HIV-negative AIDS?

We couldn’t find a single doctor willing to go on the record about HIV-negative AIDS. — Katie Peoples, HIVPlusMag

If anyone mentions the term “HIV negative AIDS” in polite society, the reaction tends to be at best confusion and at worst derision. Technically, this reaction is entirely reasonable, given that AIDS is defined exclusively in the presence of antibody to HIV. By its very definition, HIV-negative AIDS is an impossibility. It remains the case that, for example:

Cervical cancer + antibody to HIV = AIDS

Cervical cancer without antibody to HIV = Cervical cancer

This example could easily be repeated with any of the main AIDS-defining illnesses as reported by official sources such as the CDC or the WHO. A cursory glance at the list of such illnesses reveals some curiosities indeed. Indeed, one such illness is “herpes simplex: Chronic ulcer(s) (more than 1 month in duration.” This same document lists neoplasms such as Burkitt’s lymphoma and immunoblastic lymphoma, as well as the aforementioned invasive cervical cancer. It also lists salmonella septicemia, candidiasis of the lower respiratory system, and “recurrent pneumonia.”

It has been pointed out many times that every single one of these disease states exists in the absence of HIV. Further to that, in the early days of AIDS, the only reason that any new pathology was considered to be present was that patients were presenting with one of a small handful of diseases that were previously rare among healthy individuals. These diseases were Kaposi Sarcoma, cytomegalovirus infection of the eyes/brain, and pneumocystis pneumonia. Today, Kaposi Sarcoma, which was arguably the most dramatic AIDS-defining illness in the early days (remember that Tom Hanks movie, Philadelphia?), and presented by way of alarming purple skin lesions (which often also affected the lungs), is no longer considered to be attributed to HIV at all, but to a herpes virus, human herpesvirus 8 (HHV-8). According to various studies, Kaposi Sarcoma has all but disappeared as an AIDS-defining illness, and of the original cohort of such illnesses, only pneumocystis pneumonia, which is clinically indistinguishable from regular pneumonia, and esophageal candidiasis, remain frequently diagnosed.

Their incidence has now been eclipsed by tuberculosis, driven perhaps in large part by the African AIDS epidemic. Tuberculosis, globally, is as common as mud, and its inclusion as a disease defining a rare immunological deficiency disease is at best problematic.

More troubling even than this is that according to independent studies, the most common causes of death — note here that we are referring to mortality and not morbidity or illness — among HIV-positive individuals are either neoplasms (cancers) or, in the case of the Zhejiang study, suicide, accidents, and substance abuse, a trend noticed also in a cohort study in Spain. In this study, the most common causes of death were liver failure, a known adverse effect of AIDS drugs, drug overdose, suicide, cancer, and cardiovascular disease. Note that none of the AIDS-defining opportunistic infections of the 1980s and early 1990s even make the list. Note also that none of these diseases, with the possible exception of some cancers, are even related to immune deficiency at all.

Digging a little further, we note the addition in 1993 of a low T-cell count in the absence of clinical illness to the CDC list of AIDS-defining conditions. Specifically, a patient can be diagnosed with AIDS based on a positive HIV antibody test accompanied by a one time CD4+ T cell count of fewer than 200/mL. (For reference, the “average” CD4+ T cell count in healthy people is assumed to be 1000/mL, although the variance is large and typically, HIV-negative individuals never have their CD4+ T cells quantified in this way. It is a laboratory test by and large limited in its scope to HIV positive individuals.) Note also that this result is based on the lowest CD4+ T cell count measured, so that even if the patient’s CD4+ T cell count rebounds, they are now an AIDS patient.

How many HIV-antibody-negative people would find their CD4+ T cells to be alarmingly low if they were ever measured? This is a tantalizing question, whose answer we may never fully arrive upon, but it is instructive to note that in 1992-93, the same year that the CDC revised and expanded their list of AIDS-defining illnesses to include the low CD4+ T cell definition of AIDS, a new immune dysfunction disease was noted among HIV-negative individuals. The fancy name for it is idiopathic CD4+ lymphocytopenia, a mouthful of a name that means “unexplained persistently low CD4+ cell counts” in the absence of antibody to HIV. It is defined as “a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections.” In other words, it is precisely HIV-negative AIDS. ICL is considered “rare,” although one wonders how often it would be found were we looking for it, rather than assuming that AIDS — or more broadly, immune dysfunction — only occurs in the presence of antibody to HIV.

Zooming out further, we note that the key defining laboratory anomaly in AIDS, the depletion of CD4+ T cells (whose mechanism of occurrence is still not understood), is no longer the sole focus of consideration. Indeed, “HIV-mediated inflammation,” leading to the appearance of cancers and cardiovascular events that increasingly define AIDS mortality and which have little to do with immune deficiency, is increasingly the subject of research efforts. AIDS is certainly far from being the only disease state characterized by “massive inflammation”; indeed, inflammation is very common in autoimmune disease states, which is more similar to immune over-activation rather than immune depletion, long considered to be the hallmark of AIDS.

What if it is actually the case that “AIDS” — acquired immune deficiency syndrome — is in fact a much broader condition than the “HIV is the necessary and sufficient cause of AIDS” model would indicate? Certainly the diseases that are now common among HIV-positive patients and AIDS patients indicate that this is likely, considering how common they are even in HIV-negative individuals. Consider also that morbidity states related to autoimmunity and inflammation are on the rise in the general population. What would it mean for people suffering these disease states — including but not limited to rheumatoid arthritis, lupus, Lyme Disease, ME/CFS, fibromylagia, and many more — if we were to zoom out and consider that these diseases share a similar causation, which by definition cannot be HIV? What would this mean for research and treatment?

“AIDS research” has thus far been almost a complete failure. I have listed its failures frequently and often, so I will not list them again except to note that the only treatments we have for HIV appear to hasten death due to liver failure and cardiovascular events, and that we still do not understand what mechanism of action is responsible for the immune deficiency as defined by CD4+ T cell depletion.

I posit that the fatal mistake we make is in assuming that immune dysfunction and AIDS are caused solely by HIV — with disastrous consequences for patients who are “retained in care” (slaves to the toxic anti-HIV drug regime) or worse, commit suicide because of their diagnosis. This spectacular mistake endangers not only the lives of those diagnosed HIV-positive but also the lives of the many people suffering HIV-negative immune dysfunction worldwide. The scientific community is failing both groups by stubbornly remaining laser-focused on the “HIV only” model of AIDS. We need to do better. In next week’s post, I will dive deeper into the laboratory anomalies of HIV patients and of patients with non-HIV immune deficiencies and dysfunctions, to demonstrate what patterns emerge.