Canadian AIDS Treatment Information Exchange (CATIE) TreatmentUpdate48, Vol. 4, No. 8 - March 1994
Sean Hosein

In their latest report, the researchers presented results on 20 subjects- 3 from the original pilot study and 17 new subjects. All subjects were in the study for at least 6 months and some as many as 29 months. Fifteen subjects were male and 5 female. No subject was using AZT nor had any life-threatening infections/cancers or used preventative doses of antibiotics to prevent such infections. Subjects had symptoms such as: at least 2 persistently swollen lymph nodes, "intermittent or continuous fever for more than one monthly repeated night sweats", unintentional weight loss, a decrease in their CD4+ cells. Blood was taken at regular intervals for extensive laboratory tests. Every six months nurses injected small amounts of purified proteins from yeasts, tuberculosis-causing bacteria and other microorganisms under the skin of subjects to see if their immune systems could respond. This type of reaction is called DTH and is explained in the 'Results' section. The researchers gave the subjects MOP in a dose of 0.4 to 0.6 mg/kilogram of body weight to swallow 2 hours before their blood was exposed to UV light. Subjects had this procedure once each month.

RESULTS--LIFE THREATENING INFECTIONS

Three subjects did not always get their monthly EP. One of these subjects did not confess that he had the life-threatening diarrhea commonly called "crypto" before entering the study. Four months after enrolling in this study he developed the life-threatening pneumonia PCP. Another subject also developed PCP after being in the study for six months. According to the researchers, both of these subjects had a "simultaneous rapid decline in their [percentage of] CD4+ cells." Treated with Bactrim/Septra they both recovered and resumed receiving EP. One of these two subjects left the study. The researchers did not explain why the third subject did not get regular EP. The remaining 18 subjects did not use preventative doses of antibiotics during the study nor did they develop any serious infections.

RESULTS BETA2-MICROGLOBULIN AND NEOPTERIN

In people with HIV, blood levels of Beta2-m and neopterin rise as the immune system weakens. In this study levels of Beta2-m remained stable in 16 subjects and decreased in 2 and increased in two others. Neopterin levels remained stable in 10 subjects, decreased in 3 and increased in 7.

RESULTS--CD4+ AND CD8+ CELLS

In one analysis in 13 subjects the production of T cells increased. CD4+ cell counts remained stable in 8 subjects. CD8+ cell counts increased in at least 12 subjects. When these tests were done in another laboratory, all results were the same except for CD8+ cell counts. According to the second laboratory, 14 subjects had either stable or increasing CD8+ cells.

RESULTS--TESTING T CELLS

When T cells from subjects were exposed to microorganisms (in simulated tests) about 40% of subjects had T cells that had an improved response compared to similar tests done before they entered the study. Fifty percent of subjects had a stable T cell response while in the study. The two subjects who developed PCP had T cells that failed their performance tests both before and/or during the study.

ANTIBODIES

Subjects continued to make anti-HIV antibodies at either high or low levels. These antibodies attacked HIV proteins including gp120, gp41 and p24.

HIV

p24 antigen (commonly called p24) is a fragment of HIV. During viral production p24 is usually produced by infected cells. Measuring p24 is cheaper and less accurate than 'growing' viruses to measure HIV production. During the study 16 subjects continued to "test negative" for p24. This suggests that viral production remained at low levels. In 4 subjects who had detectable p24 before the study, p24 levels fell in 3 and increased in the remaining subject.

WHY ARE SKIN TESTS DONE?

Researchers in this and other studies have injected small amounts of proteins from various microorganisms such as yeast and the bacteria that cause TB among others. In non-HIV-infected healthy patients with an intact immune system redness and swelling develop 24 to 72 hours after the injection. This type of testing is called DTH; delayed type hypersensitivity. In people with HIV infection the reaction to these proteins decreases as their immune systems weaken. Thus very ill patients may have a weak or even no reaction to these proteins. The reaction is an indicator of a type of immunity called CMI (cell-mediated immunity). CMI is needed to fight many of the infections that can kill patients with HIV/AIDS. DTH is a crude but useful way to find out the state of the immune system.

RESULTS--SKIN TESTS

At the beginning of the trial only 1 subject had a normal skin test response. During the study 9 subjects developed a normal skin test response and 4 other subjects developed a partial response. One subject who had no response to skin tests both before and during the study developed PCP. Another who lost his skin test response also developed PCP. These subjects are the same ones mentioned earlier in the section on life-threatening infections.

PHYSICAL EXAM AND QUALITY OF LIFE

Seventeen subjects either improved or remained stable during the study. Six subjects had increased weight, 13 had no change and 1 subject lost weight. In 9 subjects the size of their lymph nodes decreased, the opposite happened in 4 subjects. According to the results from a quality of life questionnaire, there was an increase in "well-being and fitness" in 18 subjects.

TOXICITY

There was a small, but not significant increase in blood levels of liver enzymes. There was no obvious toxicity caused by EP.

SUMMARY

Extracorporeal photopheresis (EP), a therapy for a fond of T cell cancer, has recently been used in subjects with ARC (AIDS-related complex). This therapy appeared to stabilize CD4+ cell counts in some subjects and also increase the CD8+ coll counts. In crude tests of immune functions, EP seemed to improve lie ability of T cells to fight invading microorganisms (in simulated tests) and boosted one arm of the immune system called CMI (cell-mediated immunity) m 13 subjects. Blood levels of Beta2-m, which rise as the immune system weakens, remained stable in 16 subjects. Doctors did not give subjects antibiotics or other drugs to prevent the life-threatening infections commonly seen in AIDS. In two subjects, PCP developed. These two subjects either lost their reactions to skin tests before the study or never regained them while in the trial. As EP did not increase production of HIV and appeared to stabilize or improve the health and well-being of subjects and boost CMI, the researchers involved suggested that a larger, controlled study of EP needs to be done. These researchers are planning such a study.

HOW DOES EP WORK?

Researchers are not sure how photopheresis might help the immune systems of people with HIV infection. The process may help to improve the ability of the immune system to find and attack HIV and infected cells. As well, EP helps some patients improve the performance of their T cells and increases the amount of CD8+ cells which are important in controlling infections. EP clearly has limits. Patients who have had life-threatening infections may not improve when given this therapy. EP has not returned the immune system to its normal state in any of the subjects used in the study. This is not surprising given that it can take 10 to 15 years for HIV-infected subjects to develop AIDS and it may take just as long to repair their immune systems. Long-term, controlled studies of EP may answer some of te questions about its effectiveness in the treatment of HIV infection.

REFERENCES:

1. Bisaccia E, Berger C, and Klainer AS. Extracorporeal photopheresis in the treatment of AIDS-related complex: a pilot study. Annals of Internal Medicine 1990;1 13(4):270-275.

2. Bisaccia E, Berger C, DiSpaltro FX and Klainer AS. Extracorporeal photopheresis in the treatment of ARC: extended trial. Journal of Acquired Immunodeficiency Syndromes 1993;6:386392..

3. Cohen J. T cell shift key to AIDS therapy? Science 1993;262(8): 175-176

4. Saed GM and Fivenson DP. Augmentation of Th1 cytokines in the peripheral blood of SZ patients upon treatment with extracorporeal photopheresis. Clinical Research 1993;41(3):664A.

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