Let’s be realistic: Every drug has potential or unavoidable side effects, and some may even make you puke. (Literally.)

Or you may feel so nauseated you don’t want to leave your bed. Or you may break out in hives. A new analysis from researchers at the University of Pittsburgh Graduate School of Public Health proposes HIV drugs, which often have severe side effects, would have greater impact if their toxicity level were lowered and patients began taking them sooner. "The side effects of treatment remain one of the primary reasons that HIV drug regimens are discontinued," said Dr. Mark Roberts, professor and senior author of the study. "By decreasing the toxicity and side effects of HIV drugs, you increase the amount of time that patients can stay on that life-saving treatment regimen.”

When Is It Best To Begin Taking Pills?

One of the biggest stumbling blocks for people living with HIV is medication adherence — sticking to their drug regimen. Antiretroviral therapy (ART) typically consists of a daily cocktail of at least three drugs, yet missing a pill or two may lead to eventual drug resistance. Since the highly toxic drugs often have side effects, many patients do not adhere to their regimen. For this reason, doctors take special care in timing when a patient begins ART, considering many factors, including age, gender, and viral load, in order to maximize a patient’s adherence and “quality‐adjusted life expectancy.” This term, along with "quality-adjusted life years" are measures used by pharmacologists and physicians to determine the value of medical actions. A life-saving drug that is highly toxic and leaves a patient debilitated, for example, would have a lower value than a life-saving drug that doesn’t have the same side effects.  

Last year, the World Health Organization (WHO) revised its previous guidelines on treatment initiation, recommending all patients start treatment early instead of waiting until their viral loads become heavy (as was recommended in the past). Meanwhile, new HIV drugs are approved each year, changing the available options for doctors and their patients. For the current study, then, the researchers used a computer simulation to explore WHO’s new recommendation in light of two untested factors: the fast rate of new drug development and drug toxicity. Would the simulation support WHO’s early treatment suggestion?

In a word: Yes. If new HIV drugs are less toxic than existing drugs, the simulation revealed, the new drugs will increase the patient's quality-adjusted life expectancy by as much as 11 percent — more than three years. Examing current drug toxicity levels, the researchers ran another simulation and discovered young patients would add nearly two years to their lives if they initiated ART soon after becoming infected instead of waiting as recommended in the past.

"This availability of new drugs means that as the drugs a patient is on become less effective, doctors can adjust the therapy to use a new, more effective drug," Roberts said. "And if that new drug has a low toxicity and is well-tolerated by the patient, then they are more likely to take it regularly so that it is as effective as possible."

 

Source: Khademi A, Braithwaite RS, Saure D, Schaefer AJ, Nucifora K, Roberts MS. Should expectations about the rate of new antiretroviral drug development impact the timing of HIV treatment initiation and expectations about treatment benefits. PLOS ONE. 2014.