Towards an HIV Cure: Benefits and Risks of a CRISPR Intervention

The HIV/AIDS epidemic started with its first case in 1981 and has caused irreparable, ongoing damage to communities around the world. Scientists around the globe have quickly moved to develop treatments and cures for those who contract HIV/AIDS. In many parts of the world, people have access to treatment that will stop a decline in quality of life for those living with the disease. These treatments are called antiretroviral therapies and work to reduce the HIV viral load in a patient who is taking the drug [1]. Decreasing the viral load allows the body to recover and fight off HIV infection and related illnesses and certain HIV-related cancers. These drugs often reduce the possibility of transmission of HIV as well. Overall, these therapies provide those living with HIV a chance at maintaining a high quality of life and increased life expectancy compared to those who are not being treated with HIV [2].

However, these treatments are not available everywhere. Antiretroviral therapies and pre-exposure prophylaxis (PrEP) are widely available in the United States for those who can afford them. Pre-exposure prophylaxis is a medication that is highly effective at reducing the chances of contracting HIV from sexual contact or drug use [3]. It is commonly prescribed for those at risk of contracting HIV. The gap between those who can access these treatments and those who cannot has a substantial impact on the prevalence of the disease. In South Africa, one country where the AIDS crisis is most severe, the HIV/AIDS epidemic is far from over. There, more than 18 percent of the adult population is infected with HIV/AIDS, whereas in the United States, the prevalence rate is below 1 percent [4]. These numbers are staggering. 

They illustrate that the United States is faring quite well with regard to the HIV/AIDS epidemic, while other countries are continuing to struggle. In South Africa, the rate of new infections has lowered over the past ten years, but the number of people living with HIV/AIDS is increasing faster than the rate at which access to treatment can match [4]. Additionally, antiretroviral therapies require that you take them every single day. This has a possibility of being logistically challenging when medication starts to dwindle among a population. If you stop taking the antiretroviral therapy, the virus will begin to remultiply and you will become transmissible again [5]. It may be easy to take medication once a day if you have access to a stable source of medication, but this is not everyone’s reality. Luckily, cures have been undergoing development for some time.

One treatment that is showing promise is being developed using a cutting edge gene editing tool CRISPR. CRISPR may be able to act as a functional cure for HIV by inactivating integrated HIV DNA [6]. While CRISPR is a promising genetic tool, it is still in its early stages of being researched and applied. It requires further research and development in order to be both safe and effective. However, if safe and effective, it would allow for people who contract HIV to be able to take this treatment and be cured of HIV in a way that antiretroviral therapies would not be able to match. Tackling the HIV/AIDS epidemic would be much more logistically plausible and would not require broad, long-term medication regimes that could be hard, or, for some, impossible to follow [7]. 

The development of an HIV cure using CRISPR, however, is complicated and there are current limitations on the use of CRISPR as a way to neutralize or eradicate HIV in a host. One limitation is the delivery of the CRISPR/Cas apparatus when in vivo [8]. In some tests on mice and nonhuman primates, there has been successful obliteration of the HIV virus. However, precise targeting remains a significant challenge for effective administration of a CRISPR HIV cure. Clinical trials involving cell and gene therapy (CGT) have left people who participated in the trials with Leukemia, other illnesses, and even organ failure, which ultimately led to death [9]. These examples illustrate the very dangerous nature of using CRISPR to treat illnesses without extensive testing. And, even with further testing and development, it may be extremely difficult to predict the effect CRISPR and CGT will have on people. However, if the kinks are worked out, using CRISPR and other CGTs can have an enormous impact on not only HIV treatment, but also HIV prevention [8]. 

Every year, hundreds of thousands of people succumb to HIV/AIDS, with roughly two thousand people dying from the illness every day [9]. A cure is desperately needed. If we press forward with clinical trials using CRISPR or other forms of gene therapy, the risk associated with them may be too great. However, there is only so much that global access to antiretroviral therapies and PrEP can do for those who are living with – or are at higher risk of contracting – HIV. These are questions facing bioethicists and clinicians around the world and, frankly, an HIV cure could not come any sooner.

Work Cited:

1. U.S. Department of Health and Human Services. (2021). HIV treatment: The basics. National Institutes of Health. Retrieved April 7, 2023, from https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics. 

2. Centers for Disease Control and Prevention. (2022). Treatment. HIV. Retrieved April 23, 2023, from https://www.cdc.gov/hiv/basics/livingwithhiv/treatment.html 

3. Centers for Disease Control and Prevention. (2022). About PrEP. HIV. Retrieved April 23, 2023, from https://www.cdc.gov/hiv/basics/prep/about-prep.html. 

4. South Africa. UNAIDS. (2022, December 4). Retrieved April 8, 2023, from https://www.unaids.org/en/regionscountries/countries/southafrica. 

5. Wilberg, M. (2020, October 1). My HIV is undetectable, can I stop my medication? NAMaidsmap. Retrieved April 23, 2023, from https://www.aidsmap.com/about-hiv/faq/my-hiv-undetectable-can-i-stop-my-medication. 

6. 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. 

7. Dybul, M., Attoye, T., Baptiste, S., Cherutich, P., Dabis, F., Deeks, S. G., Dieffenbach, C., Doehle, B., Goodenow, M. M.. Jiang, A., Kemps, D., Lewin, S. R., Lumpkin, M. M., Mathae, L., McCune, J. M., Ndung’u, T., Nsubuga, M., Peay, H. L., Pottage, J., … Sikazwe, I. (2020). The case for an HIV cure and how to get there. Lancet HIV, 8: e51-58. https://doi.org/10.1016/ S2352-3018(20)30232-0.

8. Bhowmik, R., Chaubey, B. (2022). CRISPR/Cas9: a tool to eradicate HIV-1.. AIDS Res Ther 19, 58 . https://doi.org/10.1186/s12981-022-00483-y. 

9. World Health Organization. (n.d.). HIV, number of people dying from HIV-related causes. World Health Organization. Retrieved April 8, 2023, from https://www.who.int/data/gho/data/indicators/indicator-details/GHO/number-of-deaths-due-to-hiv-aids. 

The Indian Health Service and Turning a Blind Eye

The Indian Health Service (IHS)  was founded on July 1st, 1955 and its mission is to serve the population of indigenous peoples who are members of federally recognized tribes in the United States [1]. IHS has hospitals across the country that serve the millions of people who belong to federally-recognized tribes. However, the IHS has been severely underfunded for much of its existence and has time and time again failed to provide high quality, reliable service to the indigenous population of the United States. With these observations in mind, I argue that the United States commits something larger than simply a broken promise by neglecting their relationship to tribal nations, but rather commits egregious bioethical violations. 

The obligation for the federal government to provide health services to indigenous peoples is part of the larger doctrine of trust, which was established in a series of court cases and treaties, as well as in Article 1 Section 8 of the United States Constitution, which grants the United States federal government jurisdiction over the commerce and treaties of tribal nations [2]. Within this jurisdictional declaration, tribal nations become a pseudo-subsidiary if you will of the United States, needing to conform to federal law, but still able to in-part retain their sovereignty. With the formation of this relationship, federal systems dedicated to the health and wellbeing of indigenous peoples took shape. This doctrine of trust has only been applicable to the Tribal Nations that are federally recognized and does not encompass all indigenous peoples who live within the border of the United States. This differentiation is important because during the era of termination, a period of time between 1953 and 1969, many tribal nations lost their status as federally recognized tribes, thus relieving the federal government of their obligation to recognize their sovereignty [3]. One example, of many, the Klamath people of Oregon, had their land distributed and lost their status as a federally recognized tribe, which meant the dissolution of the government of the Klamath peoples and the loss of their privileged relationship with the federal government [3]. Even those who are recognized by the federal government are not afforded the same access to health services that other citizens of the United States receive. 

The IHS and the funding for healthcare for the rest of the citizens of the United States is fundamentally different. The IHS receives the majority of its funding designated under the category of “discretionary spending” in the federal budget unlike medicare, another federally-funded health plan, which is categorized as mandatory spending [4]. This categorization opens the door for lack-luster appropriations being allocated to the Indian Health Service. The documentary Don’t Get Sick After June describes this very problem. The funding for the IHS begins on the first day of the fiscal year, the first day of October, however due to the inadequacy of funding that the IHS is given, it is financially unable to provide adequate funds to health care institutions on tribal land throughout the entire fiscal year, particularly as funding for the IHS predictably runs out in June year after year [5]. The IHS on average only has 59 percent of its annual appropriations met and in 2013, IHS per capita spending for individuals was $2,849 compared to $7,717 nationally [6]. 

In addition to the inadequacy of the funding for the IHS, the impacts of settler colonialism continue to have profound health impacts on indigenous peoples. Colonialism not only devastated and displaced indigenous communities, but broke down systems of community health such as access to traditional food sources, clean water, and land [7]. These systems of community based care dependent on the lands in which indigenous peoples were living, and the traditional practices that were tied to these lands, were replaced with systems such as the IHS. Some of the ways these impacts manifest themselves is the presence of higher mortality rates for alcoholism, which is over five times that of the national average, diabetes, which is almost double the mortality rate of the average population, cervical cancer, and maternal deaths [6]. Food insecurity also plays a large role in the disproportionate prevalence of disease and illness such as diabetes. In fact, over a quarter of the indigenous population experiences food insecurity and food deserts are common on reservations [8]. These food deserts leave people to turn to unhealthy options simply out of necessity, which in combination with the inadequate funding of the IHS, leaves people living in these areas unable to improve their health conditions. 

Clearly, discrepancies are nested in the underfunding and inadequacy of the IHS, but they are also nested within the structures and conditions within which indigenous peoples currently live. While it seems to have been easy for the United States to turn a blind eye from the needs of the indigenous peoples who live within its borders, it is clear that with regard to the health of these populations, it is carrying out gross bioethical wrongs. One of the principles of bioethics is justice, which is based upon the equal distribution of care to all groups in a society, and that a caretaker must respect and act in accordance with rights and obligations [9]. Another aspect of the justice principle of bioethics is that rights and obligations must be met, which in this case includes following through with stipulations from centuries ago that formed the basis of the “doctrine of trust.”

It would take immense structural change to correct for the health discrepancies in indigenous communities – much more than simply increasing funding for the IHS, but it may be a good place to start. Increasing funding would allow for more consistent care to be provided to these communities and could help to slow the rate at which native peoples are succumbing to disease and illness. Providing more access to food would be another way in which the health of this group of people could be improved. Broad, comprehensive investments into the health and wellbeing of these communities could go a long way, and would be a small step in the right direction on the way to correcting the federal government’s ethical wrongs. 

References

1. "If you knew the conditions..." Health Care to Native Americans: Indian Health Service Today. (2010, November 23). U.S. National Library of Medicine. https://www.nlm.nih.gov/exhibition/if_you_knew/ifyouknew_09.html#:~:text=The%20Indian%20Health%20Service%20. 

2. Basis for Health Services. Indian Health Service. (n.d.). U.S. Department of Health and Human Services. https://www.ihs.gov/newsroom/factsheets/basisforhealthservices/. 

3. 1953 to 1969: Policy of Termination and Relocation (n.d.). Stanford Medicine. https://geriatrics.stanford.edu/ethnomed/american_indian/learning_activities/learning_1/termination_relocation.html. 

4. Heisler, E. J. (2022) Indian Health Service (IHS) FY2022 Budget Request and Funding History: In Brief (CRS Report No. R47004). https://crsreports.congress.gov/product/pdf/R/R47004#:~:text=117%2D58.

5. Ritchie, C. (Director). (2010). Don’t Get Sick After June: American Indian Healthcare [Film]. Rich-Heape Films, Inc. 

6. National Congress of American Indians. (2016). Health Care: Reducing Disparities in the Federal Health Care Budget. https://www.ncai.org/policy-issues/tribal-governance/budget-and-approprations/07_FY2016_Health_NCAI_Budget.pdf. 

7. Jensen, A., & Lopez-Carmen, V. A. (2022) The “Elephants in the Room” in U.S. global health: Indigenous nations and white settler colonialism. PLOS Global Public Health. https://doi.org/10.1371/journal.pgph.0000719.

8. How Hunger Affects Native American Communities. (n.d.). Move for Hunger. https://moveforhunger.org/native-americans-food-insecure#:~:text=Overall%2C%20over%20a%20quarter%20of,of%20access%20to%20quality%20healthcare. 

9. What are the Basic Principles of Medical Ethics?. (n.d.). https://web.stanford.edu/class/siw198q/websites/reprotech/New%20Ways%20of%20Making%20Babies/EthicVoc.htm#:~:text=Bioethicists%20often%20refer%20to%20the,beneficence%2C%20and%20non%2Dmaleficence. 

Painful Justice: Botched Executions and Capital Punishment

The death penalty has been practiced as a fundamental tool in criminal and judicial systems for thousands of years and has played an integral role, both socially and punitively, in many ancient and modern societies. The practice of capital punishment in the United States began in the colony of Jamestown with the first reported execution occurring in 1608 [1]. This practice has withstood the test of time, remaining a possible sentence in twenty four states [2]. Many states, most recently, Virginia, which outlawed the practice of the death penalty in 2021, have stopped carrying out executions altogether as a form of criminal punishment. Currently in the states where the death penalty is still practiced, the most common and widely used method of execution is lethal injection, in which various medications are administered through intravenous injections resulting in the death of the prisoner. This method of execution is regarded, generally, as the most humane and is not meant to cause any pain to the person being executed [3]. 

In striving for this aversion to pain in the practice of lethal injection, legislators and advocates aim to parallel the philosophies of the medical field. In medicine, practitioners attempt to reduce the pain of patients undergoing procedures through anesthesia and control for pain in post-op recovery with pain medications as strong as morphine or fentanyl. When all goes well, lethal injection is similar to any other medical procedure where pain is managed or even completely absent for the patient. However, this is not always reality. Lethal injection has the highest rate of failure among other contemporary methods of execution sitting at 7.12%, while other methods such as electric chair or firing squad have failure rates of 1.92% and 0% respectively [4]. 

These so-called botched executions subject the person being executed to visible extreme pain, discomfort, and distress. One such execution made national news when an Oklahoma man was seen convulsing and throwing up during his execution [5]. In multiple cases, executions have failed due to prisoners who have compromised veins as a result of drug use that make it harder to insert an IV through which to inject the drugs. In these circumstances, a decision must be made to continue with the execution by finding other ways to insert IVs, such as in hands, necks, and other places on the body, causing extreme discomfort for the prisoner involved [4]. In these cases, physicians often aid technicians in establishing an IV through which to administer the drugs. And in this way, physicians play a central role in the medical killing of another human being. If the consistency of lethal injection as a mode of capital punishment requires physicians to play a role in carrying out this work, physicians must face various ethical dilemmas in weighing the benefits of both “justice” and medical ethics, similar to the ethical dilemmas of euthanasia or assisted suicide. 

 Lethal injection, the most “humane” method of execution, comes with complications not seen with other methods of executions that put into question the efficacy of lethal injection. The use of firing squads has dwindled over the years due to the sheer carnage it endows the body of the prisoner with, and execution by electric chair has similarly dwindled due to concerns over  pain and suffering during the procedure [6]. So now, we have been left with lethal injection. If the most “humane” method of execution is still having unforeseen consequences for the prisoners who are being executed, perhaps capital punishment as a whole needs to be reevaluated as a practice. 

References 

1.  “History of the Death Penalty.” Death Penalty Information Center. https://deathpenaltyinfo.org/facts-and-research/history-of-the-death-penalty/early-history-of-the-death-penalty. 

2.  “State by State,” Death Penalty Information Center. https://deathpenaltyinfo.org/state-and-federal-info/state-by-state. 

3.  “So Long as They Die: Lethal Injection in the United States,” Human Rights Watch. https://www.hrw.org/report/2006/04/23/so-long-they-die/lethal-injections-united-states#:~:text=Compared%20to%20electrocution%2C%20lethal%20gas,it%20mimics%20a%20medical%20procedure. 

4.  “Botched Executions,” Death Penalty Information Center. https://deathpenaltyinfo.org/executions/botched-executions. 

5.  “Oklahoma executes inmate who dies vomiting and convulsing,” AP, October 28, 2021. https://apnews.com/article/us-supreme-court-prisons-executions-oklahoma-oklahoma-attorney-generals-office-6e5eedd1956a38f83db96187651f145c. 

6. “South Carolina judge halts the use of firing squad, electric chair,” Washington Post, September 7, 2022. https://www.washingtonpost.com/nation/2022/09/07/south-carolina-firing-squad-electric-chair/.