An alien from another planet, or a naïve believer in the objective nature of science, might imagine that the central, single most important issue of HIV/AIDS theory is the mechanism by which HIV does what it is supposed to do, namely, destroy the CD4 T-cells whose subsequent absence leaves the unfortunate host helpless against opportunistic infections like Pneumocystis carinii pneumonia or candidiasis.
“We probably know more about how HIV produces its pathology than about the pathological mechanism of virtually any other microbe”, Robert Gallo asserted already in 1991 (p. 296 in Virus Hunting: AIDS, Cancer, and the Human Retrovirus: A Story of Scientific Discovery).
That alien and that naïve observer would naturally conclude that by 1991 it was fully understood, how HIV kills T-cells. As a stark matter of fact, though, two decades after Gallo’s assertion, it remains an unsolved enigma, how HIV could possibly do what HIV/AIDS theory demands of it.
Duesberg  first posed the conundrum of how HIV could damage the immune system when it is present in only 0.1-1 % of the lymphocytes it supposedly kills, and is expressed in only 1% of those in which it is present. There have been many imaginative speculations about how the tiny minority of infected cells could somehow cause the whole immune system to collapse , but those have been countered by Duesberg , and in any case none of the suggested mechanisms has been established by actual evidence. A continually updated website  mentions a number of possibilities, again none of which has been definitively established.
The current consensus, such as it is, seems to be that cells are killed by an unspecified “bystander” mechanism under conditions of “chronic inflammation” or “chronic activation”. In absence of any specific description of actual processes, those phrases deserve to be described and dismissed as “hand-waving”, the scientific euphemism for bullshit , utterances made without regard for their possible truth value. Insofar as chronic activation or inflammation might be interpreted as a high rate of turnover of immune-system cells, it should be recalled that this notion — the basis for introducing combination antiretroviral therapy, Highly Active Anti-Retroviral Treatment, in the mid-1990s — was shown to be faulty .
In any case, as of December 2013, after three decades of belief that HIV kills the immune system, there is no agreement over how it could possibly do so. Thus “Despite more than three decades of study, the precise mechanism(s) underlying the demise of CD4 T cells during HIV infection remains poorly understood and has been highlighted as one of the key questions in HIV research” .
Note that the common scientific euphemism “poorly understood” stands for “completely unknown”.
Such a stunning admission of the failure of HIV/AIDS theory is, of course, made only in the context of putting forward a new proposed mechanism, in this case “pyroptosis triggered by abortive viral infection”, which also raises “the possibility of a new class of ‘anti-AIDS’ therapeutics targeting the host rather than the virus” .
This latest breakthrough was significant enough to be broadcast to the media even before the actual publications had appeared.  was even marked “NOT FINAL PROOF”. Observers of the cutthroat competitiveness in research will also note the skill with which much the same work has been published simultaneously in Nature and in Science, and how the media fell right in by parroting the extravagant claim: “How HIV destroys immune cells”  — forgetting, apparently, that half a year earlier an entirely different mechanism and potential treatment had been ballyhooed: “Scientists discover how HIV kills immune cells; findings have implications for HIV treatment” .
Fauci pronounced the pyroptosis stuff “really elegant science . . . . It goes a long way to explaining what has been an enigma for practically 30 years” — acknowledging once again that the mainstream hasn’t had a clue for 30 years about the central issue in HIV/AIDS theory; and “going a long way” remains far from actually reaching a goal.
Not that this new understanding, with its implication of an entirely new approach to treatment, would actually supersede anything: “Fauci said such an approach would not replace antiretrovirals (ARVs), which suppress HIV replication and halt disease progression. But it could be used in combination in people who are dealing with highly resistant HIV strains . . . . One of the things about blocking the host response is that it’s very difficult for the virus to mutate to counteract it” [9a].
The lead investigator on the pyroptosis work was suitably modest even as he raised highly unlikely possibilities: “If we get rid of chronic inflammation, will we stop the homeostatic proliferation and degrade the latent reservoir? . . . If it does, caspase-1 inhibitors might — and I emphasize might — become a component of a curative cocktail”.
No matter, really. Ample grounds here for lots more research and the associated research funds.
I venture a prediction: None of these hopes and possibilities will pan out, and nothing more will be heard about them in the future.
 Peter H. Duesberg, “Retroviruses as carcinogens and pathogens: Expectations and reality”, Cancer Research, 47 (1987)1199-1220
Anthony A. Fauci, “The Human Immunodeficiency Virus: Infectivity and mechanisms of pathogenesis”, Science, 239 (1988) 617-22; Alfred S. Evans, “Does HIV cause AIDS? An historical perspective”, Journal of Acquired Immune Deficiency Syndromes, 2 (1989) 107-13
 Duesberg, “Does HIV cause AIDS?”, Journal of Acquired Immune Deficiency Syndromes, 2 (1989) 514-7
 Harry G. Frankfurt, On Bullshit, Princeton University Press, 2005
 Craddock, “HIV: Science by press conference”, pp. 127-30 in AIDS: Virus or Drug-Induced?, Kluwer, 1996; Duesberg & Bialy, “Duesberg and the right of reply according to Maddox-Nature”, pp. 241-70 in AIDS: Virus or Drug-Induced?, Kluwer, 1996; Roederer, “Getting to the HAART of T cell dynamics”, Nature Medicine, 4 (1998) 145-6; Yates et al., “Understanding the slow depletion of memory CD4+ T cells in HIV infection”, PLoS Medicine, 4 (2007) e177
 Monroe et al., “IFI16 DNA sensor is required for death of lymphoid CD4 T cells abortively infected with HIV”, Sciencexpress, http://www.sciencemag.org/content/early/recent / 19 December 2013 / Page 1/ 10.1126/science.1243640
 Doitsh et al., “Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection”, Nature, 2013, doi:10.1038/nature12940
 19 December 2013: [a] Dan Cossins, The Scientist; http://www.the-scientist.com/?articles.view/articleNo/38739/title/How-HIV-Destroys-Immune-Cells;
[b] Anna Azvolinsky, “HIV’s killer tactics revealed, new therapy approach found”, http://www.livescience.com/42101-how-hiv-kills-white-blood-cells-self-destruction.html;
 5 June 2013, http://www.sciencedaily.com/releases/2013/06/130605144435.htm