Are We Creating Drug-Resistant HIV?
The 23rd Conference on Retroviruses and Opportunistic Infections (CROI) opens today in Boston. For the next few days, thousands of scientists will report on the latest trends, threats, and hopes. Much attention likely will given to progress toward ending the HIV epidemic—a concept that no longer is a pipedream but now is an official government slogan.
Also certain to be a hotspot, and in direct contrast with the ambient optimism, will be discussion of the continued erosion of drug potency against the ever-mutable human immunodeficiency virus (HIV), the cause of AIDS. Charts and graphs and PowerPoint sleights of hand surely will be shown, fronted by sour 1950s faces, to demonstrate the doomsday scenario about to play out.
To insiders, this is part of what is called “drawing attention to the problem,” a staged melodrama of sorts. Because in fact, this exact hair-shirt fitting occurs at every meeting where the eternal battle between microbes and antimicrobials is featured.
It is the same sad story of potency lost, a victim of the old tenet that rules just about every product in every corner of commerce, be it antivirals or cars a new pair of dress shoes: If you use them, eventually they will fail. Like everything else in the market, antimicrobials are programmed to work wonderfully for a while then lose their collective grip, a victim of their own effectiveness. Maybe this year, maybe next year, maybe, like your father’s Toyota, 20 years from now, but fail they will because fail they must.
It is the nature of the drug-microbe tango: Antimicrobials fail because the enemy they are battling—a virus or some bacteria—has the relentless might of natural selection on its side. This means that sooner though hopefully later, because of the rapid winnowing by the drug of a population of a zillion viruses or bacteria, a genetic mutation will emerge that renders the very same drug near worthless.
A recent prominently featured report is a case in point. Last month in Lancet Infectious Diseases, researchers described features of HIV isolates collected from almost 2,000 patients scattered across 36 countries. Importantly, each of the patients in the study had already failed the standard treatment cocktail. To explain the lack of drug effectiveness, the scientists probed each HIV isolate to see whether genetic resistance mutations in the RNA of HIV itself could explain the situation.
And indeed mutations were the problem. Among the 2,000 patients, rates of resistance to an extremely useful and commonly prescribed drug in both treatment and prevention—tenofovir—ranged from about 20 percent of European isolates to more than 50 percent in many areas in Africa. In other words, people were using tenofovir across the world and, as a result, mutations resistant to tenofovir were emerging in a direct cause-and-effect fashion.
The report and others like it are pretty scary. Right now, we have two-dozen active drugs against HIV but they fall into only a half-dozen different drug classes; typically, drug resistance to one member of a drug class extends to the other members. So despite the apparent riches of the moment, when patients can be offered a single pill once a day with minimal side effects, we remain perilously close to real trouble.
Infectious disease and public health specialists often look at the still-deteriorating mess engulfing TB treatment as the ur-cautionary tale of bad public health funding and planning, bad understanding of biology, and extra-bad appreciation of how hard it is to take pills day after day. With TB too, we once seemed to have a deep bench with fresh classes of active agents that we barely had touched. But after a few decades of disorganized administration to the millions who were sick with the disease, we—humankind—did indeed run the table and create TB strains resistant to a dozen different anti-tuberculosis medications.
This recent calamity is behind the constant bellowing from all quarters as we confront an even more complex challenge with HIV and HIV meds. Tuberculosis, if treated correctly, can be cured by taking several medications regularly for six months; HIV by contrast requires daily medication for a lifetime, similar to the treatments for diabetes or high blood pressure.
To be sure, these issues comprise a substantial public health concern, one for experts to quietly debate and brood over. Yet the need is much less clear for the attendant talking head hyperventilation, self-blame about incorrect usage and pharmaceutical overreach, and overall panic in the streets (the Russians are coming! the Russian are coming!) proclaiming that the totally drug-resistant superbug is here.
After all, science—that product of the reasoned and the rational—does best in the cool deserted shade of evening. Placed into the midday glare with Donald and Miley and Oprah and their screaming headlines and wagging fingers, it slides into an embarrassed muddle and no longer is capable of showing us a steady light. So read this week’s dispatches from CROI carefully and with interest but realize that objects in the press are often much different than they appear.