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GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy.
HIV Med. 2004 Sep; 5(5):352-9.HM

Abstract

OBJECTIVES

To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1.

METHODS

Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load<200 copies/mL at week 12.

RESULTS

A total of 134 patients were randomized in the study, with 67 in each group, and included in the intent-to-treat (ITT) analysis. At baseline, median values were as follows: viral load (log(10) copies/mL): G=4.1, GP=4.0; CD4 cell count (cells/microL): G=292, GP=294; and number of prior drugs: G=7, GP=8. The median number of resistance mutations was five in the G group [nucleoside reverse transcriptase inhibitors (NRTIs)=three; non-nucleoside reverse transcriptase inhibitors (NNRTIs)=one; protease inhibitors (PI)=one] and seven in the GP group (NRTI=four; NNRTI=two; PI=one). At week 8, treatment was adjusted according to the TDM in 13 of the 67 patients in the GP group (19%). By ITT missing equal failure analysis at week 12, and after only one intervention according to plasma concentration results, a viral load<200 copies/mL was achieved in 30 of the 67 patients (45%) in the G group and in 29 of the 67 patients (43%) in the GP group (not significant). In the multivariate analysis, only prior exposure to at least two PIs at baseline gave a poor response to subsequent antiretroviral therapy. At week 24, a viral load<200 copies/mL was achieved in 35 of the 67 patients (52%) in the G group and in 40 of the 67 patients (60%) in the GP group.

CONCLUSIONS

A statistically significant benefit of using TDM was not found in this short-term study where patients appeared to be adherent. However, combining genotypic resistance testing with the use of an expert committee to monitor subsequent therapy individually in patients with multiple resistance mutations was associated with high antiviral efficacy.

Authors+Show Affiliations

Department of Infectious Diseases, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, 75013 Paris, France. philippe.bossi@psl.ap-hop-paris.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15369510

Citation

Bossi, P, et al. "GENOPHAR: a Randomized Study of Plasma Drug Measurements in Association With Genotypic Resistance Testing and Expert Advice to Optimize Therapy in Patients Failing Antiretroviral Therapy." HIV Medicine, vol. 5, no. 5, 2004, pp. 352-9.
Bossi P, Peytavin G, Ait-Mohand H, et al. GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy. HIV Med. 2004;5(5):352-9.
Bossi, P., Peytavin, G., Ait-Mohand, H., Delaugerre, C., Ktorza, N., Paris, L., Bonmarchand, M., Cacace, R., David, D. J., Simon, A., Lamotte, C., Marcelin, A. G., Calvez, V., Bricaire, F., Costagliola, D., & Katlama, C. (2004). GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy. HIV Medicine, 5(5), 352-9.
Bossi P, et al. GENOPHAR: a Randomized Study of Plasma Drug Measurements in Association With Genotypic Resistance Testing and Expert Advice to Optimize Therapy in Patients Failing Antiretroviral Therapy. HIV Med. 2004;5(5):352-9. PubMed PMID: 15369510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GENOPHAR: a randomized study of plasma drug measurements in association with genotypic resistance testing and expert advice to optimize therapy in patients failing antiretroviral therapy. AU - Bossi,P, AU - Peytavin,G, AU - Ait-Mohand,H, AU - Delaugerre,C, AU - Ktorza,N, AU - Paris,L, AU - Bonmarchand,M, AU - Cacace,R, AU - David,D-J, AU - Simon,A, AU - Lamotte,C, AU - Marcelin,A-G, AU - Calvez,V, AU - Bricaire,F, AU - Costagliola,D, AU - Katlama,C, PY - 2004/9/17/pubmed PY - 2004/12/16/medline PY - 2004/9/17/entrez SP - 352 EP - 9 JF - HIV medicine JO - HIV Med VL - 5 IS - 5 N2 - OBJECTIVES: To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1. METHODS: Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load<200 copies/mL at week 12. RESULTS: A total of 134 patients were randomized in the study, with 67 in each group, and included in the intent-to-treat (ITT) analysis. At baseline, median values were as follows: viral load (log(10) copies/mL): G=4.1, GP=4.0; CD4 cell count (cells/microL): G=292, GP=294; and number of prior drugs: G=7, GP=8. The median number of resistance mutations was five in the G group [nucleoside reverse transcriptase inhibitors (NRTIs)=three; non-nucleoside reverse transcriptase inhibitors (NNRTIs)=one; protease inhibitors (PI)=one] and seven in the GP group (NRTI=four; NNRTI=two; PI=one). At week 8, treatment was adjusted according to the TDM in 13 of the 67 patients in the GP group (19%). By ITT missing equal failure analysis at week 12, and after only one intervention according to plasma concentration results, a viral load<200 copies/mL was achieved in 30 of the 67 patients (45%) in the G group and in 29 of the 67 patients (43%) in the GP group (not significant). In the multivariate analysis, only prior exposure to at least two PIs at baseline gave a poor response to subsequent antiretroviral therapy. At week 24, a viral load<200 copies/mL was achieved in 35 of the 67 patients (52%) in the G group and in 40 of the 67 patients (60%) in the GP group. CONCLUSIONS: A statistically significant benefit of using TDM was not found in this short-term study where patients appeared to be adherent. However, combining genotypic resistance testing with the use of an expert committee to monitor subsequent therapy individually in patients with multiple resistance mutations was associated with high antiviral efficacy. SN - 1464-2662 UR - https://www.unboundmedicine.com/medline/citation/15369510/GENOPHAR:_a_randomized_study_of_plasma_drug_measurements_in_association_with_genotypic_resistance_testing_and_expert_advice_to_optimize_therapy_in_patients_failing_antiretroviral_therapy_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=1464-2662&amp;date=2004&amp;volume=5&amp;issue=5&amp;spage=352 DB - PRIME DP - Unbound Medicine ER -