AIDS Denialism Was Rejected Long Ago. It May Be Back

Pseudoscience has recently been rampaging in the US. While much of it concerns vaccines, an "oldie" is again making the rounds: the myth that HIV is not the sole cause of AIDS. This nonsense has been dormant for a while, but it is once again "up for debate." Not, however, in the world of educated people. Here is a look at the irrefutable evidence that should put this to rest. But will it?

While much of the growing antiscience movement in the U.S. has centered on vaccine misinformation, a possibly more insidious claim—the denial that HIV causes AIDS—has resurfaced. If such denialism gains traction, it could pose a greater public health risk than vaccine skepticism. (1)

The evidence of the causation of AIDS by HIV is both personal and overwhelming. I was doing research on AIDS-related opportunistic infections during the time that many life-saving drugs were becoming available and I can say with absolute certainty that when HIV replication is suppressed to undetectable levels, transmission does not occur. Make no mistake: Undetectable = untransmittable. It's that simple.

To put this in perspective, the lower limit of detection of HIV, as measured by the number of HIV RNA "particles" in 1 mL of blood (also called the viral load or copies/mL) ranges from 20-50 copies per mL, depending upon the assay being used. At or below this level, HIV cannot be detected or transmitted from one individual to another. Contrast this with viral loads ranging from 100,000 to several million copies detected during an active infection. In no way can it be a coincidence that when HIV RNA is virtually undetectable transmission ceases, or that when the viral load is high the virus is highly transmissible. 

Let's take a look at some other evidence.

Epidemiological Evidence

Epidemiological studies conclusively prove both correlational and causal evidence linking HIV to AIDS. The first AIDS cases emerged in 1981, initially among gay men, later intravenous drug users and hemophiliacs. All three groups experienced immune system failure making them susceptible to opportunistic infections like Pneumocystis pneumonia and Kaposi’s sarcoma; conditions that are rare in people with healthy immune systems. 

HIV was detected in all three groups confirming it as the underlying factor behind their immune collapse. Finally, HIV can be consistently isolated from people with AIDS but not from uninfected individuals. In contrast, there is no other virus or pathogen that is universally found in AIDS patients. This rules out the possibility of another infectious agent, something that some AIDS deniers continue to argue.

Evidence at the molecular level

There are seven classes of drugs that inhibit HIV replication. Of the ~50 approved AIDS drugs (3) that target distinct stages of the HIV life cycle, each has a well-characterized molecular mechanism that prevents or treats AIDS symptoms.  The molecular mechanism for all of them is fully known and every one of them either treats or eliminates the symptoms of AIDS. Given that so many different drugs that operate by known (but distinct) mechanisms "just happen" to treat or prevent AIDS proves beyond a shadow of a doubt that HIV is the causative agent of AIDS. Furthermore, the mechanisms of inhibition all coincide with different stages in the HIV life cycle (Figure 1). When these processes (also called targets) are inhibited there is a corresponding upturn in the immune system. More on this later. 

Figure 1. Three different HIV life cycle steps aka targets, are shown at the molecular level. (Left) The X-ray crystal structure of an HIV-protease inhibitor bound to the active site of the enzyme. (Center) The X-ray crystal structure of an HIV reverse-transcriptase inhibitor bound to the enzyme HIV reverse transcriptase. (Right) An electron micrograph below shows new (progeny) HIV particles budding from an infected H9 cell (2).  Source: Wikimedia Commons, ASM Journals, Expert Opinions on Therapeutic Patents

Mother-to-child transmission

Babies born to HIV-positive mothers have a very high risk of developing AIDS unless they receive antiretroviral therapy, but HIV-negative mothers do not give birth to children who develop AIDS. Likewise, when HIV+ mothers are treated with HAART drugs (3) and are below detectable levels of the virus, none of their babies are born HIV+.

HIV attacks and destroys immune system cells

HIV has been isolated, and studied; its presence is the cause of immune system collapse. Here's how it works.

(Left) Electron micrograph of HIV-1 (in green) budding from a cultured lymphocyte. Multiple round bumps on the cell surface represent sites of assembly and budding of virions. Image: Wikimedia Commons. (Right) A simplified diagram of the HIV life cycle. Source: Wikimedia Commons

A subset of white blood cells called CD4+ T cells (also known as helper T cells) is a critical component of the immune system. HIV targets these cells by binding to CD4 receptors, which allows the virus to enter and replicate, producing thousands of new virus particles that burst out of the cell, killing it. As the infection progresses and CD4+ cell levels decline, the immune system becomes increasingly dysfunctional. AIDS is diagnosed when the CD4 count falls below 200 cells/µl. The profound impact of HIV-mediated destruction on immune function is undeniable.

Clinical evidence of the efficacy of Highly Active Antiretroviral Therapy (HAART)

If HIV causes AIDS, then blocking HIV replication must prevent or delay AIDS progression— exactly what has been observed in millions of cases. The utility of HAART drugs provides strong evidence that HIV is the causative agent of AIDS:

HAART reduces HIV viral load, often to undetectable levels, preventing disease progression. These patients do not develop AIDS. With consistent treatment with the most effective drugs, individuals with HIV can now live nearly as long as those who are not infected. Before the introduction of HAART, most people with HIV developed AIDS symptoms and succumbed to the disease within 5 to 10 years. 

Moreover, if patients stop HAART, their viral load will rebound, CD4 counts will decline, and AIDS-related illnesses will emerge. But when HAART is reinitiated, immune function is restored, clearly demonstrating the direct role of HIV in immune system damage.

HIV drugs prevent infection

HAART drugs do not simply treat HIV infection. They prevent it. This is called Post-Exposure Prophylaxis (PEP) or Pre-Exposure Prophylaxis (PrEP)

PEP is given after potential exposure to HIV to prevent infection. PrEP is taken before exposure to reduce the risk of contracting HIV. Individuals who take PrEP do not develop AIDS, demonstrating that blocking HIV infection effectively prevents the progression to AIDS.

 Koch’s Postulates

Beyond clinical and molecular data, Koch’s Postulates—long used to establish causation in infectious diseases—further confirm HIV as the sole cause of AIDS. There are four criteria to determine whether a specific microorganism causes a disease. They are:

1. The microorganism must be present in all cases of the disease but absent in healthy individuals.
2. The microorganism must be isolated and grown in pure culture.
3. When introduced into a healthy host, the cultured microorganism must cause the same disease.
4. The microorganism must be re-isolated from the newly infected host and identified as the same pathogen.

Koch’s Postulates unambiguously confirm HIV as the cause of AIDS.

1. HIV is found in all AIDS patients.
2. HIV can be isolated and grown in culture.
3. Introducing HIV into animal models (or infection of people) causes an AIDS-like disease.
4. HIV can be isolated from all people who have AIDS (and infected animals)

All four Koch postulates are met, making HIV the confirmed cause of AIDS.

Bottom line

Since the US may be on the precipice of a resurgence of pseudoscience, it is more crucial than ever to define and defend facts. It is a fact that HIV is the cause (and the only cause) of AIDS. Anyone who doubts or denies this, given the wealth of evidence in support of the claim, should to be ignored and shunned.

NOTE:

(1) There has been some recent confusion (here, and here) where lenacapavir (Sunlenca) was referred to as a vaccine (It is not). If this incorrect information spreads and lenacapavir is subjected to anti-vaccine hysteria the toll on African women could be enormous.

(2) H9 cells are a type of CD4+ T-cell (a type of white blood cell that is part of the immune system) commonly used in HIV research. They serve as a validated model for studying viral replication, drug testing, and immune response in cell cultures.

(3) About half of these drugs consist of unique molecules. The rest are combinations of two or more of these drugs.