PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results.
OBJECTIVE
A randomized study to evaluate the usefulness of protease inhibitor (PI) therapeutic drug monitoring (TDM) in antiretroviral-experienced HIV-infected patients.


METHODS
In the control arm, treatment was modified according to genotypic resistance testing. In the TDM arm, therapy was modified on the basis of genotypic resistance testing and at week 8 according to PI plasma trough levels measured at week 4. The major endpoint was the change in HIV-RNA levels at week 12.


RESULTS
A total of 183 patients, 96 in the control arm and 87 in the TDM arm, were included in the study. Low-dose ritonavir to enhance the associated PI was prescribed to 62.5% of patients in the control arm and 65.5% of patients in the TDM arm. Using our PI concentration targets, 17/81 patients (21%) in the TDM arm were considered to have suboptimal or partly optimal PI plasma levels at week 4. Physician and protocol-driven PI modifications were performed in 18/85 patients (23.5%) in the TDM arm, and in seven of 94 patients (7%) in the control arm (P < 0.01). Week 12 HIV RNA dropped 2 log10 copies/ml in the control arm and 1.7 log10 copies/ml in the TDM arm, respectively.


CONCLUSIONS
We found no statistically significant difference between the TDM arm and control arm in virological outcome at week 12. The utility of TDM could be dependent on the presence of low-dose ritonavir as a booster and the antiretroviral experience of the studied population. Effective non-toxic target concentrations for resistant viruses have still to be determined.
Clevenbergh
Philippe
P
Infectious Diseases Department, CHU Nice, Nice, France. clevenberghph@hotmail.com
Garraffo
Rodolphe
R
Durant
Jacques
J
Dellamonica
Pierre
P
D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016037:Single-Blind Method
D017320:HIV Protease Inhibitors; D012367:RNA, Viral