Are Plant-Based HIV Drugs on the Horizon?

From the earliest days of the HIV epidemic, scientists have looked into the use of plant extracts to treat HIV infection. Many of the earliest studies focused on the antiviral properties of certain plants, specifically their ability to kill HIV while remaining safe (or at least relatively safe) for human consumption.

Lab worker using a microscope
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Today, much of this branch of science has been centered around the use of certain plant extracts to interfere with HIV’s ability to replicate, much in the same way that antiretroviral drugs work. Some of these extracts have been used for generations in traditional cultures to treat a wide range of illnesses and medical conditions.

While most of these studies have had limited success, a team of researchers from the University of Illinois at Chicago has claimed to have found a plant, called Justicia gendarussa, which is able to block HIV, in their words, "much more effectively than AZT." It’s a bold claim given that the drug AZT (also known as Retrovir and zidovudine) had long been the cornerstone of HIV therapy.

But do these claims actually hold up, and, more importantly, do they translate to a new "natural" model of HIV treatment?

A Short History of Plant Extracts in Early HIV Research

When HIV was first discovered, people infected with the virus had few options for treatment. In fact, it wasn’t until March 1987—a full five years after the first cases of HIV were identified—that AZT was finally approved for use in treating HIV. Unfortunately, as the first and only drug, it didn’t work all that well, and people would have to wait another eight years before the second drug, lamivudine (3TC), would be approved in 1995.

During this 13-year window, many individuals and unsanctioned buyer’s clubs turned to traditional remedies to either complement AZT therapy or treat HIV on its own without the fear of toxic side effects. Some of the earliest plant-based studied focused on these remedies, hoping they could either "boost" a person’s immune function, prevent opportunistic infections, or kill HIV outright.

These included studies involving laetrile, a purported cancer cure derived from apricot pits, and Asian bitter melon (Momordica charantia), which some scientists had suggested could restore immune function while battling HIV-associated respiratory infections.

While many hopes had been pinned on these and other natural cures, none showed any real benefit and were really "shots in the dark" triggered by increasing public desperation to find a treatment, any treatment, that might work.

From Folk Medicine to Clinical Research

By 1996, even as more effective drugs were being released and combination therapies began to turn back the tide of AIDS deaths, there remained many in the research community determined to find natural alternatives to the sometimes highly toxic drugs (such as stavudine and didanosine) being used in HIV therapy.

Many of these efforts focused on the various plants and herbs used in traditional cultures, investigating both their safety and efficacy in a more structured clinical research model. Typically, the results fell short.

One review of traditional Chinese medicines concluded that none of the popular remedies used to treat HIV infection (such as jingyuankang and xiaomi) had any effect on a person’s CD4 count or viral load (although some did provide relief for such minor infections as oral thrush and uncomplicated diarrhea).

Similar studies investigated the use of the African potato (Hypoxis hemerocallidea) and a medicinal plant called Sutherlandia frutescens, both of which had been approved by the South African government to treat HIV. Not only did the remedies not work, but they were also shown to be antagonistic to some of the medications used to treat HIV-associated illnesses like tuberculosis.

While it would be easy to dismiss these remedies as "folk medicine" (or even contrarian science), the setbacks in plant-based research, some argue, have been no less profound than those seen in HIV vaccine research wherein billions have been spent with no viable candidate to date.

Re-Thinking the Therapeutic Model

The field of plant-based HIV research has changed enormously with access to genetic tools that weren’t even around 20 years ago. Today, we have a far greater understanding of the very mechanics of HIV—how it replicates, how it infects—and can better identify which processes we need to interrupt to render the virus harmless.

It is much the same model used with antiretroviral therapy wherein a drug interferes with a specific enzyme needed to complete the HIV replication cycle. Without the ability to do so, HIV cannot spread and infect other cells. By using a combination of the drugs—each with the ability to block a different enzyme—we are able to suppress the virus to so-called undetectable levels.

In recent years, a number of plant extracts have been able to replicate this process, at least in the test tube. Some of these include Cistus incanus (pink rock rose) and Pelargonium sidoides (South African geranium), both of which appear to prevent HIV from attaching to a host cell.

As far-fetched as all of this may sound—using a geranium to treat HIV—it is a model that, in fact, already has its proof-of-concept in malarial disease.

Plant-Based Malaria Breakthrough Offers Proof-on-Concept for HIV

Much of the rationale for current plant-based research hinges on a malaria breakthrough which garnered its discoverer, Chinese scientist Tu YouYou, the Nobel Prize in Medicine in 2015.

The discovery was based on the research of plant called Artemesia annua (sweet wormwood) which has been used in Chinese medicine since the 11th century. In the early 1970s, Tu YouYou and her colleagues began exploring the effects of the plant (known traditionally as qinghao) in malaria-causing parasites.

In the course of the ensuing years, the scientists were able to gradually refine the extract to a compound called artemisinin which today is the preferred treatment of choice when used in combination therapy. Artemisinin has not only been shown to wipe out 96% of drug-resistant malarial parasites, but it has also been credited with saving millions of lives that might have been otherwise lost to the disease.

Medicinal Extract Proves "Better Than AZT"

Riding on the promise of a similar artemisinin breakthrough, a cohort of scientists from the University of Illinois at Chicago, Hong Kong Baptist University, and the Vietnam Academy of Science and Technology began a cooperative effort to screen of more than 4,500 plant extracts, evaluating their effect against HIV, tuberculosis, malaria, and cancer.

Of these candidates, an extract derived from Justicia gendarussa (willow-leaf justicia) was considered the most promising. Purification of the extract led to the isolation of a compound known as patentiflorin A which, in test tubes, was able to block the same enzyme (reverse transcriptase) as AZT.

In fact, according to the research, it was able to improve on AZT’s action in a number of ways:

  • Patentiflorin A appears more effective in blocking replication in drug-resistant HIV. AZT, by comparison, has a low resistance profile, meaning that even some of the more common HIV mutations can render the drug useless. As such, patentiflorin A would seem to have a better resistance profile.
  • Patentiflorin A was able to do the same in macrophages, the white blood cells which serve as the body’s first-line defense. This is important because macrophages are the cells that trap and carry bacteria and viruses to the lymph nodes for neutralization. With HIV, this doesn’t happen. Instead, the virus "turns the tables" and infects the very cells (called T cell lymphocytes) meant to aid in their destruction. It is suggested that by suppressing the virus in early infection—and in the macrophages themselves—it may possible to avert infection altogether.

At least that is how it reads in the test tube.

Significant Barriers to Overcome

While there is no doubt that patentiflorin A is a significant, and even promising, candidate for further research, it is rare that the results from a test tube study mirror those in human trials. Moreover, while the contention that patentiflorin A is "better than AZT" may be accurate, it may not be as relevant as the researchers (or some in the media) are suggesting.

Quite simply, AZT is an old drug. It is the first of the eight drugs in its class and one that has been largely supplanted by newer generation drugs like tenofovir and abacavir. As such, using AZT as the baseline of comparison is rather like comparing an old VW Beetle to the new VW Beetle. They both work, but you wouldn’t necessarily characterize the fleet by its oldest model.

And that’s part of the point. Ultimately, the goal of any plant-based therapy would need to achieve the same level of effectiveness as its pharmaceutical counterpart or to at least enhance its effect. In order to do this, a plant-based candidate like patentiflorin A would have to overcome a number of key obstacles:

  • It would have to reach a therapeutic concentration in the blood. After all, it’s one thing to expose cells to a compound in a test tube; it’s another to ingest that compound and have enough active ingredient circulating in the bloodstream. Since plant extracts are typically expelled from the body quickly, scientists would have to create a concentrated formulation able to achieve a therapeutic effect while avoiding toxicity.
  • It would need to be able to cross the membranes of the intestines. Most plant extracts are water-soluble and have great difficulty crossing the lipid membranes of the intestines. Reduced absorption translates to lower bioavailability (the percentage of drug entering the bloodstream).
  • It would need to be maintained at constant levels in the blood. HIV drugs aren’t like antimalarials, which aim to kill the parasite and be done with it. With HIV therapy, a certain drug concentration must be maintained at all times to keep the virus fully suppressed. Since plant extracts are expelled quickly, they are prone to fluctuations that may be inappropriate for HIV. Artemisinin, for example, has a drug half-life of only two to four hours compared to tenofovir which has a half-life of 17 hours and an intracellular half-life of up to 50 hours.

While there are a number of tools researchers can use to overcome absorption problems (like lipid-based delivery systems), unless they can overcome the bioavailability problems seen in plant-based drugs like artemisinin, it is less likely they’ll be anything more than a supportive therapy.

A Word From Verywell

What makes a plant-based approach attractive to us, at least from a conceptual point of view, is that the substances are not only natural but have been used safely for generations. But it also presumes that plant-based therapies are "more safe" and HIV drugs are more "more toxic," and that isn’t necessarily so.

The HIV drugs we used today are not without their side effects, but they are far improved for those of the past. They are not only more tolerable, but they also require as little as one pill per day and are far less prone to drug resistance.

So, while every effort should be made to advance the plant-based HIV research, there is still a lot to overcome before we can reasonably consider them options for the future.

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