Fraudsters Target Medicine being Reimbursed at a Loss for Counterfeit Crime

By: Ranier Simons, ADAP Blog Guest Contributor

Pharmacy Benefit Managers (PBMs) don’t make medicine or dispense medicine, but their business decisions determine what medicines you have access to. Some of those decisions are now creating openings for drug counterfeiters to enter the legitimate supply chain, according to a report by the Partnership for Safe Medicines (PSM) and subsequent analysis by the Community Access National Network (CANN). This is a pressing matter because counterfeit drugs can result in adverse side effects, treatment failure, resistance, toxicity, and death.[1]

Photo Source: Center for Medical Economics & Innovation

The U.S. market value for PBMs in 2023 was $523.9 billion.[2] PBMs have always been marketed to reduce drug expenditures for payers and lower drug costs for patients, but historically, that has not happened. The $523 billion results from questionable practices that bring in sizable profits for PBMs while shortchanging insurance payers with opaque contracts and to the detriment of patients.  Some patient advocacy groups have argued PBMs are harmful to patients’ health. One common PBM practice, below-cost pharmacy reimbursement, creates supply chain contamination opportunities.

Insurance companies reimburse pharmacies for the medications they dispense to patients. A pharmacy purchases medication from a wholesaler and then submits a claim to a patient’s insurance to be paid for the medication. PBMs handle the payments to the pharmacies on behalf of insurance companies. In 2023, 332 million people in the U.S. had health insurance, and 275 million of them were served by Pharmacy Benefit Managers (PBMs) via commercial insurance, Medicare Part D, Managed Medicaid, and Medicaid Fee-For-Service.[3] Thus, pharmacies are forced to deal with PBMs. In order to dispense medications to patients with insurance, pharmacies must sign contracts with PBMs that are agreements to accept whatever price the PBM dictates for reimbursement. Currently, three PBMs control 75% of the health insurance market; thus, there is no competition.[4] 

The predicament is that PBMs are reimbursing pharmacies below cost. This means that PBMs are paying pharmacies less money than the pharmacies spent to acquire the drugs. Effectively, pharmacies are dispensing drugs at a loss to serve patients. A real-world example of one of the big three PBMs' contracts with a pharmacy for brand-name drugs listed reimbursement of the average wholesale price (AWP) minus 25.5% + $0.00. The same contract listed AWP minus 57% + $0.00 for generics. 

The following examples are actual claims submitted by pharmacies and their resulting losses based on the PBM contracts. For Biktarvy, a pharmacy acquired a 30-day wholesale supply of the drug for $3700.36, but the PBM only reimbursed $3661.75, resulting in a loss of $38.61. For Genvoya, a pharmacy paid $3,534.78 and was only reimbursed $2,852.92, resulting in a loss of $681.86. A pharmacy in Florida purchased a 30-day supply of roflumilast for $43.86 and was reimbursed by a PBM for $11.22, resulting in a $32.64 loss. PSM has many other examples of losses on other various pharmaceuticals here. 

Photo Source: Partnership for Safe Medicines

The situation is dire, as indicated by a statement given by a pharmacist from an independent pharmacy in Weatherford, Texas: 

“I spent hours on the phone with my wholesaler and even the drug manufacturer trying to explain that we simply cannot sustain such drastic underpayment on this critical medication and every time my concerns fell on deaf ears. After years of trying to affect some kind of change on either the cost or the reimbursement, we simply could not take losses of any kind on a drug that has a price tag of $3000.00. Our losses ranged from $17.46 to $572.30, and we were expected to accept this arrangement from day one. We were a safe haven and trusted health partner for these patients; however, we were forced to notify our patients that we would no longer be able to provide this life-saving medication.”

This pharmacist decided to stop providing the referenced medication. However, all pharmacists do not make that decision, which creates opportunities for criminal exploitation. 

Pharmacists want to do what they can to provide the medicines people need. When they cannot source medications through their prime wholesalers, they turn to the secondary wholesaler market. Secondary wholesalers are also licensed by the state, and many are secure and reputable channels, but this is also where criminals operate. Criminal counterfeiters take advantage of the situation and set up marketplaces for popular, expensive drugs, using black-market diverted or counterfeit products at prices lower than traditional wholesale sources.

Pharmacies do not haphazardly search for and purchase lower-cost medications. They do their due diligence to make sure they are sourcing proper supplies. However, counterfeit criminals have sophisticated and elaborate systems to perpetrate fraud. They sell through companies with legitimate state-issued wholesale licenses and use forged Drug Supply Chain Security Act (DSCSA) transaction tracing histories. A deep dive into the paperwork can reveal the forgery. However, it takes significant resources of time and effort to dig into that kind of tracing. Resources that pharmacies do not have. Thus, when things have the appearance of propriety, pharmacists get duped by criminals, and patients get sold fraudulent medication. 

Photo Source: Partnership for Safe Medicines

In 2022, the U.S. District Court unsealed documents of a civil case in which Gilead Sciences sued a group of criminals. The criminal enterprise distributed over $230 million of counterfeit drugs, some of which were HIV antiretroviral medications.[5] Some of the drugs were diverted, meaning they were purchased from people who had obtained them legitimately and resold on the black market. Some of the drugs were bottles containing medication that did not match what was on the label. Diverted medication indicates that patients were not adhering to their treatment regimens since they were selling their medications. The mislabeled medication bottles meant patients could have been ingesting medications not meant for them, in improper dosages, and possibly contaminated. Situations such as PBM below-cost reimbursement contribute to creating a demand for cheaper medications in an artificially created predatory pricing-induced supply scarcity.

Low PBM reimbursement not only endangers the drug supply chain but also puts independent pharmacies out of business. Pharmacies cannot operate under fiscal loss. In addition to low reimbursement rates, PBMs give pharmacies very low or often zero dispensing fees, which pharmacies need for operating costs. Moreover, PBMs saddle pharmacies with many other opaque fees, audits, and clawbacks, adding to their financial burden. When pharmacies go out of business, patients lose access. This is especially true in areas with very few pharmacies for a large geographical region. If a pharmacy closes, entire communities lose familiar and convenient continuity of care.

A group named Pharmacists United for Truth and Transparency wrote a letter to one of the big three PBMs. A quote from this letter explains what needs to be done: “Reimburse independent pharmacies the full drug acquisition cost and eliminate the practice of reimbursing above some and below other drug costs. Make a fair and universal reimbursement policy the unbreakable operating principle of the PBM-independent pharmacy partnership.” PBM reform is not just fiscally sound; for patients, it indeed could mean the difference between life and death.

[1] Williams, L., McKnight, E. (2014, June 19). The real impact of counterfeit medications. Retrieved from https://www.uspharmacist.com/article/counterfeit-meds#:~:text=The%20use%20of%20substandard%20drugs,enforced%20to%20prevent%20this%20crime

[2] Fortune Business Insights. (2024, April 19). Pharmacy benefit management market. Retrieved from https://www.fortunebusinessinsights.com/pharmacy-benefit-management-pbm-market-103496

[3] Mikulic, M. (2023, May 22). Number of Americans served by PBMs by insurance type 2023. Retrieved from https://www.statista.com/statistics/1172652/pbms-number-of-served-us-persons/

[4] The Partnership for Safe Medicines. (2023) Are below cost reimbursement practices by Pharmacy Benefit Managers creating opportunity for criminals to enter the legitimate supply chain?. Retrieved from https://www.safemedicines.org/2024/02/pbmblackmarket.html

[5] Gilead Sciences, Inc. et al v. Safe Chain Solutions, LLC et al. Retrieved from https://fingfx.thomsonreuters.com/gfx/legaldocs/dwpkrodwdvm/gileand-amended-2022-09-28.pdf?utm_source=Sailthru&utm_medium=newsletter&utm_campaign=daily-docket&utm_term=DailyDocket-MailingList%20v2

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.  

Congress is Knocking on 340B's Door, Saying "Show Me the Money"

By: Ranier Simons, ADAP Blog Guest Contributor

Many members of society are adversely affected by inequalities stemming from diverse circumstances and socio-economic realities. Disparities in public health result from those inequalities. Policy is one avenue for improving the health of those in need. One policy response by Congress was the creation of the 340B Drug Pricing Program as part of the bipartisan Veterans Healthcare Act of 1992.[1] The 340B program allows qualifying safety-net providers and qualifying hospitals, otherwise known as covered entities, to purchase prescription drugs at significantly discounted prices from manufacturers and re-invest those dollars in expanding access to care and treatment. A growing chorus is concerned that the legislative intent of the program is being obfuscated by large hospital systems and mega service providers. 

Photo Source: USA Today

These covered entities serve low-income and vulnerable populations who are uninsured, on Medicaid or Medicare. The savings generated from the program are used to offer patients free or discounted drugs and provide many other services that meet the healthcare needs of the communities these entities serve.[1] Other services include prevention-focused primary care, mental healthcare, and substance abuse treatment. What started out as a good idea has evolved into a system where inefficiencies and abuses have corrupted 340B’s intent and harmed some patients. As a result, on a federal and state level, numerous pieces of 340B reform legislation have been introduced to stop abuses, protect patients, and overall ensure the program operates as intended.

One issue is the sheer number of covered entities taking advantage of the 340B discount pricing.[2] At the program's advent, safety-net hospitals, outpatient clinics, and community health centers were the first entities allowed to participate. Later, Congress expanded eligibility to add children’s hospitals, outpatient cancer center hospitals, rural referral centers, sole community hospitals, and critical access hospitals. Covered entities are supposed to serve large numbers of vulnerable community members by providing charity care and passing on savings. However, the lack of robust oversight and ambiguity in the 340B legislative language has allowed some entities to take advantage of the program. Some entities abuse the program by using the savings for profit instead of passing them on directly to patients or using them for services to serve them. Some entities participate in the program when they should not be qualified. Some larger hospitals do this by manipulating their business structures by acquiring smaller entities that qualify in the true spirit of the program.

Another significant issue is bad faith actions from some covered entities who are using 340B rebates to fund exuberant executive compensation, which is entirely made more egregious by the hospital systems simultaneously cutting their charity care for indigent patients.[3]

A notable piece of legislation recently introduced in Congress to affect 340B reform is a discussion draft bill entitled the ‘SUSTAIN 340B Act’ - which stands for ‘Supporting Underserved and Strengthening Transparency, Accountability, and Integrity Now’.[4] It was introduced by U.S. Senators John Thune (R-S.D.), Debbie Stabenow (D-Mich.), Shelley Moore Capito (R-W.Va.), Tammy Baldwin (D-Wis.), Jerry Moran (R-Kan.), and Ben Cardin (D-Md.), all members of the Senate 340B bipartisan working group. This bill is a comprehensive attempt at reform targeting many of the current weaknesses of the 340B program. It addresses multiple areas, such as transparency, contract pharmacy operations, program integrity, and accountability. 

Sen. John Thune | Photo Source: TIME

In one vein of accountability, this bill amends the current 340B legislation by defining parameters for what can be considered ‘child sites’.[4] Many covered entities operate more than one physical location. An example is a non-profit hospital that may have multiple clinics or service centers outside the main hospital where all entities are partaking of the 340B discount. This bill explicitly defines the operating relationships required to be considered a qualifying child site. This is necessary because many entities are improperly spreading their 340B privilege across outlets under their umbrella. 

Another accountability measure defined by the SUSTAIN 340B Act relates to reporting. Concerning patient and community benefits, the bill requires covered entities to show their proverbial ‘receipts’ and thus bringing some much-needed transparency to the program. The legislative verbiage mandates the reporting include data such as the financial demographics of covered entities served populations, specifics on how the 340B prescriptions utilized by patients improved their health, explanations of policies covered entities use to promote access and adherence to prescribed medication, and even detailed reporting of how the discounts received from the program are used.[4]

The legislation, in part, reads: “We believe that requiring covered entities to report detailed information regarding their program savings, policies, patient and prescription information, and then enabling that information to be publicly available by the Secretary will help ensure all stakeholders have trust and confidence that the program is being used as intended.”[4]

A more contentious part of the bill targets drug manufacturers. The bill specifically defines things that drug manufacturers cannot do. An example is where it explicitly states a drug manufacturer cannot impose a restriction on a covered entity as a condition to receive a discount, such as “…requiring the submission of claims data directly to the manufacturer out of submissions to the entity receiving the contract to maintain the clearinghouse under section 1150D of the Social Security Act.”[4] Most importantly, the bill defines prohibited activity, legal remedies, and monetary penalties that can be assessed if drug manufacturers break the rules.

The SUSTAIN Act also aims to enhance program integrity by implementing stronger guidelines for government audits of covered entities, preventing duplicate discounts by bad actors gaming the system between the 340B program and Medicaid, and reigning in health plans and pharmacy benefit managers attempts to restrict access to drugs in the 340B program.[4]

Dusty Garner, a long-time survivor of HIV and member of the ADAP Advocacy 340B Patient Advisory Group, passionately summarized: "Listen, it is about damn time Congress opened the books on this $54 Billion program and asked the corporate healthcare providers who are benefiting the most from it to do the same with their ledgers. Too many patients are drowning in medical debt, yet they're residing in areas with so-called nonprofit hospitals supposedly best suited for expanded access under the 340B Program. Where is all of this money going, cause we know too much of these 340B rebates aren't helping the patients who most need it."

Photo Source: CANN

Another less notable piece of legislation introduced was the ‘340B Pharmaceutical Access To Invest in Essential, Needed Treatments & Support Act of 2024’, known as the 340B PATIENTS Act.[5] It was introduced by Rep. Doris Matsui (D-Calif.), a known drug industry antagonist and a favorite of the American Hospital Association. Despite the legislation's short title, it appears to be more concerned with providers than patients. The 340B PATIENTS Act is not as comprehensive as the SUSTAIN Act. Its specific focus is to make amendments concerning contract pharmacy dealings and drug manufacturer enhanced reporting requirements. One section of the bill adds amended language to clarify that drug manufacturers are required to “offer 340B pricing for drugs purchased by a covered entity regardless of the manner or location in which the drug is dispensed, and section 340B prohibits drug manufacturers from placing conditions on the ability of covered entities to purchase and use 340B drugs, regardless of the manner or location in which they are dispensed.”[5]

Thomas Johnson, Executive Director of ASAP 340B, expressed sentiments concerning the 340B PATIENTS Act. He states, "While we welcome efforts to address 340B contract pharmacy arrangements, the 340B program needs comprehensive reforms that will restore its integrity and accountability and, most importantly, ensure underserved communities are benefiting. ASAP 340B was formed because nearly all stakeholders involved in the 340B program have grave concerns about its ability to serve the nation's safety net as was originally intended 30 years ago. Community Health Centers, patient, provider and consumer advocates, and leaders from the biopharmaceutical industry are at the table together, working with Congress on solutions that will go further to address the flaws in the 340B program currently putting America's safety net at risk."

Photo Source: ASAP 340B

The 340B program is a lifeline for covered entities and the communities they serve. Fighting to legislate its survival is imperative to improve the health and lives of those truly in need of its benefits. In a joint statement to the U.S. Senate Bipartisan 340B Working Group in response to a Request for Information, ADAP Advocacy and Community Access National Network perfectly described the dire need for reform. They explain: “When originally drafted, Congress did not include extensive parameters to govern the entities. This means that the statute is silent on many critical program requirements that are necessary for it to function correctly today, ensuring that patients, and not hospital networks, are seeing the benefit of discounted medicines. But it is now more than 20+ years later, and difficult to argue about what occurred then as compared to now. The challenge and the opportunity are to focus on what Congress wants the program to be today, who it should serve, what healthcare providers should be qualified as “covered entities,” etc.[6]

The current toxic political environment on Capitol Hill, which is exacerbated by the continued dysfunction in the House of Representatives, makes it highly unlikely anything gets done in Congress other than funding the government. But the introduction of 340B-specific legislation does demonstrate that the growing calls for reform of the 340B Program are finally being heard. The simple truth of the matter is the more patients learn about how the 340B Program could be better serving them rather than lining the pockets of corporate healthcare providers, they’re left asking: “340B: What about me?” Congress appears to be listening.

[1] HRSA. Sec. 340B Public Health Service Act. Retrieved from https://www.hrsa.gov/sites/default/files/hrsa/rural-health/phs-act-section-340b.pdf

[2] The Commonwealth Fund. (2022, September 8). The Federal 340B Drug Pricing Program: What It is, and why it’s facing legal challenges. Retrieved from https://www.commonwealthfund.org/publications/explainer/2022/sep/federal-340b-drug-pricing-program-what-it-is-why-its-facing-legal-challenges#:~:text=In%202015%2C%20the%20U.S.%20Government,left%20largely%20to%20police%20themselves.

[3] Hopkins, Marcus J.. (2023, November 2). 340B Covered Entities’ Revenue Witnessed Huge Executive Compensation Increases, Alarming Charity Care Decreases. The ADAP Blog Retrieved from https://adapadvocacyassociation.blogspot.com/2023/11/340b-covered-entities-revenue-witnessed.html 

[4].Thune, J., Stabenow, D., Moore, S., Baldwin, T., Moran, J., Cardin, B. (2024). SUSTAIN Act. Retrieved from https://www.thune.senate.gov/public/_cache/files/c3a678e3-12a5-4175-8a80-9246b76576ec/75E01A8968B679E3525395E2BB0CE7DB.ss340b-act-discussion-draft-.pdf

[5] Matsui, D. (2024, March 12). 340B PATIENTS Act. Retrieved from https://matsui.house.gov/sites/evo-subsites/matsui.house.gov/files/evo-media-document/MATSUI_022_xml_final.pdf

[6] ADAP Advocacy, Community Access National Network. (2023, July 23). Joint Statement. Retrieved from https://www.adapadvocacy.org/pdf-docs/2023_ADAP_CANN_Public_Comment_Senate_RFI_340B_07-24-23.pdf

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. 

Understanding Atlanta’s Persistently High Rate of HIV

By: Ranier Simons, ADAP Blog Guest Contributor

Since the 1950s, Atlanta is commonly known as “Hot Lanta” popularized by the Allman Brothers Band’s song because of its hot and humid climate.[1] But the weather isn't the only thing "hot" in Atlanta as the metro area surrounding the city has become a burning epicenter of new diagnosis for HIV.

Photo Source: ANIZ

Proper data collection and analysis take time. This is especially true regarding public health surveillance and research. It is better to have robust sourcing of quality data collection than analysis of rushed volumes of collected data.[2] The Centers for Disease Control & Prevention (CDC) recently released a national HIV data analysis of infection rates from 2021. Overall, the national rate of new HIV infections has been decreasing over the past few years. However, this is not entirely true for the South.[3] Reporting indicates problematic infection trends in several southern metropolitan areas, one such area being metro Atlanta. 

Data shows that in 2021, metro Atlanta had the third highest new HIV infection diagnosis rate of metropolitan areas, only bested by Miami, Florida, and Memphis, Tennessee.[3] This data gives added context to preliminary data observed presently in 2024. According to Dwayne Ford, director of HIV prevention services with AIDS Atlanta, there are more reported positive individuals living with HIV in the first quarter of 2024 than in the first quarter of 2023.[4]

Various treatment and prevention tools exist, so healthcare professionals and community groups are trying to identify where more work needs to be done to reverse Atlanta and Georgia’s new infection rates. While metro Atlanta is the third highest ranking in new infections for metropolitan areas, Georgia is fourth overall as a state. One challenging area of concern is funding. Georgia is one of the few states that have not expanded Medicaid. If Georgia fully expanded Medicaid as allowed under the Affordable Care Act, over half a million Georgia residents would become eligible for health insurance.[5] 

Photo Source: Atlanta Journal Constitution

This would enable over half of the Georgian residents who are uninsured and enrolled in the Ryan White program to be moved to Medicaid. They would still be able to get all the care they received under Ryan White in addition to other services not available through Ryan White. That, in turn, would free up approximately $53.7 million of Ryan White funding to help non-Medicaid eligible people living with HIV not presently accessing services.[4] Treatment is prevention since increasing the number of people on ART means increasing viral suppression, lowering the number of those able to transmit HIV. Moreover, expanding Medicaid would mean increasing access to PrEP since Ryan White Funding cannot be used for PrEP medications nor its associated medical visits and laboratory testing.[6] African American and Hispanic males comprised the majority of reported new HIV infections yet have much lower utilization of PrEP in comparison to white residents.[3]

Access is a significant issue for low-income residents and the African American and Hispanic populations, which are disproportionately represented in new infection numbers. However, stigma is also still an issue.[3] In African American and Hispanic communities, HIV stigma remains a barrier to care, testing, and support. Efforts to encourage and expand testing lose impact when those who discover their positive status do not seek treatment. It is vital to bolster efforts to get newly diagnosed individuals into treatment as soon as possible and to help them remain in treatment. Support is needed since fear and privacy concerns hinder vulnerable populations from wanting their medications discovered by friends and family. Additionally, fear of the stigma of being seen at public clinics or other healthcare facilities hinders proper follow-up care and testing.

Support and prevention are the two areas many concerned parties are focusing on. Expanding prevention efforts such as PrEP access, education, and culturally competent messaging are imperative. Improving upon existing measures to help those negatively affected by social determinants of health, such as lack of transportation and insurance, is also necessary. 

Photo Source: endhivatl.org

The Fulton County Department for HIV Elimination recently launched a new website, ENDHIVATL.ORG,  in response to the metropolitan Atlanta area epidemic. Citizens can use the site to find service providers based on the services they provide and their proximity to where they live. The site also provides up-to-date information concerning how and where to access PrEP and other medical and non-medical services. To help address stigma, the site has a prominently displayed section entitled ‘Positive & Proud.’ It contains personal stories of local community members living with HIV regarding their lives in general and their experiences with utilizing the Department for HIV Elimination services. There is even a section of the site dedicated to assisting healthcare providers.

Atlanta’s high rate of HIV infection has persisted for years. While rates have declined slightly, they are still disproportionately higher than the rest of the country. Hopefully, continued efforts to highlight the status quo, maintain awareness, and provide further support and prevention will soon result in improved lives and outcomes.

[1] Kane, Deborah (2024, April 10). What is the nickname of Atlanta Georgia? NCESC. Retrieved from https://www.ncesc.com/geographic-faq/what-is-the-nickname-of-atlanta-georgia/

[2] Chiolero, A., Tancredi, S., & Ioannidis, J. P. A. (2023). Slow data public health. European journal of epidemiology, 38(12), 1219–1225. https://doi.org/10.1007/s10654-023-01049-6

[3] Gaines, J. (2024, April 1). New HIV case rate in metro Atlanta third highest in nation. Retrieved from https://www.ajc.com/news/atlanta-news/new-hiv-case-rate-in-metro-atlanta-third-highest-in-nation/6TDMS6CUTZG7RPVPRLE6O3JZCY/

[4] 11Alive. (2024, April 4).HIV cases on the rise in metro Atlanta - What local clinic says about it. [Video]. YouTube. https://www.youtube.com/watch?v=h2jh2TgxfcQ&list=WL&index=1

[5] Equality Foundation of Georgia. (2022). Implications of Medicaid expansion on Georgia's HIV Budget. Retrieved from https://georgiaequality.org/wp-content/uploads/2022/01/REPORT-Medicaid-Expansion-and-Ryan-White.pdf?emci=61ee3ed9-f179-ec11-94f6-c896650d4442&emdi=ea000000-0000-0000-0000-000000000001&ceid=

[6] Department of Health and Human Services. (2021, November 16). HRSA Letter to Ryan White Program Colleagues. Retrieved from https://ryanwhite.hrsa.gov/sites/default/files/ryanwhite/hiv-care/prep-dcl-november-2021-508.pdf

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's up with CRISPR Therapy's Impact on HIV Replication and the Potential for a Cure?

By: Ranier Simons, ADAP Blog Guest Contributor

Scientific innovation in the fight against HIV created the current landscape of antiviral treatment, which allows people living with HIV (PLWH) to manage chronic viral infection and lead long, healthy lives. Recent medical advancements give a glimmer of hope for advanced viral suppression and the potential for a future cure. A recent University of Amsterdam laboratory study using CRISPR-Cas9 gene editing technology was able to eliminate HIV from infected cells in a controlled environment outside of the body.[1,2] This development is proof of concept, which could mean eradicating HIV from the bodies of PLWH will be achievable one day.

Photo Source: YouTube | SciTech Alerts

CRISPR stands for ‘clustered regularly interspaced short palindromic repeats.’[3] It is technology based on how bacteria naturally use gene editing systems to protect themselves from viral infection. CRISPR-Cas is a system. Cas is an enzyme, and Cas9 is an enzyme that specifically can cleave DNA. CRISPR is a sequence of RNA. In simple terms, the CRISPR-Cas9 complex is effectively a ‘seek and destroy’ pair of molecular scissors that can search for and cut out undesirable genetic material.[4]

When the HIV invades the body and infects cells, it integrates its genetic material into the host cell’s genome. Current antiviral medications help to prevent the virus from replicating in the body. However, ART does not attack the dormant virus that lies in wait in viral reservoirs. This is why lifelong ART is necessary since HIV infection can rebound from these reservoirs if medication is discontinued. Dr. Elena Herrera-Carrillo and her team at the University of Amsterdam recently used CRISPR-Cas9 technology to completely eliminate the HIV virus from cell cultures.[5]

The team focused on a specific part of the HIV viral genome that seems to be present in all known HIV strains. Testing with infected CD4+ T-cells, the team modified their CRISPR-Cas9 complex to inactivate and excise the targeted HIV viral DNA. Thus, HIV was eliminated entirely from the cells since the genetic code necessary to form it was removed, effectively destroying HIV’s building blueprint. Additionally, they were able to target what they described as hidden reservoir cells by identifying specific proteins present on their cell surfaces.[5]

Photo Source: Newsmax

This study is promising, but by no means is an immediate cure for HIV. The experiment was a very specified cell culture exercise outside of the body. HIV can infect many kinds of cells and tissues of the body with varying characteristics and environments. Future research needs to investigate how to target HIV in all those circumstances and conditions.[5] Also, HIV reservoirs have long half-lives and can be found in many different cells and tissues, such as the central nervous system and the male urogenital tract.[6] To effectively eradicate HIV from the body would require eliminating HIV from every infected cell and every latent reservoir. No proverbial stone could be left unturned since even the smallest one percent of a reservoir could potentially reactivate and spawn HIV replication.

Gene editing can also have unintended consequences.[7] When genes are cut with CRISPR technology, the process by which cells heal the excisions and reform introduces errors into the genome. Without precise targeted CRISPR techniques, gene sequences can be edited and rewritten in ways that cause mutations, resulting in cancer promotion or other unwanted biological process alterations. The human body is a very complex system of systems. Developing a CRISPR cure for HIV would require foolproof ways to enter appropriate cells while avoiding others, in addition to ways to mitigate dangerous side effects.

While a CRISPR cure for HIV is nowhere near to becoming a reality, the Amsterdam study is a source of hope and a guide for the future. Innovation is incremental. This study will be a steppingstone and guidepost for other scientists to build upon and spawn future breakthroughs. Dr Carrillo states, “We hope to achieve the right balance between efficacy and safety of this CURE strategy…Our aim is to develop a robust and safe combinatorial CRISPR-Cas regimen, striving for an inclusive ‘HIV cure for all’ that can inactivate diverse HIV strains across various cellular contexts.”[1] While we will not see human clinical trials until the science reaches this point, at least we have a newly developing tool to add to the HIV antiretroviral arsenal.

[1] Good News Network. (2024, March 23). Scientists discover potential HIV cure that eliminates disease from cells using CRISPR-Cas gene editing. Retrieved from https://www.goodnewsnetwork.org/scientists-discover-potential-hiv-cure-that-eliminates-disease-from-cells-using-crispr-cas-gene-editing/

[2] Wilson, C. (2024, March 19). CRISPR could disable and cure HIV, suggests promising lab experiment. Retrieved from https://www.msn.com/en-us/health/other/crispr-could-disable-and-cure-hiv-suggests-promising-lab-experiment/ar-BB1kbDkU

[3] National Institutes of Health. (2024, March 27). CRISPR. Retrieved from https://www.genome.gov/genetics-glossary/CRISPR#:~:text=CRISPR%20(short%20for%20%E2%80%9Cclustered%20regularly,editing%20systems%20found%20in%20bacteria.

[4] Hussein, M., Molina, M. A., Berkhout, B., & Herrera-Carrillo, E. (2023). A CRISPR-Cas Cure for HIV/AIDS. International journal of molecular sciences, 24(2), 1563. https://doi.org/10.3390/ijms24021563

[5] American Association for the Advancement of Science. (2024, March 19). HIV in cell culture can be completely eliminated using CRISPR-Cas gene editing technology, increasing hopes of cure. Retrieved from https://www.eurekalert.org/news-releases/1038161

[6] Pierson, T., McArthur, J., & Siliciano, R. F. (2000). Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annual review of immunology, 18, 665–708. https://doi.org/10.1146/annurev.immunol.18.1.665

[7] Hunt, J. M. T., Samson, C. A., Rand, A. D., & Sheppard, H. M. (2023). Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells. Human genetics, 142(6), 705–720. https://doi.org/10.1007/s00439-023-02561-1

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.