveal what is happening to the body's ability to produce CMI. For this study, researchers decided that subjects whose skin produced a 10 mm by 10 mm reaction to the injection of protein (from microbes) had a 'positive' reaction.

* STUDY DETAILS

Researchers at military bio-medical centres in the USA have been conducting experiments on HIV-infected subjects. In one experiment researchers conducted extensive laboratory tests on subjects over a five-year period - 1985 to 1990. In this experiment researchers also measured CMI using skin tests. The study doctors analysed data on 600 subjects, 94% of whom were male and 6% female. Their average age was 28 years. At some point during their study 28% of subjects used AZT.

* RESULTS

- about 60% of subjects who had less than 200 CD4+ cells were completely 'anergic'; their level of CMI was extremely low.

- approximately '96% of [subjects] with more than 400 CD4+ cells had [some level of CMI]' These subjects reacted to 'at least one skin test'. These differences in levels of CMI were statistically significant; that is, not likely due to chance alone.

- '86% of subjects with more than 400 CD4+ cells were able to [react] to at least 2 skin tests compared to '45% of subjects' with less than 400 CD4+ cells.

- on average, subjects who could only react to 1 of the 5 proteins (with which they had been injected) had reduced levels of CD4+ cells compared to subjects who had '2 or more [skin reactions]'. Again, this difference was statistically significant. Researchers looked at skin test results and compared them to the appearance of life-threatening infections. They found that subjects who had the following test results developed a life-threatening infection/cancer in the following time:

- no positive tests - 43 months

- 1 positive result - 51 months

- 2 or more positive tests - 55 months

These differences in time to infections/cancers were statistically significant. As well, DTH responses were clearly linked to the development of AIDS even in subjects who had relatively high CD4+ cell counts when they entered the study. Moreover, skin test responses alone could be used to predict which subjects would develop AIDS.

* OTHER GROUPS

Some researchers think that other groups of HIV-infected subjects, such as drug users, may have weaker CMI than (in this study) gay/bisexual men, and that this population may have different skin test results. Other researchers suggest that a smaller measurement (5 mm x 5 mm) could have been used as a cut-off point. In the article below we report results on gay/ bisexual men, drug users (both HIV-infected and non-HIV-infected) as well as heterosexual women.

REFERENCES:

1. Blatt SP, Hendrix CW, Butzin CA, et al. Delayed-type hypersensitivity skin testing predicts progression to AIDS in HIV-infected patients. Annals of Internal Medicine 1993;119(3):177-184.

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Copyright © 1995 - 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