HIV & Aging: Do Drug Concentrations Change With Age?
The answer appears to be yes—at least for some HIV meds.
In a UK study involving nearly 2,500 HIV-positive individuals aged 16 to over 50 years, concentrations of protease inhibitors (PIs) in blood plasma rose with increasing age, whereas concentrations of non-nucleoside reverse transcriptase inhibitors (NNRTIs) remained constant.
The strongest link between age and drug concentration in plasma was observed with the PIs ritonavir (Norvir) and saquinavir (Invirase). In addition, the researchers detected a small but statistically significant increase in PI drug concentration with each ten-year increase in age.
The study, reported by Alan Winston of Imperial College London and colleagues in the February 23, 2013, online edition of the Journal of Antimicrobial Chemotherapy, involved data on blood samples from 2,447 individuals in the Liverpool TDM Registry of HIV-positive individuals who had therapeutic drug monitoring as part of their routine care between 1999–2005 and 2008–2010. (Data were unavailable for the intervening years.) Data on clinical outcomes came from the large UK Collaborative HIV Cohort Study.
To explain their findings, the study team notes that most HIV protease inhibitors are taken with a “pharmacoenhancer”—another agent (usually ritonavir) that boosts drug levels by inhibiting the CYP450 enzyme system in the liver. CYP450 inhibition slows the body’s processing of the drug and thereby allows for greater drug exposure. Because liver function may decline with increasing age, the researchers state, “the effects of CYP450 enzyme inhibition may be greater in older individuals.” In other words, the “boost” given by pharmacoenhancing agents like ritonavir may increase as liver function wanes with age.
What do these increases in drug exposure mean clinically? Not much, in this initial analysis at least. The researchers observed no correlation between drug concentrations and markers of liver function used to assess drug toxicity. They also report that increased age was associated with a longer time before a given treatment was altered due to “viral failure” (failure of a drug regimen to keep the virus suppressed) or for other reasons. “The clinical relevance of this observation merits further investigation,” the article abstract concludes.
Given that older people living with HIV/AIDS (PLWHA) represent a growing population, studies like this one are much needed. “Winston and colleagues’ study helps us as we try to form a better understanding of how HIV treatment might need to be tailored as people with HIV/AIDS begin to live longer,” observes clinical pharmacist (and BETA columnist) Jennifer Cocohoba of the University of California, San Francisco. “Further research on this subject, done in different populations, will help guide clinicians on how to incorporate these findings into practice in the future.”
And while these study findings may ultimately help fine-tune antiretroviral therapy for older adults, they certainly shouldn’t prompt folks to cut back on their own PIs: Adds Cocohoba, “PLWHA currently taking protease inhibitors should not change their doses of anti-HIV medicines without first discussing with their treating clinician.” If you’re concerned, don’t be shy about talking with your doc about this study and ways to optimize your own treatment regimen.
Reilly O’Neal is a freelance writer and former editor of BETA.
Centers for Disease Control and Prevention. HIV/AIDS among Persons Aged 50 and Over.
Winston, A. and others. Effects of age on antiretroviral plasma drug concentrations in HIV infected subjects undergoing routine therapeutic drug monitoring. Journal of Antimicrobial Chemotherapy. February 23, 2013 (Epub ahead of print).