Wednesday, December 7, 2011

Debunking the Doublet: Study Finds Lack of Suggested Relationship Between IL-7 and CD4 T Cell Populations in Longitudinal Assessment of HIV Patients

Seventy-two patients with HIV participated in a recent study done by the European Union to investigate the correlation between IL-7 and CD4 T cell population density. The results of the study will be published in the December 15, 2011 edition of the Journal of Acquired Immune Deficiency Syndromes (vol 58, issue 5, pages 436-441), but is published in advance online. Thirty of the patients did not use anti-retroviral drugs and forty-two did, making up the two populations used in the study. T cell and IL-7 counts were taken regularly for 46 +/- 14 months in the two populations. The researchers then used multi-variable linear regression analysis to analyze the statistical significance of the potential IL-7/CD4 T cell correlation.
HIV is an acronym for Human Immunodeficiency Virus, a retrovirus that infects humans and is transferred through the direct sharing of bodily fluids through sexual intercourse, blood transfusions, or the sharing of syringes. There is no known cure or vaccine for HIV, and there are several challenges that make such a necessary product difficult to formulate. Primarily, HIV is a quickly mutating virus, which ensures that the virus readily mutates to avoid any single drug that is aimed against it. Another difficulty encountered when attempting to make and test a potential drug is that there currently exists no appealing animal model in which to test HIV treatments and vaccines. Chimpanzees respond to SIV, a virus similar to HIV but that infects chimps, but they never progress to AIDS. Also, chimpanzees are an endangered species, which makes using them as an animal model ethically questionable and difficult to obtain approval for.
Cytheris, a biopharmaceutical company that works with immune enhancement, has had success in mouse trials using IL-7 to treat HIV, and is currently working on Phase I clinical trials with a new HIV drug based on these results.1 This has led to much investigation of the link between IL-7 and HIV, one outcome of which is this study. CD4 T cells are often the first immune system element that comes to mind when pondering HIV, as these are the main targets of the virus. HIV infects and brings about the death of CD4 “helper” T cells, and when the CD4 T cell count falls below 200 cells per cubic mm of blood the patient is considered to have progressed from HIV to AIDS. Thus, CD4 T cells were suggested as the link between HIV treatment and IL-7. However, the perhaps most likely link between IL-7 and the treatment of HIV, CD4 T cells, did not produce the expected results.

The study found that in untreated patients, CD4 T cell levels decreased to a statistically significant point (P<0.0001), however IL-7 levels and HIV mRNA levels did not significantly change. Thus, there was no correlation between IL-7 levels and CD4 T cell count. For the population on highly active retro-antiviral drugs, the CD4 population significantly increased (P<0.0001) and the IL-7 count decreased (P=0.1). Thus, this population did not show a directly proportional relationship as has been previously suggested. This derails the suspected correlation between IL-7 and CD4 T cells.
Rallon, N. I., M. Lopez, S. Lozano, J. M. Sempere-Ortells, V. Soriano, and J. M. Benito. "Longitudinal Assessment of Interleukin 7 Plasma Levels in HIV-Infected Patients in the Absence of and Under Antiretroviral Therapy." Journal of Immune Deficiency Sydromes 58.5 (2011): 436-41. Print.
Other Sources:
1) "Cytheris - IL-7 HIV Trials." Cytheris - The Immune Enhancing Company. Cytheris, 2010. Web. 07 Dec. 2011. .

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