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Jose R Arribas - One of the best experts on this subject based on the ideXlab platform.
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Switching to lopinavir/Ritonavir with or without abacavir/lamivudine in lipoatrophic patients treated with zidovudine/abacavir/lamivudine
The Journal of antimicrobial chemotherapy, 2013Co-Authors: Jose I. Bernardino, Federico Pulido, Esteban Martínez, Julio Arrizabalaga, P. Domingo, Joaquín Portilla, Antonio Ocampo, Jessica Muñoz, R. Torres, Jose R ArribasAbstract:BACKGROUND Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery. METHODS This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/Ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/Ritonavir plus abacavir/lamivudine versus lopinavir/Ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007). RESULTS Of 95 patients included, 88 were randomized to lopinavir/Ritonavir plus abacavir/lamivudine (n = 44) or lopinavir/Ritonavir monotherapy (n = 44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/Ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/Ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/Ritonavir plus abacavir/lamivudine, P = 0.09/0.07, versus +215/+416 g in the lopinavir/Ritonavir monotherapy group, P = 0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)]. CONCLUSIONS In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/Ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/Ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.
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drugs in traditional drug classes nucleoside reverse transcriptase inhibitor nonnucleoside reverse transcriptase inhibitor protease inhibitors with activity against drug resistant virus tipranavir darunavir etravirine
Current Opinion in Hiv and Aids, 2009Co-Authors: Jose R ArribasAbstract:Purpose of reviewThis review focuses on the use of tipranavir/Ritonavir, darunavir/Ritonavir and etravirine for the treatment of HIV infection that has become resistant to protease inhibitors and/or nonnucleoside reverse transcriptase inhibitors.Recent findingsTipranavir/Ritonavir and darunavir/rito
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Drugs in traditional drug classes (nucleoside reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor/protease inhibitors) with activity against drug-resistant virus (tipranavir, darunavir, etravirine).
Current Opinion in Hiv and Aids, 2009Co-Authors: Jose R ArribasAbstract:Purpose of reviewThis review focuses on the use of tipranavir/Ritonavir, darunavir/Ritonavir and etravirine for the treatment of HIV infection that has become resistant to protease inhibitors and/or nonnucleoside reverse transcriptase inhibitors.Recent findingsTipranavir/Ritonavir and darunavir/rito
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a 96 week comparison of lopinavir Ritonavir combination therapy followed by lopinavir Ritonavir monotherapy versus efavirenz combination therapy
The Journal of Infectious Diseases, 2008Co-Authors: William D Cameron, Jose R Arribas, Scott C. Brun, Martin S King, Barry Bernstein, Barbara A Da Silva, Robert Myers, Nicholaos C Bellos, Norbert Gilmore, George J HannaAbstract:Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/Ritonavir (n = 104) or efavirenz (n = 51). Lopinavir/Ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels <50 copies/mL started lopinavir/Ritonavir monotherapy. In previous-failure=failure analysis, 48% (lopinavir/Ritonavir) and 61% (efavirenz) maintained HIV-1 RNA at <50 copies/mL through week 96, (P = .17; 95% confidence interval [CI] for the difference, −29% to 4%); in noncompletion=failure analysis, 60% (lopinavir/Ritonavir) and 63% (efavirenz) maintained HIV-1 RNA at <50 copies/mL at week 96 (P = .73; 95% CI for the difference, −19% to 13%). Significant sparing of peripheral lipoatrophy was noted in the lopinavir/Ritonavir simplification strategy. This study has provided important information for future studies using treatment simplified to lopinavir/Ritonavir monotherapy.Trial registration. ClinicalTrials.gov identifier: NCT00075231.
R E Bawdon - One of the best experts on this subject based on the ideXlab platform.
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Placental transfer of Ritonavir with zidovudine in the ex vivo placental perfusion model.
American journal of obstetrics and gynecology, 1998Co-Authors: B M Casey, R E BawdonAbstract:The object was to determine the placental transfer of Ritonavir alone and in combination with zidovudine. Twelve placental perfusion studies were performed at trough (1-2 microg/mL) and peak (approximately 20 microg/mL) combinations of Ritonavir and zidovudine. Accumulation of Ritonavir was determined. Transfer of Ritonavir at trough concentrations was undetectable (<0.025 microg/mL). The clearance index of Ritonavir at peak concentration was 0.085 +/- 0.05 and was unaffected by zidovudine. The fetal concentration of Ritonavir was 0.0758 +/- 0.22 microg/mL at a maternal concentration of approximately 20 microg/mL and 25.5 +/- 6.9 microg/mL at a concentration of 100 microg/mL. There was no tissue accumulation of Ritonavir either alone or with zidovudine. The clearance index of Ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of Ritonavir.
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Placental transfer of Ritonavir with zidovudine in the ex vivo placental perfusion model
American Journal of Obstetrics and Gynecology, 1998Co-Authors: B M Casey, R E BawdonAbstract:Abstract OBJECTIVE: The object was to determine the placental transfer of Ritonavir alone and in combination with zidovudine. STUDY DESIGN: Twelve placental perfusion studies were performed at trough (1-2 μg/mL) and peak (~20 μg/mL) combinations of Ritonavir and zidovudine. Accumulation of Ritonavir was determined. RESULTS: Transfer of Ritonavir at trough concentrations was undetectable ( 20 μg/mL and 25.5 ± 6.9 μg/mL at a concentration of 100 μg/mL. There was no tissue accumulation of Ritonavir either alone or with zidovudine. CONCLUSION: The clearance index of Ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of Ritonavir. (Am J Obstet Gynecol 1998;179:758-61.)
Ludo Lavreys - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics of etravirine combined with atazanavir Ritonavir and a nucleoside reverse transcriptase inhibitor in antiretroviral treatment experienced hiv 1 infected patients
Aids Research and Treatment, 2015Co-Authors: Catherine Orrell, Thomas N Kakuda, Steven Nijs, Lotke Tambuyzer, Andre Nell, Ludo Lavreys, Rodica Van Solingenristea, Franco Felizarta, Frank TomakaAbstract:Objectives. TEACH (NCT00896051) was a randomized, open-label, two-arm Phase II trial to investigate the pharmacokinetic interaction between etravirine and atazanavir/Ritonavir and safety and efficacy in treatment-experienced, HIV-1-infected patients. Methods. After a two-week lead-in of two nucleoside reverse transcriptase inhibitors (NRTIs) and atazanavir/Ritonavir 300/100 mg, 44 patients received etravirine 200 mg bid with one NRTI, plus atazanavir/Ritonavir 300/100 mg or 400/100 mg qd ( each group) over 48 weeks. Results. At steady-state etravirine with atazanavir/Ritonavir 300/100 mg qd or 400/100 mg qd decreased atazanavir by 18% and 9%, respectively, with no change in or versus atazanavir/Ritonavir 300/100 mg qd alone (Day −1). Etravirine was 24% higher and 16% lower with atazanavir/Ritonavir 300/100 or 400/100 mg qd, respectively, versus historical controls. At Week 48, no significant differences were seen between the atazanavir/Ritonavir groups in discontinuations due to adverse events (9.1% each group) and other safety parameters, the proportion of patients with viral load <50 copies/mL (intent-to-treat population, noncompleter = failure) (50.0%, atazanavir/Ritonavir 300/100 mg qd versus 45.5%, 400/100 mg qd), and virologic failures (31.8% versus 27.3%, resp.). Conclusions. Etravirine 200 mg bid can be combined with atazanavir/Ritonavir 300/100 mg qd and an NRTI in HIV-1-infected, treatment-experienced patients without dose adjustment.
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suboptimal adherence to darunavir Ritonavir has minimal effect on efficacy compared with lopinavir Ritonavir in treatment naive hiv infected patients 96 week artemis data
Journal of Antimicrobial Chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
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Suboptimal adherence to darunavir/Ritonavir has minimal effect on efficacy compared with lopinavir/Ritonavir in treatment-naive, HIV-infected patients: 96 week ARTEMIS data
The Journal of antimicrobial chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
Vanitha Sekar - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic interactions of maraviroc with darunavir Ritonavir etravirine and etravirine darunavir Ritonavir in healthy volunteers results of two drug interaction trials
Antimicrobial Agents and Chemotherapy, 2011Co-Authors: Thomas N Kakuda, Monika Schollergyure, Julia Hamlin, Rebecca Mack, Noella Ndongo, Wendy Petit, Caroline E Ridgway, John Davis, Samantha Abel, Vanitha SekarAbstract:The effects of darunavir-Ritonavir at 600 and 100 mg twice daily (b.i.d.) alone, 200 mg of etravirine b.i.d. alone, or 600 and 100 mg of darunavir-Ritonavir b.i.d. with 200 mg etravirine b.i.d. at steady state on the steady-state pharmacokinetics of maraviroc, and vice versa, in healthy volunteers were investigated in two phase I, randomized, two-period crossover studies. Safety and tolerability were also assessed. Coadministration of 150 mg maraviroc b.i.d. with darunavir-Ritonavir increased the area under the plasma concentration-time curve from 0 to 12 h (AUC12) for maraviroc 4.05-fold relative to 150 mg of maraviroc b.i.d. alone. Coadministration of 300 mg maraviroc b.i.d. with etravirine decreased the maraviroc AUC12 by 53% relative to 300 mg maraviroc b.i.d. alone. Coadministration of 150 mg maraviroc b.i.d. with etravirine-darunavir-Ritonavir increased the maraviroc AUC12 3.10-fold relative to 150 mg maraviroc b.i.d. alone. Maraviroc did not significantly affect the pharmacokinetics of etravirine, darunavir, or Ritonavir. Short-term coadministration of maraviroc with darunavir-Ritonavir, etravirine, or both was generally well tolerated, with no safety issues reported in either trial. Maraviroc can be coadministered with darunavir-Ritonavir, etravirine, or etravirine-darunavir-Ritonavir. Maraviroc should be dosed at 600 mg b.i.d. with etravirine in the absence of a potent inhibitor of cytochrome P450 3A (CYP3A) (i.e., a boosted protease inhibitor) or at 150 mg b.i.d. when coadministered with darunavir-Ritonavir with or without etravirine.
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suboptimal adherence to darunavir Ritonavir has minimal effect on efficacy compared with lopinavir Ritonavir in treatment naive hiv infected patients 96 week artemis data
Journal of Antimicrobial Chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
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Suboptimal adherence to darunavir/Ritonavir has minimal effect on efficacy compared with lopinavir/Ritonavir in treatment-naive, HIV-infected patients: 96 week ARTEMIS data
The Journal of antimicrobial chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
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Darunavir/Ritonavir Pharmacokinetics Following Coadministration With Clarithromycin in Healthy Volunteers
Journal of clinical pharmacology, 2008Co-Authors: Vanitha Sekar, Eric Lefebvre, Sabrina Spinosa-guzman, Els De Paepe, Martine De Pauw, Tony Vangeneugden, Richard M. W. HoetelmansAbstract:This study investigated the steady-state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low-dose Ritonavir (darunavir/Ritonavir), and clarithromycin in HIV-negative healthy volunteers. In a 3-way crossover study, 18 individuals received darunavir/Ritonavir 400/100 mg bid, clarithromycin 500 mg bid, and darunavir/Ritonavir 400/100 mg bid plus clarithromycin 500 mg bid in 3 separate sessions for 7 days, with a washout period of at least 7 days between treatments. Pharmacokinetic assessment was performed on day 7. Safety and tolerability of the study medication were monitored throughout. Coadministration of darunavir/Ritonavir with clarithromycin resulted in a reduction in darunavir maximum plasma concentration (Cmax) and area under the curve from administration until 12 hours postdose (AUC12 h) of 17% and 13%, respectively. Ritonavir Cmax and AUC12 h were unchanged. During coadministration with darunavir/Ritonavir, clarithromycin Cmax and AUC12 h increased by 26% and 57%, respectively; 14-hydroxy-clarithromycin plasma concentrations were reduced to below the lower limit of quantification (
Pierremarie Girard - One of the best experts on this subject based on the ideXlab platform.
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suboptimal adherence to darunavir Ritonavir has minimal effect on efficacy compared with lopinavir Ritonavir in treatment naive hiv infected patients 96 week artemis data
Journal of Antimicrobial Chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
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Suboptimal adherence to darunavir/Ritonavir has minimal effect on efficacy compared with lopinavir/Ritonavir in treatment-naive, HIV-infected patients: 96 week ARTEMIS data
The Journal of antimicrobial chemotherapy, 2010Co-Authors: Mark Nelson, Vanitha Sekar, Pierremarie Girard, Ralph Demasi, Liddy Chen, Erik Smets, Ludo LavreysAbstract:Results: Overall adherence was high: 83% of darunavir/Ritonavir-treated patients and 78% of lopinavir/Ritonavirtreated patients were .95% adherent. The difference in virological response rate foradherent versus suboptimally adherent patients was smaller for darunavir/Ritonavir (6% difference: 82% versus 76%, P¼0.3312) than for lopinavir/Ritonavir (25% difference: 78% versus 53%, P,0.0001). In suboptimally adherent patients, a higher virological response rate was seen with darunavir/Ritonavir (76%) versus lopinavir/Ritonavir (53%) (P,0.01). Suboptimally adherent patients (both treatment groups) reported more adverse events (AEs), including gastrointestinal AEs, than adherent patients. Darunavir/Ritonavir had a lower rate of AEs, including gastrointestinal AEs, than lopinavir/ Ritonavir, in adherent and suboptimally adherent patients. Conclusions: Suboptimal adherence had no significant effect on the virological response rate with once-daily darunavir/Ritonavir treatment. In contrast, the lopinavir/Ritonavir response rate was significantly reduced in suboptimally adherent patients compared with adherent patients. Once-daily darunavir/Ritonavir resulted in a higher virological response rate in suboptimally adherent patients compared with lopinavir/Ritonavir.
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Interactions between amprenavir and the lopinavir-Ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus.
Clinical pharmacology and therapeutics, 2004Co-Authors: Anne-marie Taburet, Laurence Morand-joubert, Gilles Raguin, Clotilde Le Tiec, Genevieve Chene, Francois Clavel, Isabelle Vincent, Aurélie Barrail, Cécile Droz, Pierremarie GirardAbstract:Objective This pharmacokinetic study was designed to characterize interactions between amprenavir and the lopinavir-Ritonavir combination in patients infected with human immunodeficiency virus in whom previous antiretroviral therapy had failed. Methods Twenty-seven patients included in a randomized clinical trial (ANRS [National Agency for AIDS Research] Protocol 104) participated in this study. They were randomized to receive Ritonavir at a dose of either 100 mg twice daily or 200 mg twice daily. For the first 2 weeks of therapy, they were randomly assigned to receive lopinavir (400 mg twice daily) and Ritonavir (100 mg twice daily), amprenavir (600 mg twice daily) plus Ritonavir (100 mg twice daily), lopinavir (400 mg twice daily) and Ritonavir (100 mg twice daily) plus additional Ritonavir (100 mg twice daily), or amprenavir (600 mg twice daily) plus Ritonavir (200 mg twice daily). From week 3 onward, all patients received amprenavir plus lopinavir-Ritonavir with or without an additional Ritonavir dose (100 mg twice daily). The pharmacokinetics of the 3 drugs was studied in weeks 2 and 6 of therapy. Results Median amprenavir concentrations decreased by 54% (P = .004) when lopinavir was added to the amprenavir-Ritonavir regimen. Lopinavir weakly displaced amprenavir from plasma proteins: The average unbound fraction of amprenavir was 0.089 in week 2 and 0.114 in week 6 (P = .03), but this did not fully account for the observed interaction. Increasing the Ritonavir dose did not affect the amprenavir concentration. The relationship between lopinavir and Ritonavir concentrations fitted a maximum effect (Emax) model;the average concentration of Ritonavir that yielded a lopinavir concentration of 8119 ng/mL (50% of Emax) was 602 ng/mL (coefficient of variation, 22%). There was a significant relationship between the lopinavir inhibitory quotient and the virologic response in week 2 (P = .005). Conclusion Lopinavir markedly decreases the amprenavir concentration during amprenavir and lopinavir-Ritonavir combination therapy. The inhibitory quotients were more predictive of the short-term virologic response than was the level of drug exposure. Clinical Pharmacology & Therapeutics (2004) 75, 310–323; doi:10.1016/j.clpt.2003.12.013
