Impact of drug levels and baseline genotype and phenotype on the virologic response to amprenavir/ritonavir-based salvage regimens.
Coadministration of amprenavir (APV) with small doses of ritonavir (RTV) results in a significant increase in APV plasma concentrations. Viruses showing resistance to other protease inhibitors (PI) may remain susceptible to APV, supporting a role for this drug in salvage therapy. We enrolled 35 patients who began a rescue intervention based on APV/RTV 600/100 mg twice daily. Their median viral load before beginning APV/RTV was 4.15 logs and their median CD4 count was 247 cells per microliter. The median prior PI exposure was of 43 months. At baseline, the median number of PI resistance mutations was 7. A significant virologic response (VR) (>1 log drop in plasma HIV-RNA and/or to <50 copies per milliliter) was recorded in 21.7% (5/23) of treated patients at week 48 (14.3% in the intent-to-treat analysis). The VR was significantly more frequent among subjects with less than 5 PI resistance mutations (66.6% vs. 5.8%; p = 0.008). Patients with prior exposure to lopinavir showed VR significantly less frequently than those not exposed to that drug (11% versus 60%; p < 0.05). The mean APV plasma trough concentration at week 12 was 1.3 microg/mL, and did not differ significantly comparing subjects having or not having VR. A trend toward a higher VR rate at week 48 was noticed among subjects with high genotypic inhibitory quotients (GIQ). In summary, HIV genotyping but not drug levels might be helpful to predict which patients would benefit from a rescue intervention based on APV/RTV 600/100 twice daily.
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Luisa
L
Valer
Daniel
D
González de Requena
Carmen
C
de Mendoza
Luz
L
Martin-Carbonero
Juan
J
González-Lahoz
Vincent
V
Soriano
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D005663:Furans; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D061466:Lopinavir; D008297:Male; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D018579:Patient Selection; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011744:Pyrimidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics; D019438:Ritonavir / Q000097:blood / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods*; D013449:Sulfonamides / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D019438:Ritonavir