Patients refractory to HIV treatment require close monitoring

HIV-infected patients who have exhausted their options should receive close therapeutic drug monitoring, according to Dr. Patrick W. G. Mallon of the National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia.

Speaking here Thursday at the conference of the Australasian Society for HIV Medicine, Dr. Mallon described a study of 40 HIV-positive men who were followed at St. Vincent’s Hospital in Sydney. All had previously failed antiretroviral therapy. The aims were to determine the relationship of therapeutic drug monitoring to outcome in heavily pretreated patients, and determine the success rate of a pre-dose therapeutic drug monitoring protocol in routine clinical practice.

Dr. Mallon cited the weakness of a number of indicators, suggesting that, for instance, “NRTI [nucleoside reverse transcriptase inhibitor] levels give no indication of level of activity within the cell,” and that it is difficult and expensive to measure NRTI levels.

Based on genotype analysis, study participants were started on new regimens, consisting of boosted doses of protease inhibitors (amprenavir and/or lopinavir, with or without efavirenz). Twenty-four weeks later, the results were assessed via therapeutic drug level and virological response to lopinavir and efavirenz.

Dr. Mallon reported that “53% of the cohort achieved virological success. Lopinavir levels were lower than expected, at an average of 3543 µg/L, and efavirenz levels were comparable with previous reports, but without CNS toxicity in this study.”

For the future, Dr. Mallon suggested that general practitioners who are treating this patient population need to “look for a drug level within a certain range.” It is a major problem, he said, that these levels are not well defined.

He added that the other option would be to aim for the highest safe drug level. “This would be ideal,” he said, “for failing patients, and would lead to individualized drug therapy and regimes, but as the ranges have not been defined for different cohorts this cannot be safely done at this time.”

Source: Reuters Health

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