A Paradigm Shift on AIDS Is Overdue

 Everyone knows what HIV and AIDS are. HIV-1 is the human immunodeficiency virus that gradually causes the immune system to decline to the point we call AIDS - acquired immune deficiency syndrome. That occurs when CD4 white blood cells fall to dangerously low levels causing the immune system to no longer function properly. Then various opportunistic infections – OIs - can gradually take over the body. These symptoms and OIs include excessive inflammation, fungal infections, cancers, hepatitis, and the mycobacterial infections tuberculosis and pneumonia. They also include muscle wasting and can terminate with cardiovascular events like heart attack and stroke.

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            What is a paradigm?

            A paradigm is a pattern – a way of systematically arranging concepts to understand them better. Mathematics is composed of paradigms such as the multiplication table. Language grammar is a paradigm indicating proper sentence structure. Scientists use paradigms to systematize, understand and explain complex aspects of nature. Scientific paradigms can change as new patterns are discerned after additional facts that cannot be accounted for by the ruling paradigm come to light. When that happens, a paradigm shift occurs.   

            Centuries ago, everyone thought the world was flat. If a ship sailed too far from land it would fall off the edge of the Earth. Gradually there was a paradigm shift in understanding that recognized that Earth is actually round like a globe. That explains the phenomena that when a ship sails back into view, people see the top of the sails first, and only after that the whole ship appears.

            Aristotle thought Earth was the center of the universe and everything, the sun and stars, all rotated around it. That appeared to be correct, but it turned out not to be. As scientific observations improved, we learned the sun is the center of our solar system and Earth and the other planets revolve around it. Eventually we realized our sun is only one among millions of stars in the universe. This paradigm shift allowed us to understand what a small place Earth occupies in the cosmos, and how lucky we are to live on this special planet whose environment we must protect.  

            When scientists make discoveries, they develop paradigms to explain those novel observations. Sometimes those are 100% correct the first time. However often a paradigm must be adjusted as additional phenomena are noticed. An accurate scientific paradigm must explain all the observed relevant facts, not just some of them. If a paradigm cannot account for all the relevant phenomena, the paradigm is inadequate, or simply wrong. Then it must be modified, discarded, or replaced.

            Today almost all people working in the field of AIDS explain the way HIV causes AIDS is that HIV infects CD4 white blood cells. HIV viruses multiply within in a cell until there are so many the cell bursts, dying and releasing the viruses. This action repeats until the CD4 cell count declines to the point a person has AIDS – defined as having less than 200 CD4 cells per milliliter of blood. When the virus has killed enough CD4 cells and the CD4 count falls low enough that OIs become overwhelming, a person dies. This is what AIDS educators are taught and what they teach others. But this accepted paradigm is grossly insufficient – and wrong. This original, premature, flat-earth explanation of how HIV causes AIDS does not explain all the phenomena. Certain critical facts that are absolutely central to this process are completely ignored because they were not recognized when the original paradigm was constructed shortly after HIV was discovered and accepted as the sole cause of the disease. Therefore, these essential factors were left out of the equation. That would never work in mathematics.  

            In 2001, Dr David Ho pointed out the problem with this overly simplistic paradigm in his keynote address to the First Scientific Conference on AIDS in Buenos Aires, Argentina. Dr. Ho is one of the most imminent AIDS researchers in history. This American scientist is largely credited with developing the protease inhibitor class of drugs that in 1996 finally stopped the wholesale dying of the early AIDS epidemic. He deserves a Noble Prize.

            In his opening lecture to three thousand AIDS researchers gathered in Buenos Aires for the first “scientific” conference on HIV/AIDS, Dr. Ho explained that the original paradigm of how HIV causes AIDS could not possibly be correct. Ho emphatically announced to the scientific gathering that it was “scientifically impossible” for HIV to cause AIDS the way we believe it does, because HIV infects less than one percent of CD4 cells. HIV cannot kill all the millions of CD4 cells in the body if it never infects more than one percent of them. He said, “Something else must be happening.” As I listened to David Ho, I was struck by his argument because no one had ever questioned the original, still current version of the AIDS causation paradigm. He made sense. “Something else must be happening.” But what is that something else? After carefully analyzing all the significant phenomena, the existing AIDS paradigm fails to account for one central aspect of HIV progression. That is the progressive loss of selenium. Recalculating that into the equation allows scientists to arrive at a corrected, global AIDS causation paradigm. 

            By 2000 more than twenty scientific papers reported that as CD4 counts decline, selenium levels in the body decline in tandem. (1) Thus, one must ask, is the decline in CD4 causing selenium to decline? Or is the decline in selenium causing CD4 count to decline? Which is the cause, and which is the effect?  Which is the primary driver of this mutual decline in immune correlates? How can this be explained properly?  

By 2002 more than seventeen medical journal articles stated as an established fact that higher levels of selenium could slow progression of HIV becoming AIDS. How? That must be accounted for in any accurately constructed paradigm. Many journal articles have reported that selenium possesses antiviral activity and can inhibit HIV replication via multiple immunological mechanisms – but only to a limited extent. Is there something else?

In 1997 Dr Marianna Baum’s research group “showed that selenium-deficient patients are nearly 20 times more likely to die from HIV-related causes than those with adequate levels.”(1,2) In 1999, one of the world’s leading experts on selenium, Vadim Gladyshev, reported that “there is a direct correlation between a low dietary selenium intake and a 20-fold increase in risk of developing AIDS in HIV-infected individuals.”(3) Baum’s group then reported “that low plasma selenium is a significantly greater risk factor for mortality than low [CD4] count, by a factor of 16…”(1,4) This is important.  

            Working with a top scientist from Harvard University, in 2006 the Nigerian Institute for Medical Research published a report at the Toronto AIDS Conference showing that, in quite advanced AIDS patients with an average of only 50 CD4 cells, adding just one tablet of 200mcg selenium to a regimen of HAART – highly active anti-retroviral therapy including protease inhibitors - more than doubled the increase in CD4 cells compared to HAART therapy alone. (5) Adding selenium to HAART tripled the increase in hemoglobin – reducing anemia. And adding 200mcg selenium daily significantly reduced opportunistic infections and hospitalizations. (5) Dozens of medical journals have reported that selenium reduces the incidence of virtually all opportunistic infections related to AIDS. Thus, there are multiple inter-actions between selenium and HIV/AIDS, none of which can be explained by the original paradigm. Obviously, something else - something related to selenium is going on.  

            Finally, in 2015, the Rwandan Ministry of Health working with Canadian scientists issued a report in the journal AIDS showing that in patients who were not yet on antiretroviral drugs, just one tablet of 200mcg selenium daily slowed progression of HIV becoming AIDS by 43.6%. (6) The outmoded AIDS paradigm explains none of these “observations”, another word for phenomena.

            So precisely, what else is going on?

            Chemists sometimes explain that humans are like chemical soup. We are composed mostly of hydrogen and oxygen - H2O - water. Viruses are also constructed of basic chemical elements. Where do viruses acquire the elements they use to form the proteins they are made of? They commandeer them from the cells and organs they infect. Biologists sometimes refer to selenium as “the universally protective element”. Every cell in the body contains selenium. It constitutes the active part of glutathione peroxidase – GPx - the universal antioxidant that helps clean, protect, and detoxify every cell and organ. When cells lose their selenium, they also lose their antioxidant protection. They get sick and are eventually instructed to self-destruct through a process known as apoptosis or programmed cell death.    

            Viruses evolved to steal or “highjack” selenium from cells. Influenza and almost all other viruses do this. When a person catches flu, within three days the level of selenium in the alveoli cells lining the lungs falls by 40%. That makes alveoli cells sick, the lungs sick, and then the person sick. The same thing happens with Ebola. As Ebola expert Dr Ethan Will Taylor explained, Ebola does in ten days what it takes ten years for HIV to do. What is that?

Ebola drains selenium from the immune and antioxidant systems so fast that both systems collapse, and the person dies – on average in less than three weeks with Ebola. In the 2014-16 Ebola epidemic in West Africa, moderately high-dose selenium supplements - 1.2mg daily - proved to be the only specific treatment that significantly increased survival – by 54.5%

Most viruses are selenium thieves. Viruses infect different cells in the body – the cell types they possess the molecular keys to unlock and enter through cellular receptors. Once they infect a cell, they utilize the cell’s selenium supply for their own replication. Selenium is the key protective element needed to maintain both the antioxidant and the immune systems. Stealing and thus depleting cellular selenium is one way viruses subvert the body’s own immune defenses, allowing viruses to survive and replicate more easily. How does HIV use selenium? Why does it need it?

Just as a person’s skin and clothes protect their body, HIV possesses a protective outer protein envelope. The viral ENV gene encodes an envelope protein that include selenium – a selenoprotein – that composes part of HIV’s envelope. Thus, every time an HIV virus is produced, it uses up an infinitesimal amount of this element. As HIV replication increases and a person’s selenium level falls, the lower level of selenium in the body signals the thymus gland that produces both CD4 and CD8 cells to switch gears to make fewer CD4 cells, and more CD8 cells. This alters the CD4/CD8 ratio for the worse. Therefore, HIV does not cause AIDS by killing CD4 cells. It causes AIDS by draining the body’s reservoir of selenium. That signals the thymus to reduce production of new CD4 cells. However, if a person takes selenium tablets and raises the level of selenium in the body, the thymus switches back to making more CD4 cells and fewer CD8. That is how taking selenium supplements increases CD4 count and helps against HIV, cancer, opportunistic infections, and other diseases associated with immune deficiency.

            None of this can be explained by the current “flat-Earth” paradigm of HIV causing AIDS by killing CD4 cells. That misunderstanding of HIV pathogenesis should be tossed onto the junkpile of premature, flat-Earth scientific theories. Yet that broken paradigm is still taught, and universally believed, despite its logical impossibility. That is a false, misleading theory that impedes therapeutic progress. While it served its purpose early in the AIDS pandemic to help explain this complex disease, when people needed a simple explanation. Today it obstructs a proper analysis of HIV pathogenesis. To understand AIDS based on a paradigm that explains all, not just some of the scientific phenomena, one must admit the need to shift the paradigm and even change the name of this disease. It would be more correct to call it Acquired Immune Deficiency of Selenium – AIDS. That explains both how HIV causes AIDS, and what the essential feature of this disease is. That central feature is the viruses’ progressive depletion of selenium that causes CD4 count to decline not by killing CD4 cells, but by reducing production of new CD4 cells. It also explains why OIs occur and why selenium therapy can largely reverse those.      

Unfortunately, the idea of a paradigm shift on AIDS causality disturbs pharmaceutical companies, researchers, activists, and AIDS NGOs that have invested so much in that sacrosanct ideology. All these groups have strong attachments to the current, long prevailing paradigm. Thus, it is important to recognize this shift does not question the cause of the disease, nor how we treat it. The human immunodeficiency virus causes AIDS, but it causes CD4 count to decline via a completely different mechanism than previously thought. This paradigm shift also does not question the use of protease, reverse-transcriptase and integrase inhibitor drugs to suppress viral replication. Instead, it improves the range of HIV therapy by recommending a safe, effective complementary approach to treating it, as well as for treating virtually all other opportunistic and co-infections by raising CD4 counts above the threshold for those conditions. Selenium is the icing on the cake of antiretroviral therapy. It adds another dimension to the therapeutic approach and expands the pharmaceutical armamentarium not only for HIV but for most viral infections. Adding selenium is the fastest way to increase CD4 count.    

            Although scientists have proved selenium inhibits HIV replication naturally through multiple immunological mechanisms, it does not inhibit replication nearly as effectively as advanced antiretroviral ARV drugs that are specifically designed to suppress the virus. Instead of acting primarily as the natural antiretroviral agent that it is, selenium supplements exert their potent effect as an immune booster by increasing CD4 production by the thymus. Oddly, no one has ever adequately explained how ARVs increase CD4. How do they? In some cases, they do not – at least not by very much.   

            ARVs reduce viral replication. How does that increase CD4 count? The correct scientific explanation is that since ARVs suppress the production of the virus that depletes selenium from the body, once viral replication stops draining the body’s selenium pool, the remaining reservoir of selenium gradually refills through dietary replenishment. Then higher levels of selenium signal the thymus to increase CD4 production. (7)  

            Naïve CD cells originate in the bone marrow. They migrate to the thymus gland, the CD cell university where these cells are processed and detailed. Finally, CD4 cells are tested for autoreactivity before the few that pass that final exam are released into the lymphatic system and the bloodstream. That is why these cells are called “T” cells, or thymic cells. The thymus produces both CD4 helper cells and CD8 suppressor cells, as well as subsets of these. The thymus is like an auto plant that produces two different car models and details them slightly differently according to the impulse and demand of the immunological marketplace.

            The thymus has a proverbial assembly-line switch that determines how many CD4 models are produced versus how many CD8 models are. The level of selenium in the body provides the signal that directs the thymus to product more of one, or more of the other. If selenium levels are high, more CD4 are produced. If selenium is low, the thymus produces fewer CD4 and more CD8.(7) The human body contains several million CD4 cells that, except for a very few memory cells, have a life span of only four days. Thus the thymus must pump out at least a million new CD4 cells every day. The level of selenium determines both the relative production of CD4 and CD8 cells, and thus the CD4/CD8 ratio. The CD4/CD8 ratio is an even better measure of overall immune competence than CD4 count alone. This has implications for many aspects of treating HIV and its sequelae.     

            Another consideration for public health is the availability of selenium in the soil and diet. Some countries including the United States, Japan and Venezuela enjoy high selenium content in their soil and diets. Most countries do not. Over decades, intensive agriculture using fertilizers that leach selenium from the soil have depleted the selenium content of farming soils. Some soil types are naturally deficient in this essential trace element. In fact, Sweden and New Zealand have augmented selenium enriched fertilizers back into their soils to help reduce high cancer rates. Most commercial livestock feeds are supplemented with selenium to help keep herds and flocks healthy, improve fertility, boost growth, and reduce the spread of disease. Humans have no such luck. Unfortunately, the soils of Southern Africa from the Democratic Republic of the Congo southward are mostly deficient in selenium, with Namibia and Tanzania the two exceptions. Across Southern Africa approximately half the population is deficient. Deficiency is more common in some countries including Zambia, Malawi, Zimbabwe, Lesotho and the uplands of Kwa-Zulu Natal province in South Africa. This Southern African region forms the epicenter of the world’s AIDS pandemic. The inadequacy of dietary selenium not only contributes to the prevalence of HIV, but also to the overall disease burden. Unfortunately, when a person is sick with AIDS or another disease, it is impossible to obtain enough selenium quickly through the diet to make up that difference. However affordable selenium supplements can rapidly remedy that deficiency. 

            HIV specialists in Africa have noticed that although most patient’s immune systems gradually recover after starting HAART therapy, five to seven percent of patients do not regain sufficient immunity as expected. This reinforces the fact that ARVs by themselves do not increase CD4 count. It is likely this group of patients are relatively non-responsive because they are severely lacking in dietary selenium. This is probably the reason they do not recover adequately even though the virus is fully suppressed.

Although all foods contain a tiny amount, most foods are not abundant in this trace mineral, especially fruits and vegetables. People get most of the selenium in their diet from the staple grains they eat, wheat, rice or corn, and from meat and eggs. Organ meats like liver, and seafood are especially rich sources. However, a corn-based diet is lower in selenium than a wheat-based diet, and a vegetarian diet will be lower than a meat rich diet. Thus, a rural, subsistence diet will contain much less selenium than one based on an array of foods purchased in a supermarket. The level of selenium in the soil is reflected in the food grown there.    

            What does the shift in the AIDS causation theory imply for using selenium supplements as an adjunct, complementary therapy for HIV disease?

            Despite proposals, plans, projects, and projections set forth by UNAIDS, millions of people with HIV in some African counties still receive inadequate, or no treatment at all for their disease. Some are not judged “ready” for therapy. In luckier countries “test and [immediately] treat” programs cover 100% of the HIV positive population. Given the affordable cost of selenium therapy and the fact just one tablet can slow HIV progression by 43.6%, and that selenium can help against many other diseases and conditions, including co-infections like hepatitis and tuberculosis, there is no excuse not to provide people living with HIV selenium supplements as complementary therapy. The principal reason governments fail to do this is that HIV professionals, the World Health Organization and UNAIDS all cling to a “scientifically impossible”, intellectually indefensible, ethically irresponsible, prematurely conceived, outmoded AIDS paradigm. This paradigm inertia works directly against the interests of the poorest people in the world living with HIV disease. The WHO, UNAIDS and the International AIDS Society should accept that the current AIDS paradigm is scientifically threadbare. It is broken beyond repair and cannot be defended from any solid scientific point of view. It does not begin to explain all the relevant phenomena. This serious failure in scientific conceptualization hurts millions of people with HIV worldwide. It is past time to think outside the box and shift the AIDS causation paradigm to a more defensibly moral and scientific position that can save lives, improve the health of millions, and save governments billions of dollars in health care cost.      

                                                                                                7 April 2019, revised 31 January 2023

References

1.      The importance of selenium to human health. Margaret P. Rayman, Lancet;356:233-241

2.      High risk of HIV-related mortality is associated with selenium deficiency. Marianna K. Baum et.al., Journal of Acquired Immune Deficiency Syndrome and Retrovirology 1997;15:370-374

3.      Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase. Vadim Gladyshev, Proceedings of the National Academy of Sciences (USA) 1999; 06: 835-839

4.      Mortality risk in selenium-deficient HIV-positive children. Adriana Campa et.al., Journal of Acquired Immune Deficiency Syndrome and Retrovirology 1999;20:508-513

5.      The role of selenium as adjunct to HAART among HIV-infected individuals who are advanced in their disease. N.N.Odunukwe et.al., AIDS 2006 – XVI International AIDS Conference, Abstract no. MOAB0403

6.      Effect of selenium supplementation in CD4 T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial. Julius Kamwesiga et.al., AIDS 2015;29:1045-1052

7.      The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities. Zhi Huang et.al., Antioxidant and Redox Signaling 2012;16:7:705-743