Drug Concentration Control Provides No Apparent Help in HIV Salvage Therapy

There appears to be no significant improvement in outcome of HIV salvage therapy when drug dosages are based on a concentration-controlled intervention (CCI) protocol -- whether the drug selection is guided by rules-based HIV-1 genotype drug-resistance interpretation (GI) or by virtual phenotype drug-resistance interpretation (VPI) -- Italian researchers report in the June 15th issue of Clinical Infectious Diseases.

Dr. Carlo Torti of the Institute for Infectious and Tropical Diseases, Brescia, and colleagues note that it is not well defined which of the two main ways of interpreting genotypic drug resistance tests -- GI or VPI -- might be best for HIV salvage therapy.

Also, monitoring and adjusting dosage based on plasma concentrations -- CCI -- has not been shown to improve efficacy in prospective studies.

To investigate further, the researchers conducted a prospective trial of 230 patients on failing regimens. They were randomized to change treatment after either GI or VPI. They were then further randomized to a control group or to receive CCI.

Virological benefit did not differ significantly across groups, although there was a non-significant advantage in those given CCI compared to controls.

At week 4, response amounted to 56.8% of patients with an HIV RNA load above 400 copies per mL in the CCI group versus 64.3% in the control group. Corresponding values at week 12 were 63.6% and 74%.

The researchers note that although medication adherence was higher in the CCI group, dose adaptation was possible only in a fraction of patients overall because of poor treatment adherence or patient refusal to increase doses.

Among independent predictors of virologic response at the end of the 24-week study were higher plasma trough concentrations of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors. This was also true of regimens containing PIs boosted with ritonavir.

The researchers conclude that the results do not support routine use of CCI, but they suggest that practical obstacles such as the lack of patient compliance may have influenced these findings.

06/08/05

Clin Infect Dis 2005; 40:1828-1836.

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