Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV

A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.

Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV-infected patients is controversial. Demeter and colleagues evaluated this strategy in a randomized, open-label clinical trial, using a normalized inhibitory quotient (NIQ), which incorporates drug exposure and viral drug resistance. NIQs /=1000 copies/ml on a failing regimen, and began a new protease inhibitor containing regimen at entry. All FDA-approved protease inhibitors available during the study recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three participants with NIQ , were randomized at week 4 to standard of care (SOC) or protease inhibitor dose escalation (therapeutic drug monitoring). The primary endpoint was change in log10 plasma HIV-1 RNA concentration from randomization to 20 weeks later. Ninety-one patients were randomized to standard of care and 92 to therapeutic drug monitoring. NIQs increased more in the therapeutic drug monitoring arm compared to standard of care (+69 versus +25%, P = 0.01). Despite this, therapeutic drug monitoring and standard of care arms showed no difference in outcome (+0.09 versus +0.02 log10, P = 0.17). In retrospective subgroup analyses, patients with less HIV resistance to their protease inhibitors benefited from therapeutic drug monitoring (P = 0.002), as did black and Hispanic patients (P = 0.035 and 0.05, respectively). Differences between black and white patients persisted when accounting for protease inhibitor susceptibility. There was no overall benefit of therapeutic drug monitoring. In post hoc subgroup analyses, therapeutic drug monitoring appeared beneficial in black and Hispanic patients, and in patients whose virus retained some susceptibility to the protease inhibitors in their regimen.

Editors’ note: Although the authors state that they compared differences between the therapeutic drug monitoring group and the standard of care group with respect to the primary endpoint (change in viral load after 20 weeks) in specific sub-groups of patients according to sex, race and ethnicity, number of protease inhibitors in the study regimen, and whether fos-amprenavir was used) no data are provided for women who constituted 13% of the study participants. This is another example of the ‘fugitive data issue’ that the Women and Trials movement has identified as problematic. Authors need to make an extra effort to publish these data, as not enough is known about sex differences in pharmacokinetics and pharmacodynamics