WHY NO ICING ON ARV CAKE?

Sir,

One of the best things about being a child is birthday parties. And what is a birthday party without a cake? Even for an adult a surprise birthday party or a dinner out with family or friends can be highlighted by the tradition of singing Happy Birthday and blowing out all the candles on the cake. Such memories. But did anyone ever get a birthday cake with candles but no icing on the cake? 

Highly doubtful. Who would ever forget to ice the cake? No one.  If it is not obvious yet, we live in the Age of Pandemics. This dawned 40 years ago when AIDS suddenly appeared, approximately 20 years after vaccines had almost vanquished polio. 

Pandemics have ravaged humanity since before the Black Plague of 16th Century Europe. Smallpox, polio, tuberculosis, and influenza cut swaths through populations leaving families, cities, and nations poorer. Some pandemics arrive, last a year or so and vanish, not to return for another century or two. 

Globe

Others like influenza continue circling the globe, mutating as they go. Many scientists think COVID-19, caused by the SARS-Cov-2 virus, will become an annual nuisance like influenza and people will have to take an annual corona vaccination to prevent re-infection. 

Most pandemics arise from the unseeable world of viruses, new ones emerging from the biome when least expected. Epidemics like Ebola, Zika, SARS or MERS appear and before you know it, they are gone, often suppressed through the diligent work of the World Health Organization (WHO) and national centres for disease control - CDCs.    

Some epidemics appear suddenly, cause panic and before you can say abracadabra they disappear. Others like HIV and tuberculosis linger for decades, even centuries. While HIV/AIDS has been the most devastating new disease of our lifetime, for the last four centuries tuberculosis has killed more people on Earth than any other disease – up to 25 per cent of all those who have lived during that time. That includes my grandmother. While people continue to celebrate birthdays and lead productive, loving, successful lives; far too many have been cut down in the prime of life due to HIV, TB or COVID-19 with far too few candles on their birthday cakes.

Blindsided 

Although scientists have made huge strides improving HIV therapy, they continue to be blindsided when previously unknown viruses arise and therapeutics developed specifically for one viral wave are ineffective when the next microbial wave rolls in to knock humanity off its feet. Why? Are scientists missing something? Did a piece of the scientific puzzle fall off the table and go missing? Or did researchers just forget to put the icing on the antiviral cake?  I first became interested in HIV therapies when there were no drugs to treat AIDS. 

When the scientist met me in a cramped windowless room at the Multi-Centered AIDS Cohort Study - MACS – at UCLA in Los Angeles, California in 1985 she informed me, “You are HIV positive. 

Drgus

As you know, there are no drugs to treat this disease and we may never have a drug to treat this disease because we have never had a drug that could treat a retrovirus.” OK I thought, I may have five years to live if I am lucky. What am I going to do? At that moment I had no idea.   

Today ARV drugs are more effective with fewer side effects and easier to take than ever. The most exciting leap forward came in 1996 at the International AIDS Conference in Vancouver, Canada when protease inhibitors were announced. The protease inhibitor class of drugs stopped the mass dying. The veil of desperation, tears, and premature death of the early AIDS Crisis finally lifted. The crying could stop - at least in America, Europe and the advanced industrialized countries that could afford the expensive new drugs. As usual, Africa had to wait. It waited nearly twenty years for AZT and more than a decade for protease inhibitors to arrive. A few in Africa are still waiting.   

Built

The pharmaceutical industry built its layer cake of antiretroviral drugs – ARVs – one layer at a time. The first layer was reverse transcriptase inhibitors (RTIs) - then improved RTIs. The second cake layer was protease inhibitors (PIs) - then improved PIs. The third layer includes integrase inhibitors and fusion inhibitors. The most profitable industry in the world, built a therapeutic cake for HIV that was highly effective, generally affordable, available to most people and easy to take. As Dr Pangloss in Voltaire’s Candide would have proclaimed, “It is the best of all possible therapeutic cakes.” 

Despite modern day Dr Panglosses assuring us otherwise, HIV therapeutics are not yet perfect for all. Approximately five per cent of AIDS patients never recover adequate immune function. Newer waves of pandemics continue to roll towards shore including Ebola, Zika, COVID-19 and, still out to sea, COVID-25, plus other unimagined ones. The continuing failure of doctors, scientists, governments, and the WHO to address the problem of the uniced cake of HIV therapy is a major setback in our understanding of how to defend humanity from the next viral onslaught.   How many beloved people will not live to blow out another set of candles due to viral pandemics? As the poet Bob Dylan sang, “The answer my friend is blowing in the wind. The answer is blowing in the wind.”           

Howard Armistead       

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