of protease inhibitors increase with age, investigators from the United Kingdom
report in the Journal of Antimicrobial
Chemotherapy. Each ten-year increment in age was associated with a
significant increase in concentrations of protease inhibitors in plasma. In
contrast, there was no association between age and plasma levels of
non-nucleoside reverse transcriptase inhibitor (NNRTI) levels.
“We have observed a
statistically significant association between standardized plasma drug
concentrations and protease inhibitors and age, with greater drug exposure
associated with increasing age,” write the authors.
treatment and care mean that the prognosis of most people living with HIV in the
UK is now excellent. It is known that the way in which the body processes medicines
changes as people age. However, relatively little is known about the
impact of ageing on plasma concentrations of antiretroviral drugs.
therefore designed a study involving 2447 people with HIV who had
therapeutic drug monitoring as part of their routine care between 1999-2005 and
2008-10. The impact of age on concentrations of protease inhibitors and NNRTIs was
analysed by the researchers. Data concerning liver function was
also studied to see if alterations in drug concentrations were accompanied by
an increased risk of toxicities.
A total of 3549
therapeutic drug monitoring samples were available for analysis. The majority
of these related to people aged between 35 and 50 years, and the fewest from
individuals aged over 50. This age profile reflected the demographics of people receiving HIV care in the UK.
Approximately 4% of
patients were co-infected with hepatitis B, 5% had hepatitis C co-infection and
30% of individuals had abnormal liver function.
Overall, 71% of
samples were from people taking protease inhibitor therapy, and 29% from people taking an NNRTI. The greatest number of concentrations were
assessed for lopinavir (Kaletra, 22%),
efavirenz (Sustiva, 19%), atazanavir (Reyataz,
17%) and saquinavir (Invirase, 12%).
As age increased, plasma
concentrations of NNRTIs remained largely stable.
Conversely, there was
a clear relationship between increasing age and increasing concentrations of
protease inhibitors (p = 0.033).
between age and plasma protease inhibitor concentrations remained significant
after adjusting for other factors. Each ten-year increase in age was associated
with an increase in protease inhibitor concentrations (p = 0.044).
Of all protease
inhibitors, the strongest associations between age and plasma levels were for
ritonavir (Norvir, p < 0.001) and
saquinavir (p = 0.015).
The authors speculate
that the relationship between increasing age and concentrations in protease
inhibitors is because they are metabolised using the P450 enzyme.
“Strengthening this hypothesis is our observation that a stronger effect of age
was observed between standardized plasma concentration of ritonavir
measurements compared with other protease inhibitors”, comment the authors,
There was no evidence
of a relationship between drug concentrations and liver toxicities. Indeed,
older age was associated with increased time to changing treatment for reasons
other than virological failure (p < 0.001).
The authors are unsure
of the clinical significance of their findings, but believe their results “may
assist in the design of future work assessing the effects of lifelong
antiretroviral therapy in subjects ageing with HIV infection.”