As I was reading Mark Mascolini's report on the Second International Workshop on Salvage Therapy [titled "Salvage Solitaire (or, HAART takes a holiday)"] that graces this issue of the Journal, my desultory mind recalled the 1934 film Death Takes a Holiday. The classic story of Death taking on a human form to better understand life and why so many of us are reluctant to give it up, was recently regurgitated into another forgettable Brad Pitt showcase, Meet Joe Black.
While both versions of the hit Maxwell Anderson play of the 1920s portrayed Death as a man in love with an aristocratic woman, the original film with Frederic March as the vulnerable reaper tantalized our imagination with the romantic concept that no one could die when Death was in love. Death was too preoccupied with passion, and true passion suspends time. This subtext of a world without Death was captured in the promo for the 1934 film -- "The whole world waited while he made love."
Death Takes a Holiday could well serve as a title for the current state of HIV disease management in the world of the antiretroviral aristocrats -- that privileged seven percent of the global population with access to the expanding armamentarium of imperfect anti-HIV agents. However, in this instance, Death is not distracted by passion, but rather by the new mathematical mutation conundrum: How many antiretrovirals does it take to permanently suppress HIV? (a variation of the old antiethnic joke, "How many [fill in your favorite xenophobic epithet] does it take to change a light bulb?") The unfortunate answer at this milestone in anti-HIV drug development is "Never enough."
As Mascolini's report illustrates, our experience in using salvage regimens of combinations of four to as many as nine drugs are now commonplace, but our knowledge of pharmacokinetic interactions has not kept pace with our experimentation with exponential combinations of drugs. These are somewhat new frontiers in which the scientific and survival benefits of some salvage regimens may for some make life less worth living and Death more welcome.
Science, like the aristocratic object of Death's momentary passion, is also seductive. And like that luminous character originally played by Evelyn Venable in Death Takes a Holiday, science is also an aristocrat and as such is subject to an aristocratic ethic, which obligates itself to the needs of its own class. As important as it is to unlock the mysteries of the human immunodeficiency virus and better understand more effective ways of using our imperfect agents to extend the lives of those who are privileged to be antiretroviral aristocrats, there is also the noblesse oblige mandate for aristocrats to also attend to the needs of the millions of the poor without access to effective, inexpensive antiretroviral agents. Science may be serving its own aristocratic needs, but science has failed in its obligation to produce the more practical and less costly agents that could offer some promise of extended survival to the estimated 30 million HIV-infected men, women, and children who have a right to share in the benefits of scientific advances.
An ironic postscript to this metaphor of Death taking a holiday is that Death is only on holiday, and holidays by their definition are short-lived. Epistomologists tell us that one can never reach perfection through the cumulative addition of imperfections. If so, HIV may never be permanently suppressed by any combination of imperfect antiretrovirals or even in combination with imperfect immunomodulators or other new classes of drugs offering the promise of novel suppression mechanisms. For many, the antiretroviral Sirens that have distracted Death to date have lost their powers of enchantment, and Death returns to claim his own.
Gordon Nary is the Editor of the Journal.