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High Indinavir Plasma Concentrations in HIV-1 Patients Co-infected with Hepatitis B or C Virus Receiving Indinavir and Ritonavir Low Dosages: A GENOPHAR Substudy
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This study presented at the Retrovirus Conference (abs 546, Feb 10-14, 2003, Boston) examined 6 patients in the GENOPHAR Study who were coinfected with HIV and chronic HBV or HCV. In this study patients received the PI combination of indinavir 400mg twice daily boosted by 100 mg of ritonavir twice daily. The study found that in these 6 coinfected individuals indinavir blood concentrations were very high. In all patients a viral load of <200 copies/ml was obtained. Despite the high levels of indinavir no side effects were reported. Within one month regimen was changed to 200mg IDV and 100mg RTV in these 6 patients; adequate IDV Cmin was obtained and remained stable through the 24 weeks of the study. HIV viral load remained undetectable until the end of the study. The authors concluded that this low dose of 200/100 appears to be effective and safe in coinfected patients. However, there is no report in the abstract on what stage of liver disease these 6 patients were at. Did they have stage 3 or 4 more advanced disease where the liver might be less functional thus leading to higher IDV drug levels or did they have earlier stage disease where the liver may be more functional leading to more normal IDV drug levels.
Abstract-To evaluate the efficacy and safety of the combination of indinavir/ritonavir (IDV/RTV) low dose (400/100 mg bid) with two NRTI in patients (pts) with chronic HepatitisC (HCV) or Hepatitis B (HBV). We have analyzed this combination in pts co-infected with HIV and either HBV (HBs antigen-positive) or HCV (HCV RNA-positive) in the GENOPHAR Study. The objective of the GENOPHAR Study was to evaluate, in the context of an expert committee advice, the benefit of TDM in association with genotypic resistance testing to optimize treatment in multi-experienced pts. A total of 134 pts have been enrolled in this study, including 24 pts co-infected with HIV-1 and either HBV (n = 10) or HCV (n = 14). In 5 pts with HCV, 1 with HBV and 16 without chronic hepatitis (control group), treatment with IDV/RTV low doses (400/100 mg bid) combination plus 2 NRTI was selected upon results of the resistance genotyping test, treatment history, and drug tolerance. A month after starting the new regimen, HIV-1 RNA level was measured and IDV Cmin was performed by using a HPLC assay. We considered plasma concentrations as adequate if values of IDV Cmin determined 12 hours after the last intake were in the therapeutic range of 150 to 675 ng/mL.
In the 6 pts with chronic hepatitis, IDV plasma concentrations were very high, and all Cmin but one were < 675 ng/mL (median value: 1,440 ng/mL; range: 650 to 2,310 ng/mL). In all pts, a viral load < 200 copies/mL was achieved. Despite high IDV Cmin in these pts, no side effect was noted.
After a therapeutic adjustment within a month (IDV/RTV 200/100 mg bid), adequate IDV Cmin were obtained and remained stable in 5 pts until the end of the study (at week 24: median value: 277 ng/mL; range: 150-320 ng/mL). The pt with HCV, who had an adequate Cmin, was lost to follow-up. HIV-1 RNA level remained undetectable until the end of the study. In the control group (n = 16), all but 3 pts had IDV Cmin within adequate values (median value: 422 ng/ml; range: 150-2,512 ng/ml). After treatment adjustment (IDV/RTV 200/100 bid), adequate plasma concentrations were obtained in the remaining 3 pts. In conclusion, the results of this study suggest that the IDV/RTV low dose (200/100 mg bid) appears to be effective and safe in pts co-infected with HIV and HCV or HBV. The benefit of TDM in association with genotypic resistance testing and expert advice to optimize subsequent therapy in HCV or HBV co-infected pts receiving the combination IDV/RTV appeared crucial in this GENOPHAR substudy.
Abst. 546. Retrovirus Conference 2003, Feb 10-14. P. Bossi et al. Pitie-Salpetriere Hosp, Paris, France and Bichat-Claude Bernard Hosp, Paris, France
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