February 4, 2009

Therapeutic Drug Monitoring May Benefit People of Color

Adjusting a person’s dose of protease inhibitor (PI) based on his or her blood levels of the drug—called therapeutic drug monitoring (TDM)—may improve treatment responses in black and Hispanic people with HIV, according to a study published in the January 28 issue of AIDS. Though TDM failed to show an across-the-board benefit for most patients, it did appear, paradoxically, to work best in people with the least amount of drug resistance.

It has been noted for more than a decade that blood levels of PIs can vary a great deal from person to person. Scientists have long wondered to what degree this could help explain why new PI regimens sometimes fail more quickly in some people. Earlier studies have been unable to find a benefit from adjusting doses based solely on a person’s trough level—the lowest blood level of the drug just before a person takes his or her next dose—which is determined using TDM. Some researchers have proposed that TDM might work better if two numbers are taken into consideration when making dose changes: the trough level as well as the minimum amount of drug needed to neutralize HIV found in previous studies of people on the drugs. Considered together, both numbers form a ratio, known as the normalized inhibitory quotient or NIQ.

To determine whether drug monitoring and dose adjustment based on NIQ may be more successful, Lisa Demeter, MD, from the University of Rochester School of Medicine and Dentistry in New York State checked drug levels in 183 people with HIV who had just started a new PI-based regimen. About half made dosing changes, if necessary, based on NIQ results, whereas the remaining patients continued on the normal dose of their PI regardless of drug blood levels. An additional 50 people who had high blood levels of the drugs comprised a third group added for observation.

When Demeter’s team analyzed all groups, those who altered their PI dosing based on NIQ results did not appear more likely to achieve or maintain undetectable HIV levels than those who did not make dosing changes. Interestingly, however, black and Hispanic patients, who made up just over half of both groups, did appear to benefit from TDM. Since there were no major differences between the black and Hispanic patients and the white patients in terms of body size or other parameters, race and ethnicity appear to be the primary reasons for the difference in treatment response.

Also of note, Demeter and her colleagues said that they would have anticipated that people who entered the study with more drug resistance would be the ones to benefit most from TDM, but the opposite appeared to be true. Thus, TDM may have maximized the impact of treatment in people with little existing PI resistance but may not have increased efficacy enough to overcome preexisting drug resistance.

Search: therapeutic drug monitoring, TDM, inhibitory quotient, NIQ, black, Hispanic, people of color, protease inhibitor, Lisa Demeter, University of Rochester School of Medicine and Dentistry

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