translation agency

(CATIE) IMMUNOMODULATORS: A small study finds no benefit from thymic hormone
Sean Hosein
May 1, 1996
TreatmentUpdate 68, Volume 8, No 4; May-June 1996

Background In 1995, researchers in the USA reported that short courses of interleukin-2 (IL-2) dramatically increased CD4+ cell counts in 6 subjects with HIV-infection. Recently, another research team has been conducting experiments with IL-2, giving it to a small group of subjects together with another immune booster thymosin alpha1. Produced by the thymus gland in the chest, thymosin alpha1 has increased CD4+ cell counts when used in one study with AZT (see TreatmentUpdate 52).

Study details The research team in California used 12 HIV-infected and symptom-free subjects (1 female, 11 male). Before they received thymosin alpha1, the average CD4+ cell count was 135 cells. Subjects used AZT 600 mg/day for at least 2 months before entering this study. The researchers gave subjects a long-acting form of IL-2 called PEG-IL-2 (polyethylene glycol IL-2) in a dose of 1 million units/square metre of skin for half an hour, "every other week for 20 weeks." Eight weeks into the study researchers gave the subjects thymosin alpha1 0.4 �g/m2 twice weekly injected under the skin. At the 12th week researchers "increased the dose of [thymosin-alpha1] to 1600 �g/M2 for an additional 8 weeks." Results---CD4+ cells, HIV production After each infusion of PEG-IL-2 CD4+ cell counts rose from pre-study levels of 135 cells to 193 cells. The next week, CD4+ cell counts fell to their pre-study level. Each time subjects received PEG-IL-2 the same pattern in CD4+ cell changes occurred. The temporary increase in CD4+ cell counts was statistically significant only for the first 10 weeks of the study. After this point, the increased CD4+ cell counts following the infusion of PEG-IL-2 were no longer statistically significant. The performance of CD4+ cells in responding to simulated attack by bacteria, fungi and viruses did not change during the study. The amount of HIV produced in the subjects during the study did not significantly change.

Toxicity When given PEG-IL-2 subjects experienced "fatigue, headache, nausea, vomiting, fever...muscle pain [for the next 24 hours]." Giving the subjects the anti-inflammatory drug ibuprofen (Motrin ) before the infusions "reduced the severity of symptoms." The combination of drugs used in the study did not cause life-threatening complications.

Overall Use of the immune booster PEG-IL-2 temporarily increased CD4+ cell counts. After the 10th week the increased numbers were no longer statistically significant. Use of thymosin alpha1 did not cause any "significant change in CD4+ cell number[s]." The California team suggested that testing the combination in subjects who have more than 200 CD4+ cells may provide better results.

REFERENCES: 1. Ramachandran R, Katzenstein DA, Winters MA, et al. Polyethylene glycol-modified interleukin-2 and thymosin alpha1 in Human Immunodeficiency Virus type 1 infection. Journal of Infectious Diseases 1996;173:1005-1008.