Today, I am thankful for all those who have ardently toiled over the last 40 years to fight the most devastating epidemic the world has witnessed in our lifetime.
The early years of the HIV epidemic were indeed an era of uncertainty, filled with worrisome unrest. It all started in June 1981, when the CDC reported 5 cases of a rare pulmonary infection, Pneumocystis carinii pneumonia (PCP), in young, gay men in California. That same day, a dermatologist called the CDC to inform them that he has observed a rare, aggressive malignancy – Kaposi sarcoma (KS) – in several gay men living in New York City. In due time, other opportunistic infections would be reported in similar patient populations, all in the setting low white blood cell count. Nearly 15 months later, the CDC would coin the term ‘AIDS’ to describe the syndrome. A little more than 2 years later, on this exact day (Apr 23) in 1984, the discovery of the virus responsible for causing acquired immune deficiency syndrome, or AIDS, would be announced by Margaret Heckler, US President Reagan's Secretary of Health and Human Services - a discovery credited to a few French virologists, led by Luc Montangier. By 1984, a group of scientists at Burroughs-Wellcome, collaborated with scientists at the National Cancer Institute (NCI) to identify that a nucleoside analogue, zidovudine (AZT), was a potent inhibitor of a key enzyme of HIV. Sadly, the benefit of AZT monotherapy was short-lived, as viral resistance to the NRTI would eventually occur, rendering AZT monotherapy ineffective in the long run.
Over the next decade, the diligent work of chemists across the pharmaceutical industry led to the development of the class of protease inhibitors (PI), a new drug to to be used in combination with NRTIs. By February 1996, the results of a study demonstrated the use of a PI (indinavir) in combination with 2 NRTIs (AZT and lamivudine [3TC]) worked significantly better than monotherapy with NRTIs. In due time, a larger study would further confirm that a triple combination was associated with improvement in survival and a reduction of opportunistic infections.
Yet, the field did not stop there. We saw the advancement in a new class of medicines, the non-nucleoside reverse transcriptase inhibitor (NNRTI), with the discovery of efavirenz in 1998. A decade later, the field was propelled further forward with the advent of the first integrase strand transfer inhibitor (InSTI), raltegravir. People living with HIV (PLHIV) can now expect
to have relatively normal lives with 6 to 7 decades of life, provided they adhere to their daily ART regimens. In most developed countries, the mortality associated with HIV has also precipitously fallen. Moreover, once-daily regimens to prevent HIV acquisition using pre-exposure prophylaxis (PrEP) are now routinely administered to high-risk populations.
But, the work on HIV is far from over. Why?
Since its inception, HIV and AIDS have claimed the lives of over 35 million people – a horrifying statistic. Currently, across the globe, nearly 37 million people live with HIV infection, and nearly 2 million new infections occur each calendar year. Moreover, nearly 1 million PLHIV will suffer an AIDS-related death in 2020. Around the globe (and even in the US), we are nowhere close to the UNAIDS 90-90-90 goal of having 90% of PLHIV fully diagnosed, 90% initiated on ART, and 90% with HIV fully suppressed in their blood. Efforts to cure HIV infection are also not on the immediate horizon. For this reason, the World Health Organization appropriately continues to list HIV as one of its top 10 threats to global health.
I’m grateful for all the advances the world has made to curb the HIV epidemic. But, the war is not over until we unlock the code that will lead to a definitive ‘cure’ to this dreadful disease. We should not and cannot rest on our laurels. We must keep pushing forward, despite the recent setbacks in HIV vaccine efficacy. As Thomas Edison once quipped, “When you have exhausted all possibilities, remember this: you haven’t.”
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