Understanding Why HIV-Positive Individuals Would, or Would Not, Risk Their Lives for a Cure
Maggie L. Shaw
The investigators of the HIV Cure Research study, the results of which appeared recently in New in Ethics & Human Research
, wanted to better understand and show why HIV-positive individuals on antiretroviral therapy would willingly risk their lives to find a cure for HIV and AIDS.1
To help understand the seriousness of the choices HIV-positive individuals make to risk their lives—that is, the risk-benefit ratio and what they value in the search for a cure—it is impotant to appreciate some history on the fight to end HIV and AIDS.
Reports of the first cases of AIDS, back when it was termed “gay-related immune deficiency,” came from the CDC in 1981.2
And the first clinical trial of an antiretroviral drug to treat HIV and AIDS took place in 1986, with the investigation of zidovudine, also known as azidothymidine (AZT).3
Despite life-threatening adverse effects (AEs) that include hypersensitivity, lactic acidosis, severe anemia, neutropenia, liver problems, and myopathy,4
the drug was approved by the FDA on March 19, 1987,5
after only 20 months of testing.6
Originally a failed cancer drug from Burroughs Wellcome (BW), the company jumped into the fray of testing potential HIV agents in the early years of the epidemic when it brought AZT back from the dead, somewhat refurbished and renamed Compound S. Following seemingly successful results with HIV-infected animal cells, BW sent samples of AZT for additional testing to the FDA and National Cancer Institute.6
Clinical oncologist and the head of the agency at that time, Samuel Broder, MD, coined these early years “a time of chaos.”7
Using a blinded cohort of 300 individuals with confirmed cases of AIDS who were randomly assigned AZT or a sugar pill for 6 months, the trial that helped lead to AZT’s approval lasted a scant 16 weeks—having followed safety trials for AEs. Altogether, there were 20 deaths. BW justified the short time frame, reasoning “it wouldn’t be ethical to continue the trial and deprive one group of a potentially life-saving treatment.” At this time, the FDA’s drug approval process took 8 to 10 years. But with the urgency of the AIDS epidemic clear—reported cases jumped from 270 in 1981 to 3064 in 1983, an astounding 1035% in only 2 years8
—that timeline was accelerated to just 20 months for AZT, for a reduction in time to approval of almost 84%.6
To this day, the study remains controversial over arguments on AZT’s true effectiveness. Patients allegedly pooled pills to increase their odds of not getting the placebo, and there were no specific guidelines to follow to treat adverse comorbid conditions, like pneumonia, that AZT was not meant for. Also, the yearly cost at the time was $8000.6
All in all, the FDA was criticized for rushing the drug to market and BW for the price. However, with the epidemic raging on, the FDA was also criticized for not bringing additional drugs to market fast enough when AZT stopped working.6
Today, despite there being 55 individual and combination drugs available to treat HIV and AIDS,9
32 million people have died of HIV and 37.9 million were living with the disease at the end of 2018,10
with 1.1 million of those in the United States.11
However, there are also 12 clinical trials underway investigating various combination treatments, while a cure remains elusive.12
Which brings us back to the present study, in which the investigators interviewed 22 HIV-positive individuals to find out how much, if any, risk they were willing to accept if it meant finding a cure for their disease and preventing death in others—but maybe not themselves. There were 16 men and 6 women, with an average age of 49 years (range, 33-61); they had been HIV-positive for 6 months to 27 years; and their personal information was deidentified.1
The study authors found that almost 25% would voluntarily risk “near-certain death” (ie, 99%-100% chance of dying) if doing so could lead to a cure for the disease and that those who expressed this desire understood the risk they were willing to take. Their reasons fell into 6 categories1
- Altruism: “I would volunteer to be the one to die if 99 could be cured. It’s humanity. It’s human compassion.”
- Nothing to lose: “I got to be positive that I might die, and I would be—I’d be content with that.”
- Psychosocial benefits: “That would probably be the only reason I would want to take a cure, is to remove that element, to not feel in any way disadvantaged or stigmatized.”
- Avoid future health changes from continued HIV infection: “I think HIV is going to shorten my life.”
- Positive attitudes toward health care research: “I am 100% behind, you know, any type of research. If it doesn’t help me, it’ll help the younger generation and the people to come.”
- Multiple reasons for risk of death: “I am a strong person, and I am not going to live forever. It is about the next man, the next woman, and you have to have the mindset to care about people, which I do.”
For those not
willing to risk their lives, the investigators found that their reasons fell into 4 categories1
- Negative attitudes toward healthcare research: “I don’t do clinical trials…I am not a guinea pig.”
- Cure not worth it: “I have no risk of dying from the medication at this point, and I have no risk of getting reinfected.”
- General unwillingness to risk death: “A cure would be wonderful, but going through it…and then I might croak…I cannot risk that.”
- Uncertainty about risk taking: “I’d be scared. And most likely, I probably wouldn’t…Because I still [have] my life ahead of me.”
“We view the findings (and the point of this study) as providing a realistic flavor of the potential reasons
people living with HIV might have for being willing to assume risk (even quite high risk) for the sake of an HIV cure even when their disease is stable and well managed,” the authors stated. “There is a tendency to assume that people willing to take such risks don’t understand the nature, purpose, or outcome of HIV cure trials. Our study challenges this notion.”
For future studies, they suggest additional ethical safeguards that include a greater understanding of patient preferences for risk taking; extensive interview processes, with informed consent; asking if trials have social value, favorable risk-benefit balances, and scientific validity; and trial oversight that incorporates empirical data to help with trial design and consent.
1. Kratka A, Ubel PA, Scherr K, et al. HIV cure research: risks patients expressed willingness to accept. Ethics Hum Res.
2019;41(6):23-34. doi: 10.1002/eahr.500035.
2. History of AIDS. History channel/A&E Television Network website. history.com/topics/1980s/hisotry-of-aids. Published July 13, 2017. Updated May 6, 2019.
3. Bartlett JG. Ten years of HAART: foundation for the future. Medscape website. medscape.org/viewarticle/523119. Published 2006. Accessed December 18, 2019.
4. Zidovudine. AIDSinfo/National Institutes of Health website. aidsinfo.nih.gov/drugs/4/zidovudine/0/patient. Updated January 20, 2019. Accessed December 18, 2019.
5. HIV/AIDS historical time line 1981-1990. FDA website. www.fda.gov/patients/hiv-timeline-and-history-approvals/hivaids-historical-time-line-1981-1990#1988. Accessed December 18, 2019.
6. Park A. The story behind the first AIDS drug. Time.
March 19, 2017. time.com/4705809/first-aids-drug-azt/. Accessed December 18, 2019.
7. Broder S. The viral impact of HIV/AIDS. Presented at: TEDxGeorgiaTech; April 2019; Atlanta, GA. youtube.com/watch?v=LsDg_L-zJPM. Accessed December 20, 2019.
8. History of HIV and AIDS overview. Avert website. avert.org/professionals/history-hiv-aids/overview. Updated October 10, 2019. Accessed December 18, 2019.
9. FDA approval of HIV medicines. AIDSinfo website. aidsinfo.nih.gov/understanding-hiv-aids/infographics/25/fda-approval-of-hiv-medicines. Accessed December 20, 2019.
10. Global Health Observatory (GHO) data: HIV/AIDS. World Health Organization website. who.int/gho/hiv/en/. Accessed December 20, 2019.
11. US statistics: fast facts. HIV.gov website. hiv.gov/hiv-basics/overview/data-and-trends/statistics. Updated March 13, 2019. Accessed December 20, 2019.
12. Clinicaltrials.gov website. clinicaltrials.gov/ct2/results?cond=HIV+drug&Search=Apply&recrs=d&age_v=&gndr=&type=Intr&rslt=. Updated January 13, 2017. Accessed December 20, 2019.