HIV Cure: Trial and Error Sheds New Light

By: Ranier Simons, ADAP Blog Guest Contributor

According to the World Health Organization (WHO), at the end of 2021, about 38.4 million people globally were living with HIV/AIDS.[1] Medical science has advanced through the years, creating novel treatments for many illnesses, eradicating diseases from the global population, and finding cures for others. However, a permanent cure for HIV remains elusive. Researchers have recently announced a fifth person that has been cured of HIV. While the news is exciting and further adds to knowledge about the virus, the mechanism of the cure is not scalable. Additionally, it is important to note that a promising HIV-vaccine also recently failed advanced-stage clinical trials. 

Photo Source: Scientific Scarsdalian

A 53-year-old man, known as the "Dusseldorf patient", is the fifth and latest person to be cured of HIV due to a blood stem cell transplant.[2] This is the exact mechanism by which four other people have been cured of HIV. This man and the others received a blood stem cell transplant as an aggressive late-stage effort to treat leukemia. 

In 2013, doctors destroyed the patient's cancerous bone marrow and subsequently healthy bone marrow as well and replaced it with donor stem cells from a person who had a mutation that rendered them resistant to HIV infection.[3] The mutation was in the genes for the CCR5 receptor, a receptor HIV needs to enter immune cells. The mutation prevents the CCR5 receptor from being expressed on the surface of immune cells. The transplanted stem cells grew and replaced the old bone marrow, giving the patient a new HIV-resistant immune system. In 2018, the Dusseldorf patient stopped taking ART and has remained HIV-virus-free.[3]

The first person to be cured of HIV/AIDS as a result of a stem-cell transplant to treat blood cancer was Timothy Ray Brown in 2007. He was known as the "Berlin patient", and his cure was confirmed in 2009. Another patient, the "London patient", was reported as being cured in 2019. A 63-year-old man known as the "City of Hope" patient and a woman known as the "New York patient" were reported in scientific literature in 2022 as being cured. The "City of Hope" patient, thus far, has been the person who has lived with HIV the longest. At one point in his HIV journey, he had an AIDS diagnosis, having had HIV since 1998.[4] 

Unfortunately, blood stem cell transplantation is not a scalable solution, and it is only used in extreme cases for people battling blood cancers with no other options. It cannot be used as a cure for all patients living with HIV because the risks are too significant. It is not guaranteed to work and is very dangerous since it requires wiping out a person's entire immune system, and that state leaves a patient open to infections with no protection. Additionally, it is possible a person's body could reject the donor stem cells as well.

Photo Source: POZ Magazine

January 2023 also brought news of a failed HIV-vaccine clinical trial. The Mosaico Study, a phase 3 clinical trial conducted by the HIV Vaccine Trials Network(HVTN), was ended due to the results of an interim review.[5] The Mosaico Study vaccine was what is known as a 'mosaic vaccine.' This means that it contains genetic material from a variety of HIV strains prevalent worldwide to trigger a broad immune response.[5] The study focused on cisgender men and transgender people who have sex with cisgender men and/or transgender people from around the world. The failure of the trial was reported when it was found that the vaccine was ineffective in preventing infections compared with the placebo.[6]  Over the past 40 years, clinical trials on HIV vaccines have reached phase 3 only eight times.[6] All have failed.

A significant factor in why HIV is so challenging to cure is how it operates. When HIV enters the body, some of the immune cells it infects are long-lived immune cells that soon become latent. Those sleeping cells can stay dormant for years. While those infected immune cells are dormant, they are not replicating HIV. Antiretroviral therapies target infected cells that are actively replicating new copies of HIV. Thus, the "sleeping cells" are not being targeted. The latent or "sleeping" cells are what scientists refer to as HIV reservoirs in the body. Those infected cells can wake up and become active at any time. That is why it is essential to be consistent with antiretroviral adherence. 

We may not have a cure for HIV/AIDS. However, the disappointing vaccine trials and the science learned from the extreme stem cell transplants are still valuable and push us closer to conquering the virus. Trial and error will eventually produce powerful tools to beat HIV/AIDS.

[1] World Health Organization. (2023). HIV. Retrieved from https://www.who.int/data/gho/data/themes/hiv-aids#:~:text=Globally%2C%2038.4%20million%20%5B33.9%E2%80%93,considerably%20between%20countries%20and%20regions

[2] Sathyakumar, K. (2023, February 20). 5th person confirmed to be cured of HIV. Retrieved from https://abcnews.go.com/Health/5th-person-confirmed-cured-hiv/story?id=97323361

[3] Reardon, S.(2023, February 21). Third patient free of HIV after recieving virus-resistant cells. Retrieved from https://www.nature.com/articles/d41586-023-00479-2

[4] Marquez, L.(2022, July 27). Patient achieves HIV and blood cancer remission three decades after HIV diagnosis through stem cell transplant at City of Hope. Retrieved from  https://www.cityofhope.org/patient-achieves-hiv-and-blood-cancer-remission-three-decades-after-hiv-diagnosis-through-stem-cell#:~:text=Known%20as%20the%20City%20of,is%20now%2066%20years%20old

[5] Fred Hutchinson Cancer Center. (2023, January 27). Phase 3 Mosaic-Based Investigational HIV Vaccine Study Discontinued Following Disappointing Results of Planned Data Review. Retrived from https://www.hvtn.org/news/news-releases/2023/01/phase-3-mosaic-based-investigational-hiv-vaccine-study-discontinued-following-disappointing-results-planned-data-review.html

[6] Loewy, M. (2023, February 13). Researchers Voice 'Frustration' at Failed HIV Vaccine Trial. Retrieved from https://www.medscape.com/viewarticle/988191#vp_1

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.  

What is 100-100-100?

By: Ranier Simons, ADAP Blog Guest Contributor

The ongoing Covid-19 pandemic is a glaring reminder of the importance of the global efforts to address other epidemics and pandemics. After over 30 years of such efforts, worldwide there has been success with polio. Wild poliovirus was virtually extinct in 2020 with only about 140 cases remaining.[1] However, two serious remaining global disease crises are HIV/AIDS and Hepatitis C (HCV).

In 2020, it was estimated that there were 37.7 million people living with HIV/AIDS, and an estimated 58 million people with chronic Hepatitis C.[2][3] The strongest two-pronged approach to fight both is testing and treatment. In 2014, UNAIDS, the Joint United Nations Programme on HIV/AIDS, came up with a target known as 90-90-90. The goal was to have 90% of all persons living with HIV/AIDS aware of their status, 90% of all diagnosed on sustained antiretroviral treatment, and for 90% of those on treatment to have an undetectable viral load by 2020. 

The WHO, World Health Organization, proposed a similar target for HCV in 2016. They pledged to globally eliminate HCV by 2030. This elimination included a target of 80% those with HCV to be in treatment, a 90% reduction in new infections, and a 65% reduction in liver-associated deaths as a result of hepatitis C.[4] 

Photo Source: UNAIDS

The 90-90-90 goal was not met in 2020 and it is not likely that HCV will be eradicated by 2030. Were the goals too ambitious or was there something missing in the execution of the efforts? 

The focus has always been on testing and treatment. It is of the utmost importance to have widespread testing to identify those that need treatment in order to get them into treatment. However, what had previously been missing was discourse on barriers to testing and treatment. In 2021, the UNAIDS Global AIDS Strategy acknowledged the existence of structural barriers to HIV and HCV testing and services. 

The challenge has been that solving the problem of these hurdles has not been included in the system of testing and treatment. The structural hurdle of lack of fulfilment of basic needs should be a systemic part of treatment. Human nature prioritizes stable shelter, food, and safety over seeking out testing and adherence to treatment regimens.

This is especially true in the population of people who inject drugs (PWID). Intravenous drug users are 29% more at risk to contract HIV and 40% of new HCV infections worldwide.[5]

Photo Source: Yahoo!

In response to understanding the importance of including the effective meeting of basic needs as part of disease prevention, a new target, 100-100-100 is being discussed in global health circles. It is initially being considered through the lens of PWID regarding HIV and HCV. The goal is to have stable housing for 100% of PWID who have housing instability, offering substance abuse treatment to 100% of PWID that desire treatment, and giving 100% of PWID access to harm reduction services.

Stable housing means safe and consistent shelter. It means having a stable place to eat and prepare meals. Having stable housing provides a place for self-care and identity.  Stress is lowered when one has a safe stable place to live as well allowing focus on other needs. A sense of community results from stable housing as well. When groups of PWID have stable housing, they can create a sense of belonging and care for each other communally. 

Having a stable place to live and rest also facilitates successful substance abuse treatment. Taking away stressors of basic survival allows a person to redirect their energies towards bettering their lives. Coupled with substance abuse treatment is harm reduction. Harm reduction services come in many forms.[6] Most importantly it is acknowledging the complicated etiology of drug use. It is the realization that drug use does happen, and it is necessary to help people along the continuum of complete abstinence from drug use to the other end of safer and “responsible” drug use starting at whichever stage PWID find themselves.

Reaching this 100-100-100 goal, along with aggressive strides toward testing and treatment, is the growing discourse that is providing hope towards the eradication of HIV and HCV. Removing the inequalities of lack of basic needs will help not just PWID but the greater population at large living with HIV and HCV as well.

[1] Kaiser Family Foundation. (2021, Oct 29). The U.S. Government and global polio efforts. Retrieved from https://www.kff.org/global-health-policy/fact-sheet/the-u-s-government-and-global-polio-efforts/
[2] UNIADS. Global HIV and AIDS statistics fact sheet. Retrieved from https://www.unaids.org/en/resources/fact-sheet
[3] World Health Organization. (2021, Jul 27). Hepatitis C. Retrieved from https://www.who.int/news-room/fact-sheets/detail/hepatitis-c
[4] World Health Organization. (‎2016)‎. Global health sector strategy on viral hepatitis 2016-2021. Towards ending viral hepatitis. World Health Organization. Retrieved from https://apps.who.int/iris/handle/10665/246177
[5] UNAIDS. (2017, Jan 1) 90–90–90: an ambitious treatment target to help end the AIDs epidemic. Retrieved from https://www.unaids.org/en/resources/documents/2017/90-90-90
[6] Principles of harm reduction. National Harm Reduction Coalition. Retrieved from https://harmreduction.org/about-us/principles-of-harm-reduction/ 

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.

How Americans could unknowingly end up taking black market drugs

By: Brandon M. Macsata, CEO, ADAP Advocacy Association

Senators Chuck Grassley (R-IA) and Amy Klobuchar (D-MN) recently introduced a bill that would permit Americans to import pharmaceuticals from Canada. The two lawmakers believe their bill will reduce drug costs.[1] But their effort begs the question: at what cost?

The bill would instead expose patients to potentially dangerous counterfeit drugs. Lawmakers would be wise to vote against it.

Photo Source: impactlab.net

Americans currently have the safest pharmaceutical supply chain in the world. In large part, that's thanks to the Food and Drug Administration, which strictly supervises the manufacturing and transport of medicines. About 60 percent of our drugs are manufactured at high-tech, ultra-safe facilities right here in the United States.[2] The remainder are made in foreign factories but shipped into the United States through trusted vendors, who never allow the medicines to leave their control.

Sens. Grassley and Klobuchar's bill would allow people to purchase drugs that didn't go through this tightly controlled supply chain. That's worrying. No matter its rigorous safety precautions at home, the FDA can't vouch for the safety and efficacy of foreign-made and supervised drugs. That’s a pretty high price to pay for cheaper drugs.

This is particularly concerning when it comes to drugs coming in from Canadian pharmacies, which often resell drugs imported from India, Turkey, and other countries with subpar safety standards.[3][4]  In fact, one FDA investigation found that 85 percent of packages imported to the United States from online Canadian pharmacies contained potentially counterfeit drugs.[5] One in 10 drugs from low and middle-income countries is fake or substandard, according to the World Health Organization.[6] Some are laced with deadly ingredients, like boric acid and fentanyl.[7]

I've experienced firsthand the dangers of foreign drug imports. I was diagnosed with HIV just shy of my 30th birthday.[8] That day, I found out I was destined to undergo antiretroviral therapy for the rest of my life.[9]

But when my out-of-pocket costs hit $1,300 in just my second month of treatment, I started looking for a cheaper option. I began ordering my medicine from an online pharmacy in Canada.[10]

It never crossed my mind that I might have been taking counterfeit medicine, or that the medicines meant to control my HIV could be compromising my immune system. So when my doctor found out, she told me to stop immediately. She warned me that online pharmacies often sell counterfeit drugs.

Government officials have long opposed importation policies for the same reason.

Photo Source: The Partnership for Safe Medicines

Former FBI Director Louis J. Freeh warns that "importation proposals would do nothing but shift the costs and burden to law enforcement and open up the U.S. drug supply to adulterated and counterfeit drugs."[11]

Former FDA associate commissioner Peter Pitts, meanwhile, opposes the Grassley-Klobuchar proposal for the same reason. He adds that the bill "could endanger American lives by opening the floodgates to harmful counterfeit drugs."[12]

Four other past FDA commissioners penned a letter to Congress explaining that importation would "harm patients" and "compromise" the United States' "carefully constructed system."[13]

And former HHS Secretary Mike Leavitt echoed similar concerns, writing that, while in office, it was "impossible… to certify that importation of medicines from unregulated sellers is safe."[14]

They're all right.

For nearly two decades, liberal and conservative officials have warned against the dangers of drug importation. Not a single FDA commissioner or HHS secretary has been able to verify that it's safe.  Let's listen to the experts -- importation is not a risk worth taking.

This opinion piece was also published in the March 6th edition of the Times of Northwest Indiana.

__________
[1] https://www.grassley.senate.gov/news/news-releases/grassley-klobuchar-introduce-legislation-permit-personal-importation-rx-drugs 
[2] https://www.consumerreports.org/cro/news/2014/04/are-generic-drugs-made-in-india-safe/index.htm:  "About 40 percent of the medications Americans use everyday are made outside the U.S."
[3] https://www.safemedicines.org/2015/10/5-secrets-canadian-pharmacies-dont-want-you-to-know.html 
[4] http://www.safemedicines.org/wp-content/uploads/FDA-Operation-Reveals-Many-Drugs-Promoted-as-_Canadian_-Products-Really-Originate-From-Other-Countries-captured-January-2017.pdf 
[5] https://www.hivplusmag.com/treatment/2016/7/01/how-avoid-black-market-hiv-drugs 
[6] https://www.reuters.com/article/us-pharmaceuticals-fakes/tens-of-thousands-dying-from-30-billion-fake-drugs-trade-who-says-idUSKBN1DS1XJ 
[7] https://www.safemedicines.org/2015/11/poisons.html 
[8] https://www.washingtonblade.com/2017/08/11/opinion-buying-medicines-online/ 
[9] https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/51/hiv-treatment--the-basics 
[10] https://www.washingtonblade.com/2017/08/11/opinion-buying-medicines-online/ 

[11] https://storage.googleapis.com/m1738/20170605_Report%20on%20Counterfeit%20Drugs.pdf (page 5)

[12] https://www.safemedicines.org/2019/01/importation-is-too-risky-warns-former-fda-associate-commissioner.html and https://thehill.com/opinion/healthcare/426615-proposed-drug-importation-bill-would-expose-americans-to-counterfeit-meds

[13] https://www.washingtonpost.com/news/to-your-health/wp/2017/03/17/four-former-fda-commissioners-denounce-drug-importation-citing-dangers-to-consumers/?utm_term=.c21f7b053dab 

[14] https://morningconsult.com/opinions/drug-importation-flawed-policy/ 

[15] https://www.safemedicines.org/2018/07/who-opposes-drug-importation-every-head-of-the-fda-and-hhs-since-2000.html 

Drug Importation Policy is a Hard Pill to Swallow

By: Brandon M. Macsata, CEO, ADAP Advocacy Association

When I first heard the news that Congress was considering legislation that would allow prescription drugs to be imported from abroad, I was honestly quite shocked. I know firsthand how such policy can negatively impact consumers who decide to purchase drugs from abroad. The potential consequences are quite daunting.

In 2002 (just shy of my 30th birthday), I was diagnosed with HIV. When my doctor told me the news, a hundred questions came to mind all at once. What was my long-term prognosis? What types of medications would I have to take? Who could I turn to with my questions about life with HIV?

(Editor's Note: The photo of me was taken in 2002 on Easter Sunday during the time that I was importing my HIV medications. At the time, I was still quite sick after experiencing my acute seroconversion. In fact, in this photo my two best friends are literally helping me stand up, and they made me look "presentable" with some make-up. The benefits of rooming with two wonderful women who took care of me.)

What happened next directly shaped my viewpoint of the dangers associated with importation.

I ordered medications from an online Canadian pharmacy. To this day, I have no way of knowing where the drugs were made or if they contained the active ingredients I needed to effectively treat my condition.

At the time, I opted not to consult my physician in the process. Due to my insurance coverage, my out-of-pocket cost was $1,300 during the second month of treatment. For two months, I received medications via mail from Canada. Honestly, I didn’t even entertain the idea of whether the medicines were real or fake.

Fortunately, my doctor intervened and advised me of the reality of what I was doing. She told me that drugs purchased through online channels are often counterfeit and most likely do not contain any ingredients that help patients. In many cases, the ingredients can be deadly. Without even knowing it, I was rolling the dice with my health and safety. It was an eye opening intervention and one that too few patients ever experience before irreparable damage has been done.

Without question, we need to address the issue of rising health care costs in the United States, which greatly contributes to patients buying medicines online. However, legalizing importation isn’t the solution we need. It will undoubtedly lead more patients to risk their health and, ultimately, their lives through online drug purchases.

Consider the following: The World Health Organization estimates that 10 percent of medicines across the world are fake. In some parts of the world, this number is as high as 30 percent. In 2015, Interpol confiscated nearly 21 million fake medicines, a significant increase over the previous year.

As a society, why would we take our guard down when the threat is so high? As someone who is informed on health care issues (even at the time of my diagnosis), my search for Canadian pharmacies did little to warn me against the dangers. I had little knowledge or available information when I ordered medications from Canada.

Rather than open the floodgates to unregulated medicines, we should be doing more to ensure the safety and integrity of our drug supply. Last month, former FBI Director Louis Freeh released a report highlighting the incentives that drug importation would create for criminals who are actively marketing to consumers in the U.S. and the burden it would place on law enforcement who protect our drug supply.

Among his recommendations to be proactive on the issue, Mr. Freeh urges policymakers to conduct a detailed assessment of law enforcement’s readiness and ability to get in front of the threat that exists. I completely agree with Mr. Freeh - this should be our focus.

As we strengthen our defenses, we must also prioritize patient education and engagement initiatives to ensure that we’re deterring importation from the moment of diagnosis. The reality is that a number of online pharmacies with a Canadian flag attached to them are merely front doors for smugglers operating in countries across the globe.

There are viable ideas to combat the rising cost of healthcare – including prescription medications – but importation is not one of them.

Over the past two decades, we’ve made significant progress against HIV/AIDS. Today, there are medications available that we didn’t have just a few years ago. In fact, recent studies have shown that people in North America and Europe who are infected with HIV and who begin treatment with a triple-drug cocktail can expect to live nearly as long as people who aren’t infected by the virus.

Having lived with HIV for nearly 15 years, I know how important medicine is in achieving a sense of normalcy again. If we embrace drug importation, we’re sending a signal to patients across the country that their health and safety don’t matter. Lawmakers should not be playing a game of chance when patient lives hang in the balance.

This opinion piece was also published in the August 11th edition of the Washington Blade.