Item #39: Does HIV Cause Disease by Killing CD4 Immune Cells?

[Duesberg] simply pointed out that no one had yet proven that HIV is capable of causing a single disease, much less the twenty-five diseases that are now part of the clinical definition of AIDS. He pointed to a number of paradoxes regarding HIV and argued that far from being evidence that HIV is “mysterious” or “enigmatic,” these paradoxes were evidence that HIV is a passenger virus.

Farber appears to agree with Duesberg's view that HIV is incapable of causing a single disease.

HIV causes a progressive decline of the immune system by depleting CD4+ T-cells. Eventually the immune system becomes dysfunctional and incapable of fighting off diseases that it normally would. People with advanced HIV-disease are more susceptible than the general HIV-negative population to about 30 different diseases, many of them with high mortality rates.64

The Gallo document is parroting an old and discredited theory, that HIV directly kills CD4 immune cells, the ‘hallmark’ of AIDS. Listen to some recent commentators address the mystery of the low level of infection of CD4 cells and lack of evidence for cell-killing capabilities:

• “HIV-1 infects CD4+ T cells but direct infection and killing of these cells can only partly account for HIV-1-associated lymphocyte depletion. The actual number of productively infected cells is estimated to be relatively low, in the order of 5 X 10^7 to 5 X 10^8 CD4+ T cells whereas the human body contains an average of 2.5 X 10^11 CD4+ T cells. Direct infection of CD4+ T cells does not explain the loss of naive CD8+ T cells that parallels the decline in naive CD4+ T cells during asymptomatic HIV-1 infection.” [1]
• “According to one paradigm, the demand for CD4 T cell production in response to rapid virus-mediated destruction is the direct cause of increased turnover. Progressive depletion of CD4 T cells is accordingly seen as a failure of production to keep up with the rate of loss. This hypothesis has been challenged on several grounds” [2]
• “Clearly the change in CD4/CD8 ratio [often declared to be the hallmark of AIDS] and immune function is multifactorial and cannot be explained solely by a model of CD4+ cell destruction by virus” [3]
• “Two years before the virus that causes AIDS was discovered, physicians in the United States and Europe realized that the defining symptom of the mysterious new disease was the loss of a specific immune system cell population, called CD4 cells. Twenty years later scientists still don't know what kills the cells. And its eventual discovery will be key to understanding AIDS - defined as a rise in the numbers of viruses in the bloodstream coupled with a fall in the CD4 cell count. [However]...it is not in HIV's interests to kill off its "home" [CD4] cell, most scientists believe a complex interaction is at play, causing the cells’ deaths” [4]
• “Controversy continues regarding the effects of HAART on CD4 T-cell production...our understanding the mechanisms that lead to depletion of CD4 T cells remains incomplete. The observation that T-cell turnover in SIV-infected mangabeys appears to be normal, despite high viral loads, has reinforced the hypothesis that indirect mechanisms may be largely responsible for increases in T-cell turnover, yet there is little solid evidence on how HIV and SIV mediate this effect” [5]
• “The lack of congruence between clinical classification and immunological depletion emphasizes the importance of considering parameters separately...In areas without access to CD4 counts, some children with severe immunological depletion might be missed. Alternatively, a high CD4 count or percentage does not preclude severe disease.” [6]
• “Immunological status [largely CD4 cell counts] generally poorly reflected clinical condition” [7]
• “At present there is no convincing evidence that the current surrogate markers [including CD4, CD8 and viral load measurements] can be reliably used to predict the clinical efficacy of new treatments.” [8]

1. Hazenberg MD et al. T cell depletion in HIV-1 infection: how CD4+ cells go out of stock. Nature Immunology. 2000 Oct; 1: 285-9.
2. Sousa AE et al. CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load. J Immunol. 2002 Sep 15; 169: 3400-6.
3. Rosenberg YJ et al. HIV-induced decline in blood CD4/CD8 ratios: viral killing or altered lymphocyte trafficking? Immunology Today. 1998 Jan; 19(1): 10-17.
4. Garrett L. Immune cell deaths still a stubborn puzzle. Newsday. 2001 Jun 5; C08.
5. Johnson RP. The dynamics of T-Lymphyocte turnover in AIDS. AIDS. 2000; 14(suppl 3): S3-9.
6. van Kooten Niekerk NK et al. The First 5 Years of the Family Clinic for HIV at Tygerberg Hospital: Family Demographics, Survival of Children and Early Impact of Antiretroviral Therapy. J Trop Pediatr. 2005 Jun 9.
7. The European Collaborative Study. Fluctuations in Symptoms in Human Immunodeficiency Virus-Infected Children: The First 10 Years of Life. Pediatrics. 2001 Jul; 108(1): 116-22.
8. Peto T. Surrogate markers in HIV disease. Journal of Antimicrobial Chemotherapy. 1996 May; 37 (Suppl. B): 161-170.