|CD4+ counts||Inconsistent surrogate marker||Counting reliability||General|
|Disputing a Theory About AIDS Progression : Evidence suggests that a decrease in CD4 + T cells is not a death sentence|| ||Kling Jim
| ||For this article, Jim Kling interviewed Louis J. Picker, associate director of the Vaccine and Gene Therapy Institute at the Oregon Health Sciences University : "The proliferation studies [used to measure the presence of CD4+ T cells] have a six-day readout time," he says. "It's been shown that you're measuring the overall ability of T cells to proliferate under those conditions." In other words, cells that don't thrive in vitro might die in culture. At the experiment's end, those cells would be under-represented, leading researchers to conclude mistakenly that little or no CD4+ T cells were present in the sample. Our data suggests ... that HIV-specific CD4+ T cell levels are not an accurate marker of disease progression,.|
| ||The Scientist 15:17, May 14, 2001||2001|
|A systematic study of host defense processes in badly injured patients.|| ||Polk HC, George CD, Cost K, et al.
| ||Argue that the reduction in CD4+ lymphocytes probably does not represent cell death, but rather redistribution out of the bloodstream and into the tissues.|
| ||Ann Surg, 1986, 204; 282-301||1986|
|Reappraisal of the depletion of circulating CD4+ lymphocytes in HIV-carriers in transition to AIDS|| ||Hässig Alfred, Wen-Xi Liang and Stampfli Kurt
| ||With regard to where the CD4-cells migrate under the influence of cortisol, it has been shown in animal experiments that they are sequestered mainly into the bone marrow... The sequestration of CD4-cells to bone marrow may be considered as a general phenomenon in any severe and persistent hypercortisolism (an excess of cortisol in the blood) in acute-phase inflammatory reactions in which the whole body responds to an inflammation or injury (Fauci A.S. & Dale D.C, The effect of in vivo hydrocortisone on sub-populations of human lymphocytes, J. Clin. Invest., 53:240-246, 1974, Cohen J.J, Thymus-derived lymphocytes sequestered in the bone marrow of hydrocortisone-treated mice, J. Immunol., 107:841-844, 1972, M.A. Levine & H.N. Claman, Bone marrow and spleen: dissociation of immunologic properties by cortisone, Science, 167:1515, 1970)|
| ||Continuum vol.3 no.5, Jan./Feb. 1996||1996|
|Sources of variability in repeated T-helper lymphocyte counts from human immunodeficiency virus type 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important.|| ||Malone JL, Simms TE, Gray GC, Wagner KF, Burge JR, Burke DS.
| ||The authors compared the diurnal variation in HIV-positive and HIV-negative people, finding a significant variance in both. They found that both groups followed a pattern that coincides with known daily fluctuations of cortisol, with minimum CD4 levels occuring between 8:00 and 10:00 a.m., and maximums occuring at around 10:00 p.m. A flattening of the normal diurnal variation of cortisol, together with elevated average cortisol levels, is often seen in people under chronic psychological stress, and is also common in people diagnosed HIV positive. Malone et al.'s study of CD4 variation found that HIV-negative people had an average variation of 506 cells/mm3 each day, while HIV-positive people had only about 60 cells/mm3 of variation. The authors conclude that blood draws for CD4 counts should always be done at the same time of day, but they do not comment on relations between the diurnal cycle they observed and the diurnal variation in cortisol.|
| ||J Acquir Immune Defic Syndr 1990;3(2):144-51||1990|