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Karumah / COVID-19  / Overcome Vaccine Hesitancy Among PLWH by Acknowledging the History of AZT

Overcome Vaccine Hesitancy Among PLWH by Acknowledging the History of AZT

By Juan Michael Porter II
This post originally appeared on The Body:

While there is an ongoing debate over whether or not living with HIV constitutes increased risk for severe COVID-19 unto itself―particularly for people who are adherent to their antiretroviral regimen, have attained viral suppression, and have robust CD4 counts―on July 14, the World Health Organization (WHO) announced that it had determined that people living with HIV (PLWH) should receive COVID-19 vaccination prioritization.

The agency’s decision was based on a report using data from 15,522 cases of people who were hospitalized with COVID-19 infections and were living with HIV. This information was submitted to the WHO Global Clinical Platform for COVID-19 by 24 countries between January 1, 2020 and April 29, 2021.

It should be noted that 94.6% of cases included in this report were from South Africa alone; that “information on antiretroviral therapy was only available in 40% of the [submitted] cases”; and that relevant risk factors, such as body mass index, and results after hospital discharge were entirely absent from the analysis. Nevertheless, citing severe to critical reactions to COVID-19 in many of these individuals, WHO determined “HIV to be an independent risk factor for in-hospital mortality” in South Africa and, according to its limited data set provided from individuals living in the United States, that PLWH are “at increased risk for poor outcomes (mainly owing to higher rates of severe disease requiring hospitalization).”

Therapies With a Troubling Past

Despite the WHO’s determination, there is no existing data collected on how many PLWH have been vaccinated or if the HIV-positive community expresses the same level of skepticism about the vaccines as do sectors of the LGBTQ community. For instance, according to a survey involving 22,000 LGBTQ adults across the U.S. that was conducted by Human Rights Campaign (HRC) before vaccines were widely available, 29% of Black LGBTQ adults expressed that they were very likely to get vaccinated, compared to 47% of white LGBTQ adults, 42% of all LGBTQ adults, 39% of Latinx LGBTQ adults, and 39% of the general adult sample population.

Of all the groups included in HRC’s survey, Black LGBTQ men and transgender women experience the highest rates of HIV seroconversions in the U.S., though this does not offer much insight into the state of how PLWH feel about the vaccine. Currently, Perry N. Halkitis, Ph.D., M.S., M.P.H., dean of the Rutgers School of Public Health and director of the Center for Health, Identity, Behavior, and Prevention Studies, is conducting a study that is specific to how PLWH feel about the vaccine.

In a discussion about his ongoing research with the American Journal of Managed Care, Halkitis pointed to potential wariness toward the vaccine from PLWH who lived through the AIDS epidemic and early days of antiretroviral therapies (ARTs). Even without quantifiable data, there is good reason why anyone who was required to use the first generation of ART might feel hesitant toward vaccinations.

Though ART has come a long way since the early days of the AIDS epidemic, it cannot be forgotten that when the therapies first hit the scene, they were noted for causing severe side effects that, for some people, were as bad as the symptoms of HIV itself. Indeed, health activist Michael Callen once referred to the first antiretroviral, zidovudine, more commonly known as AZT, as “Drano in pill form.”

After testifying before the Presidential Commission on the HIV Epidemic in 1988, he told a reporter, “The overwhelming amount of people I know on AZT end up having to go off it, and in my opinion being sicker than when they started.”

Early side effects from ART included extreme weight gain or loss, fat redistribution, nausea, diarrhea, insomnia, severe fatigue, heart disease, bone loss, T-cell loss, memory loss, and sexual dysfunction. When used on its own, dosages of AZT prescribed to suppress HIV’s ability to replicate proved toxic to humans. Despite this, the drug was approved by the United States Food and Drug Administration (FDA) to combat HIV on March 19, 1987, after the completion of a single large-scale clinical trial. That sole clinical trial ran from February to September of 1986 but was halted—according to government officials and a spokesperson for Burroughs Wellcome, the pharmaceutical company that developed the drug along with the National Cancer Institute—because 19 participants taking placebo had died, compared to one in the clinical group taking AZT, and continuing to give placebo would be considered unethical.

AZT was originally developed in the 1960s as a treatment for cancer but was rejected, as journalist Celia Farber revealed in an article written for SPIN magazine’s November 1989 issue, because of its toxicity and ineffectiveness against cancer. Despite knowing how severely the drug affected people taking it, the drug was used on AIDS patients under the rationale that they were going to die anyway.

In Farber’s story, Brad Stone, the FDA’s spokesperson at the time, is quoted as saying, “The people in that [FDA panel] meeting approved the drug because the data [Burroughs Wellcome] had produced proved it was prolonging life. Sure it was toxic, but they concluded that the benefits clearly outweighed the risks.” This approval was granted over panel chair Itzhak Brook, M.D.’s objection that “The data is just too premature, and the statistics are not really well done. The drug could actually be detrimental.” Brook added later that he was “struck by the fact that AZT does not stop deaths. Even those who were switched to AZT still kept dying.”

Brook’s objection proved well-founded. As Farber notes in her reporting, in December 1988, The Lancet published a study that Burroughs Wellcome and the National Institutes of Health (NIH) chose not to include in their press kits. This study was conducted at Claude Bernard Hospital in Paris and went further than the original AZT trial. Whereas Burroughs Wellcome called their results “overwhelmingly positive,” the French doctors labeled their deeper studies “disappointing,” finding that AZT was too toxic for most to tolerate, had no lasting effect on HIV blood levels, and left the patients with fewer T-4 cells than they started with.

Though the French doctors noticed an initial clinical improvement, they concluded that “by six months, these values had returned to their pretreatment levels, and several opportunistic infections, malignancies, and deaths occurred.”

“The Least Effective in Lowering Viral Load”

This history was delved into further in a June 1993 Los Angeles Times story, “Toxic Hope: Widely Embraced, the AIDS Drug Is Now Under Heavy Fire: The AZT Story.” In her reporting, journalist Linda Marsa revealed that up until 1991, 80% of the $420 million dollars that had been invested into the NIH’s AIDS Clinical Trials Group was devoted to studies on AZT. Because of this preponderance with AZT, six years passed before clinical trials involving people and other HIV drugs, such as protease inhibitors, began.

This eventual shift away from AZT was fortuitous because by September 1995, a study described in AIDS Treatment News proved that when used as a monotherapy instead of in combination with other drugs, AZT “proved to be the least effective in lowering viral load when compared to the combinations.” But even as these newer generations of therapies were an improvement over AZT, the drugs still carried devastating side effects for some, demanded strict adherence guidelines concerning when and how they were taken, and could entail swallowing up to 30 pills in a single sitting, numerous times throughout the day.

Because of their exhausting side effects, Department of Health and Human Services (HHS) guidelines for asymptomatic individuals suggested that HIV treatment initiation be delayed for as long as possible, or down to the moment when a person’s CD4 count had plummeted to 200. In 1998, optimism about improving drugs led to new guidelines that suggested individuals “hit hard, hit early” with their treatment. However, by 2001, continuing side effects and treatment fatigue moved the HHS to revert to its earlier recommendations.

This consideration shifted yet again, especially after Atripla, the first single-tablet treatment regimen for HIV, made up of three different drugs (efavirenz, emtricitabine, and tenofovir disoproxil fumarate), was approved by the FDA in July 2006. However, the suggestion to begin HIV treatment as soon as possible did not become official until May 2015, when the NIH announced that a global study―launched by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) at 215 sites in 35 countries―concluded that individuals living with HIV “have a considerably lower risk of developing AIDS or other serious illnesses if they start taking antiretroviral drugs sooner, when their CD4+ T-cell count … is higher, instead of waiting until [it] drops to lower levels.”

Still a Bitter Pill to Swallow

The current-generation ARTs have been refined to the point that many people are able to use them without experiencing any side effects. Even with these improvements, research continues to study the long-term effects of taking a major medication. Just as pressingly, though there are now drugs, such as PrEP (pre-exposure prophylaxis) to prevent HIV transmission in seronegative people, there is still no vaccine or cure for the virus.

When speaking about the COVID-19 vaccine with LGBTQ people and PLWH, doctors and medical providers should keep this dire history in mind and be prepared with facts about how the development of the COVID-19 vaccine differed from the way that early ARTs were created. For instance, acknowledge that, like AZT, the COVID-19 vaccines were created very quickly, but remind patients that, unlike AZT, nearly every major scientific and medical institution in the world poured their energies into developing it.

It is also instructive to reflect that, as was previously reported by TheBody, compared to the COVID-19 vaccine, funding for early HIV medications was paltry. For instance, in 1985, then-president Reagan committed $126 million toward curing HIV (approximately $307 million in today’s money). Last May, the U.S. government’s Operation Warp Speed committed nearly $10 billion toward developing a COVID-19 vaccine. By August, the program had paid $2.1 billion to Sanofi and GSK, $1.2 billion to AstraZeneca, $1.95 billion to Pfizer, $1.6 billion to Novavax, $1.5 billion to Moderna, and $2 billion to Johnson and Johnson to develop their investigative vaccine candidates. That investment continued to grow to $18 billion, in addition to $3 billion being invested into developing antiviral pills to treat early infection with COVID-19.

By contrast, in March, Jeffrey E. Harris, M.D., Ph.D., a physician and economist at Massachusetts Institute of Technology, revealed in an article published by National Bureau of Economic Research that from 2000 to 2019, public and private funders had only spent approximately $15.3 billion dollars on research for potential HIV vaccines.

If the funding, time, and resources that have been allocated to fighting COVID-19 were applied to HIV, it is likely that we would have a vaccine in a relatively short amount of time. While that is a bitter pill to swallow, it is also an indication that in this world, run by capitalism as it is, we can safely trust the efficacy of the COVID-19 vaccine regardless of one’s HIV status, particularly when one remembers the horrors of early ART.