Musings on a Prior Pandemic, Part Three: The Medical Legacy of AIDS

In this three part series, Dr. Kenneth H. Mayer, Fenway Health Medical Research Director and Co-Chair of The Fenway Institute, reflects on the 40th anniversary of the AIDS epidemic.

Unlike the onset of the AIDS epidemic, where a specific date can be cited as to when the epidemic first became recognized around the world, it took more than a decade before adequate control could be envisioned. Everything has moved at warp speed in regard to the detection of SARS-CoV-2, the elucidation of the egologic agent of the COVID-19 pandemic, and the development of safe and effective vaccines. For HIV, the road to effective therapy was extremely bumpy, with initial drugs like AZT, being pulled off the shelf from the cancer chemotherapy armamentarium. Because HIV replicated wildly and widely, like cancer cells, a paradigm emerged that the maximum tolerated dose be used; the theory was to give the highest dose that humans can tolerate of one specific medication and see if that would eventually prevent the virus from replicating.

It turned out that single drugs were not sufficient. HIV would initially become inhibited, but would very quickly mutate, replicate and resume its destructive effect on the immune system. It took several years to develop second, third and fourth drugs that would be used in various two-drug combinations to no avail. These drugs would merely postpone the inevitability of the immune system succumbing to the effects of the virus. Several advances later helped us turn the corner around 1995-1996, particularly the ability to better quantify the development of new classes of agents that could be mixed and matched with some of the older drugs. That quantification process is known as Nucleic Acid Amplification Testing (NAAT).

Given that HIV does not grow well outside of the human body, and to grow it up in any quantities would be an infection control hazard for any worker, the development of NAAT technology was a major breakthrough. The ability to quantify the amount of virus in the blood meant that when people went on treatment, one could see how quickly the virus was suppressed and whether the viral suppression was sustained. This was a major advance over the prior way that clinical trials were done, in that waiting for decreases in immune cell counts or the development of clinical diseases could take many years and the clinical courses were variable for individuals. Having the direct ability to measure the amount of virus in the body allowed for very quick assessment as to whether drugs were working or not. The development of the protease inhibitors as a new class of agents was also a radical shift, in that it allowed clinicians to come up with combinations of medication that were more highly effective.

Since 1996, HIV care has used the same paradigm, but the insights around the disease have changed substantially. The discovery that prompt viral suppression through medication not only improves individual health and avoids immunosuppression, but also helps stop the spread of infection, has been a major insight that has led some optimists think that the AIDS epidemic could be controlled by getting everyone on treatment. That is easier said than done, given that by the time this was recognized, there were almost 40 million people living with HIV across the planet, with close to 2 million new HIV infections per year.

In addition to the sheer number of people who need treatment being huge, many HIV positive individuals may live in circumstances that make access to medication or regular adherence challenging, ranging from experiencing poverty, violence/victimization, unstable housing or lack of access to effective and affordable medical care. One of the major advances in the HIV epidemic was not medical, but rather political: the development of the PEPFAR (The President’s Emergency Program for AIDS Relief). President Bush and his congressional colleagues recognized that by doing nothing, millions in Africa would likely die despite the fact that safe medication was available. The PEPFAR program has supported the cost of antiretroviral therapy for more people than any other program on the planet and has been a major lifesaver. PEPFAR is one of the most definitive examples of how concerted action by the US in providing resources where they’re most needed can have a major impact on an epidemic, and should be an exemplar for the US response to COVID-19 globally.

The other dramatic change that was built out of the advances of scientific understanding about the role of antiretrovirals on viral replication was the recognition that antivirals are effective as prophylaxis to prevent HIV spread. Clinical trials have established the efficacy of pre-exposure prophylaxis (PrEP) in protecting against HIV infection, which complements the impact of effective treatment in decreasing infectiousness in people with HIV. Thus, over the last few years, a status neutral paradigm has emerged that suggests that to better control the HIV epidemic, we need to ensure anybody who has a risk for HIV has access to testing. If they test positive, they should be engaged in care and treatment as soon as feasible and have their needs addressed so they can maintain ongoing viral suppression. If they test negative, it is hoped that clinicians assess their risk and evaluate if they can benefit from PrEP.

Forty years on, we have an epidemic that can be controlled with antiretrovirals, in theory. However, the success of this is still dependent on access to resources to provide medications for those who need them, and is impacted by the many social, structural and behavioral challenges that impede optimal management of the AIDS pandemic.

In June of 2021, there are many lessons to be learned from four decades AIDS that pertain to the COVID-19 pandemic. If one were to distill three major take homes, they are:

1.) Science matters. That means that support for getting people trained to do science matters, support for innovative projects matters, and public support to promote scientific literacy matters because there are no such things as “alternative facts” – just facts. Facts are empirical; facts are not necessarily absolute. If new data and new facts are brought to bear, one may have to revisit prior understandings, but that doesn’t mean they don’t exist or they’re completely relative. Science is the creation of knowledge, and knowledge expands. Sometimes new insights create new facts, or new understandings.

2.) Discrimination is toxic, and by not addressing the upstream causes of discrimination at the outset, pandemics will only get worse. Homophobia, transphobia, sexism and racism have all played roles in perpetuating the HIV epidemic, driving many people to not be comfortable acknowledging their sexual orientation and therefore being unable to readily access healthcare. With COVID-19, the disproportionate impact on Black, Latinx and Indigenous people in the US is a testimony to the need to ensure more egalitarian society.

3.) We are in a global village and share a global gene pool. The HIV epidemic began in Central Africa and disseminated because of urbanization and increased global mobility. SARS-CoV-2 may have first appeared in China, but no country “owns” any virus or other pathogen. The patterns of dissemination of any of these wild beasts depend on human behavior, in addition to intrinsic properties of the organism. As we scale up to vaccinate increasing numbers of individuals in the United States against SARS-CoV-2, we must be well advised that the pandemic is not over until it’s over everywhere. Hopefully once a substantial proportion of the US population is vaccinated, increasing amounts of resources can be dedicated to getting everyone vaccinated across the world.

The legacy of AIDS reminds us of the need for epidemiologic humility. We need to have strong public health systems in place to help us anticipate and mitigate the next pandemic – because there will always be a next pandemic.

Read part one.

Read part two.

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