38 results on '"Peytavin, G."'
Search Results
2. One-Month Transplacental Pharmacokinetics of Raltegravir in a Premature Newborn after Short-Course Treatment of the HIV-1-Infected Mother
- Author
-
Clavel-Osorio, C., primary, Cazassus, F., additional, Stegmann, S., additional, Huc-Anaïs, P., additional, Lecam, D., additional, and Peytavin, G., additional
- Published
- 2013
- Full Text
- View/download PDF
3. Placental Transfer of Maraviroc in an Ex Vivo Human Cotyledon Perfusion Model and Influence of ABC Transporter Expression
- Author
-
Vinot, C., primary, Gavard, L., additional, Tréluyer, J. M., additional, Manceau, S., additional, Courbon, E., additional, Scherrmann, J. M., additional, Declèves, X., additional, Duro, D., additional, Peytavin, G., additional, Mandelbrot, L., additional, and Giraud, C., additional
- Published
- 2013
- Full Text
- View/download PDF
4. Etravirine Concentrations in the Cervicovaginal Compartment in HIV-1-Infected Women Receiving Etravirine-Containing Antiretroviral Therapy: DIVA 02 Study
- Author
-
Clavel, C., primary, Peytavin, G., additional, Tubiana, R., additional, Soulié, C., additional, Courbon, E., additional, Crenn-Hebert, C., additional, Ichou, H., additional, Blanc, C., additional, Schneider, L., additional, Katlama, C., additional, Marcelin, A.-G., additional, and Mandelbrot, L., additional
- Published
- 2012
- Full Text
- View/download PDF
5. Gag Mutations Can Impact Virological Response to Dual-Boosted Protease Inhibitor Combinations in Antiretroviral-Naïve HIV-Infected Patients
- Author
-
Larrouy, Lucile, primary, Chazallon, C., additional, Landman, R., additional, Capitant, C., additional, Peytavin, G., additional, Collin, G., additional, Charpentier, C., additional, Storto, A., additional, Pialoux, G., additional, Katlama, C., additional, Girard, P. M., additional, Yeni, P., additional, Aboulker, J. P., additional, Brun-Vezinet, F., additional, and Descamps, D., additional
- Published
- 2010
- Full Text
- View/download PDF
6. Activity of Gemifloxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model
- Author
-
Azoulay-Dupuis, E., primary, Bédos, J. P., additional, Mohler, J., additional, Moine, P., additional, Cherbuliez, C., additional, Peytavin, G., additional, Fantin, B., additional, and Köhler, T., additional
- Published
- 2005
- Full Text
- View/download PDF
7. Polymorphism of the Human Immunodeficiency Virus Type 2 (HIV-2) Protease Gene and Selection of Drug Resistance Mutations in HIV-2-Infected Patients Treated with Protease Inhibitors
- Author
-
Damond, F., primary, Brun-Vezinet, F., additional, Matheron, S., additional, Peytavin, G., additional, Campa, P., additional, Pueyo, S., additional, Mammano, F., additional, Lastere, S., additional, Farfara, I., additional, Simon, F., additional, Chene, G., additional, and Descamps, D., additional
- Published
- 2005
- Full Text
- View/download PDF
8. Activities of Garenoxacin against Quinolone-Resistant Streptococcus pneumoniae Strains In Vitro and in a Mouse Pneumonia Model
- Author
-
Azoulay-Dupuis, E., primary, Bédos, J. P., additional, Mohler, J., additional, Peytavin, G., additional, Isturiz, R., additional, Moine, P., additional, Rieux, V., additional, Cherbuliez, C., additional, Péchère, J. C., additional, Fantin, B., additional, and Köhler, T., additional
- Published
- 2004
- Full Text
- View/download PDF
9. Reply to Yan and Muller, "Captisol and GS-704277, but Not GS-441524, Are Credible Mediators of Remdesivir's Nephrotoxicity".
- Author
-
Lê MP, Le Beller C, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, and Peytavin G
- Subjects
- Adenosine analogs & derivatives, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Furans, Humans, Neuroglia, Pandemics, Pyrroles, SARS-CoV-2, Transplant Recipients, Triazines, beta-Cyclodextrins, COVID-19, Lung Transplantation, Renal Dialysis
- Published
- 2020
- Full Text
- View/download PDF
10. Removal of Remdesivir's Metabolite GS-441524 by Hemodialysis in a Double Lung Transplant Recipient with COVID-19.
- Author
-
Lê MP, Le Hingrat Q, Jaquet P, Wicky PH, Bunel V, Massias L, Visseaux B, Messika J, Descamps D, Mal H, Timsit JF, and Peytavin G
- Subjects
- Adenosine analogs & derivatives, Adenosine Monophosphate administration & dosage, Adenosine Monophosphate adverse effects, Adenosine Monophosphate chemistry, Adenosine Monophosphate metabolism, Alanine administration & dosage, Alanine adverse effects, Alanine chemistry, Alanine metabolism, Antiviral Agents adverse effects, Antiviral Agents chemistry, Antiviral Agents metabolism, COVID-19, Coronavirus Infections drug therapy, Coronavirus Infections surgery, Coronavirus Infections virology, Drug Interactions, Furans adverse effects, Furans chemistry, Humans, Intensive Care Units, Lung Transplantation, Multiple Organ Failure, Pandemics, Pneumonia, Viral surgery, Pneumonia, Viral virology, Pyrroles adverse effects, Pyrroles chemistry, Renal Dialysis, SARS-CoV-2, Transplant Recipients, Triazines adverse effects, Triazines chemistry, beta-Cyclodextrins adverse effects, beta-Cyclodextrins chemistry, COVID-19 Drug Treatment, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents administration & dosage, Betacoronavirus drug effects, Coronavirus Infections therapy, Furans urine, Pneumonia, Viral therapy, Pyrroles urine, Triazines urine, beta-Cyclodextrins urine
- Abstract
Remdesivir has reported efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and in vivo Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In intensive care unit (ICU) settings, in which multiple-organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and sulfobutylether β-cyclodextrin sodium (SEBCD). Additional studies may prove informative, particularly in the evaluations of therapeutic options for coronavirus disease 2019 (COVID-19)., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
- Full Text
- View/download PDF
11. Screening for Human Immunodeficiency Virus Infection by Use of a Fourth-Generation Antigen/Antibody Assay and Dried Blood Spots: In-Depth Analysis of Sensitivity and Performance Assessment in a Cross-Sectional Study.
- Author
-
Stefic K, Guinard J, Peytavin G, Saboni L, Sommen C, Sauvage C, Lot F, Laperche S, Velter A, and Barin F
- Subjects
- Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Cross-Sectional Studies, HIV Antibodies immunology, HIV Antigens immunology, HIV Infections drug therapy, HIV Infections immunology, Humans, Reproducibility of Results, Sensitivity and Specificity, Seroconversion, Dried Blood Spot Testing methods, Dried Blood Spot Testing standards, HIV drug effects, HIV immunology, HIV Infections diagnosis, HIV Infections virology, Immunoassay methods, Immunoassay standards
- Abstract
We evaluated the performance of a fourth-generation antigen/antibody (Ag/Ab) assay for detecting HIV-1 infection on dried blood spots (DBS) both in a conventional laboratory environment and in an epidemiological survey corresponding to a real-life situation. Although a 2-log loss of sensitivity compared to that with plasma was observed when using DBS in an analytical analysis, the median delay of positivity between DBS and crude serum during the early phase postacute infection was 7 days. The performance of the fourth-generation assay on DBS was approximately similar to that of a third-generation (antibody only) assay using crude serum samples. Among 2,646 participants of a cross-sectional study in a population of men having sex with men, 428 DBS were found reactive, but negative results were obtained from 5 DBS collected from individuals who self-reported a positive HIV status, confirmed by detection of antiretroviral (ARV) drugs in their DBS. The data generated allowed us to estimate a sensitivity of 98.8% of the fourth-generation assay/DBS strategy in a high-risk population, even including a broad majority of individuals on ARV treatment among those HIV positive. Our study brings additional proofs that DBS testing using a fourth-generation immunoassay is a reliable strategy able to provide alternative approaches for both individual HIV testing and surveillance of various populations., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
- Full Text
- View/download PDF
12. Bidirectional Transfer of Raltegravir in an Ex Vivo Human Cotyledon Perfusion Model.
- Author
-
Vinot C, Tréluyer JM, Giraud C, Gavard L, Peytavin G, and Mandelbrot L
- Subjects
- Female, Gestational Age, Humans, Maternal-Fetal Exchange physiology, Pregnancy, Fetus metabolism, HIV Integrase Inhibitors metabolism, Placenta metabolism, Raltegravir Potassium metabolism
- Abstract
Placental transfer of the HIV integrase inhibitor raltegravir (RLT) was investigated in term human cotyledons in the maternal-to-fetal (n = 3) and fetal-to-maternal (n = 6) directions. In the maternal-to-fetal direction, the mean ± standard deviation (SD) fetal transfer rate (FTR) was 9.1% ± 1.4%, and the mean ± SD clearance index (IC), i.e., RLT FTR/antipyrine FTR, was 0.28 ± 0.05. In the fetal-to-maternal direction, the mean ± SD CI was 0.31 ± 0.09. Placental transfer of RLT was high in both directions., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
- Full Text
- View/download PDF
13. Erratum for Mandelbrot et al., placental transfer of rilpivirine in an ex vivo human cotyledon perfusion model.
- Author
-
Mandelbrot L, Duro D, Belissa E, and Peytavin G
- Published
- 2015
- Full Text
- View/download PDF
14. Placental transfer of rilpivirine in an ex vivo human cotyledon perfusion model.
- Author
-
Mandelbrot L, Duro D, Belissa E, and Peytavin G
- Subjects
- Female, Humans, Maternal-Fetal Exchange, Pregnancy, Placenta metabolism, Reverse Transcriptase Inhibitors metabolism, Rilpivirine metabolism
- Abstract
Placental transfers of the HIV nonnucleoside reverse transcriptase inhibitor rilpivirine were investigated in 8 term human cotyledons perfused with rilpivirine (400 ng/ml) in the maternal-to-fetal direction. The mean fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 15 to 90 min) was 26% ± 8% (mean ± standard deviation), and the clearance index (rilpivirine FTR/antipyrine FTR) was 61% ± 20%. This shows that rilpivirine crosses the placenta at a relatively high rate, suggesting that the fetus is exposed to the compound during treatment of the mother., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
- View/download PDF
15. Placental transfer of darunavir in an ex vivo human cotyledon perfusion model.
- Author
-
Mandelbrot L, Duro D, Belissa E, and Peytavin G
- Subjects
- Biological Transport, Darunavir, Female, HIV Protease Inhibitors therapeutic use, Humans, Pregnancy, Sulfonamides therapeutic use, HIV Protease Inhibitors metabolism, Maternal-Fetal Exchange, Placenta metabolism, Sulfonamides metabolism
- Abstract
Placental transfer of the HIV protease inhibitor darunavir was investigated in 5 term human cotyledons perfused with darunavir (1,000 ng/ml) in the maternal to fetal direction. The mean (± the standard deviation [SD]) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 15.0%±2.1%, and the mean (±SD) clearance index (darunavir FTR/antipyrine FTR) was 40.3%±5.8%. This shows that darunavir crosses the placenta at a relatively low rate, resulting in fetal exposure., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
- View/download PDF
16. Using pharmacokinetic and viral kinetic modeling to estimate the antiviral effectiveness of telaprevir, boceprevir, and pegylated interferon during triple therapy in treatment-experienced hepatitis C virus-infected cirrhotic patients.
- Author
-
Laouénan C, Marcellin P, Lapalus M, Khelifa-Mouri F, Boyer N, Zoulim F, Serfaty L, Bronowicki JP, Martinot-Peignoux M, Lada O, Asselah T, Dorival C, Hézode C, Carrat F, Nicot F, Peytavin G, Mentré F, and Guedj J
- Subjects
- Adult, Antiviral Agents pharmacokinetics, Antiviral Agents pharmacology, Drug Therapy, Combination, Female, Humans, Interferon-alpha administration & dosage, Interferon-alpha pharmacokinetics, Interferon-alpha pharmacology, Kinetics, Male, Middle Aged, Models, Biological, Oligopeptides administration & dosage, Oligopeptides pharmacokinetics, Oligopeptides pharmacology, Polyethylene Glycols administration & dosage, Polyethylene Glycols pharmacokinetics, Polyethylene Glycols pharmacology, Proline administration & dosage, Proline pharmacokinetics, Proline pharmacology, Proline therapeutic use, Recombinant Proteins administration & dosage, Recombinant Proteins pharmacokinetics, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use, Treatment Outcome, Antiviral Agents therapeutic use, Hepacivirus drug effects, Hepatitis C drug therapy, Interferon-alpha therapeutic use, Oligopeptides therapeutic use, Polyethylene Glycols therapeutic use, Proline analogs & derivatives
- Abstract
Triple therapy combining a protease inhibitor (PI) (telaprevir or boceprevir), pegylated interferon (PEG-IFN), and ribavirin (RBV) has dramatically increased the chance of eradicating hepatitis C virus (HCV). However, the efficacy of this treatment remains suboptimal in cirrhotic treatment-experienced patients. Here, we aimed to better understand the origin of this impaired response by estimating the antiviral effectiveness of each drug. Fifteen HCV genotype 1-infected patients with compensated cirrhosis, who were nonresponders to prior PEG-IFN/RBV therapy, were enrolled in a nonrandomized study. HCV RNA and concentrations of PIs, PEG-IFN, and RBV were frequently assessed in the first 12 weeks of treatment and were analyzed using a pharmacokinetic/viral kinetic model. The two PIs achieved similar levels of molar concentrations (P=0.5), but there was a significant difference in the 50% effective concentrations (EC50) (P=0.008), leading to greater effectiveness for telaprevir than for boceprevir in blocking viral production (99.8% versus 99.0%, respectively, P=0.002). In all patients, the antiviral effectiveness of PEG-IFN was modest (43.4%), and there was no significant contribution of RBV exposure to the total antiviral effectiveness. The second phase of viral decline, which is attributed to the loss rate of infected cells, was slow (0.19 day(-1)) and was higher in patients who subsequently eradicated HCV (P=0.03). The two PIs achieved high levels of antiviral effectiveness. However, the suboptimal antiviral effectiveness of PEG-IFN/RBV and the low loss of infected cells suggest that a longer treatment duration might be needed in cirrhotic treatment-experienced patients and that a future IFN-free regimen may be particularly beneficial in these patients., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
- Full Text
- View/download PDF
17. In vitro phenotypic susceptibility of HIV-2 clinical isolates to CCR5 inhibitors.
- Author
-
Visseaux B, Charpentier C, Hurtado-Nedelec M, Storto A, Antoine R, Peytavin G, Damond F, Matheron S, Brun-Vézinet F, and Descamps D
- Subjects
- Cells, Cultured, Female, Genotype, HIV Infections metabolism, HIV Infections virology, HIV-1 metabolism, HIV-2 metabolism, Humans, Inhibitory Concentration 50, Leukocytes, Mononuclear, Lymphocyte Activation drug effects, Male, Maraviroc, Models, Biological, Phytohemagglutinins pharmacology, Receptors, CCR5 metabolism, Receptors, CXCR4 antagonists & inhibitors, Receptors, CXCR4 metabolism, Species Specificity, Virus Replication drug effects, Anti-HIV Agents pharmacology, CCR5 Receptor Antagonists, Cyclohexanes pharmacology, Drug Resistance, Viral, HIV Infections drug therapy, HIV-1 drug effects, HIV-2 drug effects, Triazoles pharmacology
- Abstract
HIV-2 is naturally resistant to nonnucleoside reverse transcriptase inhibitors, to a fusion inhibitor, and to some of the protease inhibitors. Maraviroc is the first drug of the new anti-CCR5 drug class and is effective only on CCR5-tropic (R5) HIV-1. No previous studies concerning HIV-2 susceptibility to maraviroc have been reported yet. We developed a phenotypic maraviroc susceptibility test using a peripheral blood mononuclear cell (PBMC) model. We analyzed the maraviroc susceptibility of 13 R5 HIV-2, 2 X4R5 (dual) HIV-2, and 2 CXCR4-tropic (X4) HIV-2 clinical isolates. We also tested, with the same protocol, 1 X4 HIV-1 and 4 R5 HIV-1 clinical isolates. For the R5 HIV-2 clinical isolates, the 50% effective concentration (EC(50)) for maraviroc was 0.80 nM (interquartile range [IQR], 0.48 to 1.39 nM), similar to that observed for the R5 HIV-1 isolates. The median maximum percentage of inhibition in the R5 HIV-2 isolates was 93% (IQR, 84 to 98%), similar to that observed in the R5 HIV-1 isolates. As expected, both X4 HIV-1 and HIV-2 were highly resistant to maraviroc. Our study showed for the first time that maraviroc is active in vitro against R5 HIV-2. The new tools we developed will allow identification of HIV-2-infected patients eligible for CCR5 inhibitor use and management of virological failure when receiving a maraviroc-based regimen.
- Published
- 2012
- Full Text
- View/download PDF
18. Raltegravir concentrations in the genital tract of HIV-1-infected women treated with a raltegravir-containing regimen (DIVA 01 study).
- Author
-
Clavel C, Peytavin G, Tubiana R, Soulié C, Crenn-Hebert C, Heard I, Bissuel F, Ichou H, Ferreira C, Katlama C, Marcelin AG, and Mandelbrot L
- Subjects
- Adult, Female, Humans, Middle Aged, Raltegravir Potassium, Acquired Immunodeficiency Syndrome drug therapy, Anti-HIV Agents pharmacokinetics, Cervix Uteri metabolism, HIV-1, Pyrrolidinones pharmacokinetics, Vagina metabolism
- Abstract
We studied the penetration of raltegravir and HIV shedding in the genital tract among 14 HIV-1-infected women receiving a raltegravir-containing regimen who had <40 copies/ml blood plasma (BP) HIV RNA. None of the cervicovaginal fluid (CVF) samples showed detectable HIV RNA. Median raltegravir concentrations were 235 ng/ml in BP and 93 ng/ml in CVF, with a CVF/BP ratio of approximately 2.3. This good penetration of raltegravir may contribute to the control of viral replication in the female genital tract.
- Published
- 2011
- Full Text
- View/download PDF
19. Low frequency of intermittent HIV-1 semen excretion in patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy.
- Author
-
Lambert-Niclot S, Peytavin G, Duvivier C, Poirot C, Algarte-Genin M, Pakianather S, Meynard JL, Valantin MA, Molina JM, Flandre P, Katlama C, Calvez V, and Marcelin AG
- Subjects
- Darunavir, Drug Administration Schedule, HIV Infections blood, HIV Infections drug therapy, HIV Infections metabolism, HIV-1 drug effects, HIV-1 pathogenicity, Humans, Male, Plasma chemistry, RNA, Viral genetics, Reverse Transcriptase Inhibitors blood, Reverse Transcriptase Inhibitors metabolism, Ritonavir blood, Ritonavir metabolism, Semen chemistry, Sulfonamides blood, Sulfonamides metabolism, Reverse Transcriptase Inhibitors therapeutic use, Ritonavir therapeutic use, Sulfonamides therapeutic use
- Abstract
HIV-1 RNA level and darunavir concentration in the genital tract were measured in 45 men receiving darunavir-ritonavir mono- or tritherapy. At week 48, a low frequency (3/45) of HIV-1 RNA shedding was observed in patients (1 on monotherapy and 2 on triple therapy), although they had undetectable HIV-1 RNA in plasma. The median darunavir seminal plasma concentration was close to the blood plasma free fraction, demonstrating a good penetration of darunavir into the male genital tract.
- Published
- 2010
- Full Text
- View/download PDF
20. Clinical and resistance consequences of misquantification of plasma and cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) RNA in samples from an HIV-1 subtype G-infected patient.
- Author
-
Delaugerre C, Denis B, Peytavin G, Palmer P, Mourez T, Le Goff J, Molina JM, and Simon F
- Subjects
- Adult, Diagnostic Errors, Encephalitis, Viral, Female, Humans, RNA, Viral blood, RNA, Viral cerebrospinal fluid, Anti-HIV Agents therapeutic use, Cerebrospinal Fluid virology, Drug Resistance, Viral, HIV Infections virology, HIV-1 isolation & purification, Plasma virology, Viral Load
- Abstract
Human immunodeficiency virus (HIV) load is the main marker used to monitor antiviral treatment efficacy and resistance. We report a case of underquantification of HIV type 1 (HIV-1) RNA in plasma and cerebrospinal fluid from an HIV-1 subtype G-infected woman, leading to delayed diagnosis of HIV encephalitis and to the emergence of drug resistance.
- Published
- 2009
- Full Text
- View/download PDF
21. Tipranavir-ritonavir genotypic resistance score in protease inhibitor-experienced patients.
- Author
-
Marcelin AG, Masquelier B, Descamps D, Izopet J, Charpentier C, Alloui C, Bouvier-Alias M, Signori-Schmuck A, Montes B, Chaix ML, Amiel C, Santos GD, Ruffault A, Barin F, Peytavin G, Lavignon M, Flandre P, and Calvez V
- Subjects
- Anti-HIV Agents therapeutic use, Drug Therapy, Combination, Female, Genotype, HIV Infections virology, HIV Protease drug effects, HIV Protease Inhibitors therapeutic use, HIV-1 classification, HIV-1 enzymology, HIV-1 genetics, Humans, Male, Mutation, Reverse Transcriptase Inhibitors therapeutic use, Sulfonamides, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Protease genetics, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, Pyridines pharmacology, Pyrones pharmacology, Ritonavir pharmacology
- Abstract
To identify mutations associated with the virological response (VR) to a tipranavir-ritonavir (TPV/r)-based regimen, 143 patients previously treated with protease inhibitor (PI) were studied. VR was defined by a decrease of at least 1 log(10) in, or undetectable, human immunodeficiency virus (HIV) RNA at month 3. The effect of each mutation in the protease, considering all variants at a residue as a single variable, on the VR to TPV/r was investigated. Mutations at six residues were associated with a lower VR (E35D/G/K/N, M36I/L/V, Q58E, Q61D/E/G/H/N/R, H69I/K/N/Q/R/Y, and L89I/M/R/T/V), and one mutation was associated with a higher VR (F53L/W/Y). The genotypic score M36I/L/V-53L/W/Y + Q58E + H69I/K/N/Q/R/Y + L89I/M/R/T/V was selected as providing a strong association with VR. For the seven patients with a genotypic score of -1 (viruses with only mutation at codon 53), the percentage of responders was 100% and the percentages were 79%, 56%, 33%, 21%, and 0% for those with scores of 0, 1, 2, 3, and 4, respectively. The percentage of patients showing a response to TPV/r was lower for patients infected with non-clade B viruses (n = 16, all non-B subtypes considered together) than for those infected with clade B viruses (n = 127) (25% and 59%, respectively; P = 0.015). Most mutations associated with VR to TPV/r had not previously been associated with PI resistance. This is consistent with phenotypic analysis showing that TPV has a unique resistance profile. Mutations at five positions (35, 36, 61, 69, and 89) were observed significantly more frequently in patients infected with a non-B subtype than in those infected with the B subtype, probably explaining the lower VR observed in these patients.
- Published
- 2008
- Full Text
- View/download PDF
22. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro.
- Author
-
Malet I, Delelis O, Valantin MA, Montes B, Soulie C, Wirden M, Tchertanov L, Peytavin G, Reynes J, Mouscadet JF, Katlama C, Calvez V, and Marcelin AG
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, HIV Infections virology, HIV Integrase chemistry, HIV Integrase genetics, HIV Integrase Inhibitors pharmacology, HIV-1 enzymology, Humans, Microbial Sensitivity Tests, Organic Chemicals pharmacology, Pyrrolidinones, Raltegravir Potassium, Treatment Failure, Viral Load, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Integrase drug effects, HIV Integrase Inhibitors therapeutic use, HIV-1 drug effects, Mutation, Organic Chemicals therapeutic use
- Abstract
Raltegravir (MK-0518) is a potent inhibitor of human immunodeficiency virus (HIV) integrase and is clinically effective against viruses resistant to other classes of antiretroviral agents. However, it can select mutations in the HIV integrase gene. Nine heavily pretreated patients who received salvage therapy including raltegravir and who subsequently developed virological failure under raltegravir therapy were studied. For each patient, the sequences of the integrase-coding region were determined and compared to that at the beginning of the treatment. Four different mutation profiles were identified in these nine patients: E92Q, G140S Q148H, N155H, and E157Q mutations. For four patients, each harboring a different profile, the wild-type and mutated integrases were produced, purified, and assayed in vitro. All the mutations identified altered the activities of integrase protein: both 3' processing and strand transfer activities were moderately affected in the E92Q mutant; strand transfer was markedly impaired in the N155H mutant; both activities were strongly impaired in the G140S Q148H mutant; and the E157Q mutant was almost completely inactive. The sensitivities of wild-type and mutant integrases to raltegravir were compared. The E92Q and G140S Q148H profiles were each associated with a 7- to 8-fold decrease in sensitivity, and the N155H mutant was more than 14-fold less sensitive to raltegravir. At least four genetic profiles (E92Q, G140S Q148H, N155H, and E157Q) can be associated with in vivo treatment failure and resistance to raltegravir. These mutations led to strong impairment of enzymes in vitro in the absence of raltegravir: strand transfer activity was affected, and in some cases 3' processing was also impaired.
- Published
- 2008
- Full Text
- View/download PDF
23. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors.
- Author
-
Desbois D, Roquebert B, Peytavin G, Damond F, Collin G, Bénard A, Campa P, Matheron S, Chêne G, Brun-Vézinet F, and Descamps D
- Subjects
- Darunavir, HIV Protease drug effects, HIV-2 enzymology, Humans, Inhibitory Concentration 50, Lopinavir, Microbial Sensitivity Tests, Phenotype, Pyrimidinones pharmacology, Saquinavir pharmacology, Sulfonamides pharmacology, HIV Protease Inhibitors pharmacology, HIV-2 classification, HIV-2 drug effects
- Abstract
We determine phenotypic susceptibility of human immunodeficiency virus type 2 (HIV-2) isolates to amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, saquinavir, and tipranavir. Saquinavir, lopinavir, and darunavir are potent against wild-type HIV-2 isolates and should be preferred as first-line options for HIV-2-infected patients. Other protease inhibitors are less active against HIV-2 than against HIV-1.
- Published
- 2008
- Full Text
- View/download PDF
24. Antiretroviral therapy with a twice-daily regimen containing 400 milligrams of indinavir and 100 milligrams of ritonavir in human immunodeficiency virus type 1-infected women during pregnancy.
- Author
-
Ghosn J, De Montgolfier I, Cornélie C, Dominguez S, Pérot C, Peytavin G, Marcelin AG, Pauchard M, Ouagari Z, Bonmarchand M, Agher R, Calvez V, Bricaire F, Dommergues M, Katlama C, and Tubiana R
- Subjects
- Adult, Anti-HIV Agents administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Female, HIV Infections transmission, HIV Infections virology, HIV-1 drug effects, Humans, Indinavir administration & dosage, Infant, Newborn, Pregnancy, Pregnancy Complications, Infectious virology, Pregnancy Outcome, Reverse Transcriptase Inhibitors administration & dosage, Ritonavir administration & dosage, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Indinavir therapeutic use, Infectious Disease Transmission, Vertical prevention & control, Pregnancy Complications, Infectious drug therapy, Reverse Transcriptase Inhibitors therapeutic use, Ritonavir therapeutic use
- Abstract
We evaluated the safety and efficacy of a twice daily regimen containing 400 mg of indinavir and 100 mg of ritonavir in 32 human immunodeficiency virus (HIV)-infected women during pregnancy. The median indinavir trough concentration was 208 ng/ml during the third trimester. At delivery, 26 of 28 women on indinavir-ritonavir had HIV RNA levels of <200 copies/ml. No infant was HIV infected. These data are encouraging for the use of this combination for prevention of mother-to-child transmission of HIV.
- Published
- 2008
- Full Text
- View/download PDF
25. Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir.
- Author
-
Lambert-Niclot S, Flandre P, Canestri A, Peytavin G, Blanc C, Agher R, Soulié C, Wirden M, Katlama C, Calvez V, and Marcelin AG
- Subjects
- Darunavir, Drug Therapy, Combination, Female, HIV Infections virology, HIV Protease drug effects, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, HIV-1 enzymology, HIV-1 genetics, Humans, Male, Microbial Sensitivity Tests methods, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Risk Factors, Selection, Genetic, Sulfonamides pharmacology, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Protease genetics, HIV Protease Inhibitors therapeutic use, Mutation, Sulfonamides therapeutic use, Treatment Failure
- Abstract
The objective of this study was to characterize the mutations selected by darunavir (DRV) use in protease inhibitor (PI)-experienced patients and the associated factors. We analyzed treatment failure in 54 PI-experienced human immunodeficiency virus (HIV)-infected patients on a DRV- and ritonavir-containing regimen. Viral genotyping was carried out at the baseline, at between 1 and 3 months of treatment, and at between 3 and 6 months of treatment to search for the selection of mutations conferring resistance to PIs. The median baseline HIV RNA level was 4.9 log(10) copies/ml, and the median CD4 count was 87 cells/mm(3). At the baseline, the median numbers of resistance mutations were as follows: 3 DRV resistance mutations, 4 major PI resistance mutations, and 10 minor PI resistance mutations. The most common mutations that emerged at rebound included V32I (44%), I54M/L (24%), L33F (25%), I84V (21%), and L89V (12%). Multivariate analysis showed that higher baseline HIV RNA levels and smaller numbers of nucleoside reverse transcriptase inhibitor simultaneously used with DRV were associated with a higher risk of DRV resistance mutation selection. By contrast, L76V, a known DRV resistance mutation, was found to decrease the risk of selection of another DRV resistance mutation. The occurrence of virological failure while a patient was on DRV was associated with the selection of mutations that increased the level of DRV resistance without affecting susceptibility to tipranavir (TPV). In these PI-treated patients who displayed treatment failure while they were on a DRV-containing regimen, we confirmed the set of emerging mutations associated with DRV failure and identified the factors associated with the selection of these mutations. TPV susceptibility does not seem to be affected by the selection of a DRV resistance mutation.
- Published
- 2008
- Full Text
- View/download PDF
26. Impact of nevirapine (NVP) plasma concentration on selection of resistant virus in mothers who received single-dose NVP to prevent perinatal human immunodeficiency virus type 1 transmission and persistence of resistant virus in their infected children.
- Author
-
Chaix ML, Ekouevi DK, Peytavin G, Rouet F, Tonwe-Gold B, Viho I, Bequet L, Amani-Bosse C, Menan H, Leroy V, Rouzioux C, and Dabis F
- Subjects
- Adult, Anti-HIV Agents pharmacokinetics, Cohort Studies, Drug Resistance, Viral genetics, Female, HIV Infections transmission, HIV-1 genetics, Humans, Infant, Newborn, Monocytes virology, Mutation genetics, Nevirapine pharmacokinetics, Phylogeny, Predictive Value of Tests, Pregnancy, RNA, Viral blood, Anti-HIV Agents blood, Anti-HIV Agents pharmacology, Drug Resistance, Viral drug effects, HIV Infections prevention & control, HIV Infections virology, HIV-1 drug effects, Nevirapine blood, Nevirapine pharmacology
- Abstract
Nonnucleoside reverse transcriptase inhibitor resistance following the use of single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in Abidjan, Côte d'Ivoire, a short-course regimen of zidovudine was associated with sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and its relationship with NVP concentration in mothers. Genotypic resistance analysis was performed on mothers' plasma samples at week 4 postpartum (PP) and on human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC) when an NVP resistance mutation was detected. The same tests were performed for the infected children at week 4, month 3, and month 12. Mothers' NVP plasma concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851 ng/ml for the mothers harboring NVP-R virus (P = 0.014). NVP-R mutations were detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in 6 of 26 infected children at week 4. All 6 children had detectable NVP-R mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month 12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells. Emergence of NVP-R virus in mothers is strongly correlated with a high level of plasma NVP concentration, owing to a prolonged postpartum period of viral replication under NVP selective pressure. The follow-up of the cohort demonstrates the prolonged archive of resistant virus.
- Published
- 2007
- Full Text
- View/download PDF
27. Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021).
- Author
-
Delaunay C, Brun-Vézinet F, Landman R, Collin G, Peytavin G, Trylesinski A, Flandre P, Miller M, and Descamps D
- Subjects
- Adenine administration & dosage, Dideoxynucleosides administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Humans, Lamivudine administration & dosage, Mutation, Organophosphonates administration & dosage, Pilot Projects, RNA, Viral genetics, RNA-Directed DNA Polymerase genetics, Reverse Transcriptase Inhibitors administration & dosage, Sequence Analysis, Protein, Tenofovir, Treatment Failure, Viral Load, Adenine analogs & derivatives, Adenine therapeutic use, Dideoxynucleosides therapeutic use, HIV Infections drug therapy, HIV-1 genetics, Lamivudine therapeutic use, Organophosphonates therapeutic use, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Tonus was a pilot study in which previously untreated human immunodeficiency virus type 1 (HIV-1)-infected patients received the combination of abacavir, lamivudine, and tenofovir once a day. There was a high rate of early virological failure, and the M184V and K65R mutations were frequently detected at week 12 (W12). The objective of this study was to examine the selection dynamics of the K65R and M184V/I mutations. Bulk sequencing of the reverse transcriptase (RT) gene was performed on plasma HIV-1 RNA at baseline, W4, and W12 for 21 patients with detectable viral loads. The RT genes from baseline, W4, and W12 plasma samples from five patients who developed both M184V and K65R but with different mutational patterns were also cloned and screened for the K65R mutation by selective real-time PCR. At baseline, bulk sequencing and clonal analysis showed only wild-type RT sequences. At W4, M184V/I was detected in 12/19 patients and K65K/R in 2 patients by bulk sequencing. At W12, M184V/I was found in 18/20 patient, together with the K65R in 13 patients. At W4, clonal analysis revealed the K65R mutation in 0.6 to 48% of clones in the five patients studied. At W12, the K65R mutation was found in 30 to 100% of clones. K65R and M184V/I seemed to arise in separate clones, followed by an enrichment of viruses containing both mutations. The clinical relevance of this independent evolution is unclear. M184V/I was selected more frequently than K65R at W4. However, K65R was also detected early using a clone-sensitive genotyping method. All three nucleoside analogs are known to select the K65R and/or M184V/I mutation. This convergent genetic pathway to resistance, associated with lower antiretroviral potency, may explain the high selection rate of these mutations in this trial.
- Published
- 2005
- Full Text
- View/download PDF
28. Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients.
- Author
-
Marcelin AG, Cohen-Codar I, King MS, Colson P, Guillevic E, Descamps D, Lamotte C, Schneider V, Ritter J, Segondy M, Peigue-Lafeuille H, Morand-Joubert L, Schmuck A, Ruffault A, Palmer P, Chaix ML, Mackiewicz V, Brodard V, Izopet J, Cottalorda J, Kohli E, Chauvin JP, Kempf DJ, Peytavin G, and Calvez V
- Subjects
- Adult, Aged, Drug Combinations, Drug Monitoring, Female, Genotype, HIV-1 genetics, Humans, Linear Models, Lopinavir, Male, Middle Aged, Mutation genetics, Predictive Value of Tests, RNA, Viral genetics, HIV Infections drug therapy, HIV Infections virology, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, Pyrimidinones therapeutic use, Ritonavir therapeutic use
- Abstract
The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.
- Published
- 2005
- Full Text
- View/download PDF
29. Clinically relevant interpretation of genotype and relationship to plasma drug concentrations for resistance to saquinavir-ritonavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients.
- Author
-
Marcelin AG, Dalban C, Peytavin G, Lamotte C, Agher R, Delaugerre C, Wirden M, Conan F, Dantin S, Katlama C, Costagliola D, and Calvez V
- Subjects
- Codon genetics, Drug Combinations, Drug Resistance, Viral, Genotype, HIV Protease Inhibitors blood, HIV-1 enzymology, Humans, Mutation, RNA, Viral analysis, RNA, Viral genetics, Saquinavir blood, HIV Protease genetics, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors pharmacology, HIV-1 genetics, Ritonavir pharmacology, Saquinavir pharmacokinetics, Saquinavir pharmacology
- Abstract
It has been shown that virological protease inhibitor (PI) resistance mutations present at the initiation of saquinavir (SQV) plus ritonavir (RTV) therapy in PI-experienced patients are the strongest predictors of virological response. But most of the current resistance algorithms are adapted for unboosted SQV regimens. We applied a stepwise methodology for the development and validation of a clinically relevant genotypic resistance score for an SQV (800 mg twice per day [b.i.d.]) plus RTV (100 mg b.i.d.)-containing regimen. PI-experienced patients treated by this regimen achieved a human immunodeficiency virus plasma viral load (VL) of <200 copies/ml at months 3 to 5 for 41.7% of subjects. Adjusted in a multivariate analysis, taking into account all the confounding factors, such as the nucleoside used, five mutations were combined in a resistance score associated with a reduced virological response to an SQV-plus-RTV regimen: L24I, I62V, V82A/F/T/S, I84V, and L90IM. Patients with isolates harboring 0 to 1 mutation among the score achieved -2.20 log10 and -1.23 log10 copies/ml of VL reduction, respectively, while it was -0.27 log10 copies/ml for those with at least two mutations, classifying the isolates as "no evidence of resistance" (0 or 1 mutation) or "resistance " (> or =2 mutations). The minimum concentration in plasma (Cmin) of SQV alone was not associated with the virological response. However, the combination of the SQV Cmin and the genotypic score, expressed as the genotypic inhibitory quotient, was predictive of the virological response, suggesting that the interpretation of SQV concentrations in plasma should be done only in the context of the resistance index provided by viral genotype for PI-experienced patients.
- Published
- 2004
- Full Text
- View/download PDF
30. Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs.
- Author
-
Joly V, Descamps D, Peytavin G, Touati F, Mentre F, Duval X, Delarue S, Yeni P, and Brun-Vezinet F
- Subjects
- Drug Resistance, Viral, Follow-Up Studies, Genotype, HIV Infections genetics, Humans, Mutation, RNA, Viral biosynthesis, RNA, Viral genetics, Antiretroviral Therapy, Highly Active, HIV Infections virology, HIV-1 drug effects, Reverse Transcriptase Inhibitors pharmacology
- Abstract
We studied the evolution of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations among 29 human immunodeficiency virus type 1 (HIV-1)-infected patients who experienced virologic failure when receiving an NNRTI-containing regimen (nevirapine, delavirdine, or efavirenz) and subsequently switched to antiretroviral therapy without NNRTIs. Genotypic resistance was determined from plasma samples collected at the time of NNRTI withdrawal (baseline) and during follow-up. At baseline, 83% of patients had more than two thymidine analog resistance mutations (TAMs), and all had NNRTI resistance mutations. Mutations at codons 103, 181, and 190 were found in 62, 62, and 34% of the patients, respectively. Follow-up samples were available after a median time of 6 months in all patients and at 12 months in 22 patients. The mean number of resistance mutations to NNRTIs was significantly lower at months 6 (1.34 +/- 1.04) and 12 (1.18 +/- 1.05) than at month 0 (2.03 +/- 1.02) (P < 0.009). The percentages of patients with at least one NNRTI resistance mutation were 100, 76, and 73% at baseline, month 6, and month 12, respectively (P < 0.0044). Overall, 70% of the patients had a mutation at codon 103 or 181 at month 12. The mean number of TAMs did not vary significantly during follow-up. Our data show that, in the context of maintained antiretroviral therapy, NNRTI resistance mutations persist in two-thirds of the patients in spite of NNRTI withdrawal. These results argue for the low impact of NNRTI resistance mutations on viral fitness and suggest that resistance mutations to different classes of drugs are associated on the same genome, at least in some of the resistant strains.
- Published
- 2004
- Full Text
- View/download PDF
31. Mitochondrial and metabolic effects of nucleoside reverse transcriptase inhibitors (NRTIs) in mice receiving one of five single- and three dual-NRTI treatments.
- Author
-
Note R, Maisonneuve C, Lettéron P, Peytavin G, Djouadi F, Igoudjil A, Guimont MC, Biour M, Pessayre D, and Fromenty B
- Subjects
- Aminoisobutyric Acids pharmacology, Animals, Blotting, Northern, Cholesterol blood, DNA biosynthesis, DNA isolation & purification, Fatty Acids metabolism, Immunoblotting, Ketone Bodies metabolism, Lactic Acid blood, Lipid Metabolism, Liver drug effects, Liver metabolism, Male, Mice, Oxidation-Reduction, Phospholipids blood, Pyruvic Acid blood, Thymidine analogs & derivatives, Thymidine pharmacology, Triglycerides blood, Zidovudine pharmacology, Metabolism drug effects, Mitochondria drug effects, Reverse Transcriptase Inhibitors pharmacology
- Abstract
Although treatments with nucleoside reverse transcriptase inhibitors (NRTIs) can modify fat metabolism and fat distribution in humans, the mechanisms of these modifications and the roles of diverse NRTIs are unknown. We studied the mitochondrial and metabolic effects of stavudine (d4T), zidovudine (AZT), didanosine (ddI), lamivudine (3TC), zalcitabine (ddC), and three combinations (AZT-3TC, d4T-3TC, and d4T-ddI) in mice treated for 2 weeks with daily doses equivalent to the human dose per body area. Concentrations of AZT and d4T in plasma were lower when these drugs were administered with 3TC or ddI. Whatever the treatment, mitochondrial DNA was not significantly decreased in muscle, heart, brain, or white adipose tissue but was moderately decreased in liver tissue after the administration of AZT, 3TC, or d4T alone. Blood lactate was unchanged, even when NRTIs were administered at supratherapeutic doses. In contrast, the level of plasma ketone bodies increased with the administration of AZT or high doses of d4T but not with ddC, 3TC, or ddI, suggesting that the thymine moiety could be involved. Indeed, the levels of plasma ketone bodies increased in mice treated with beta-aminoisobutyric acid, a thymine catabolite. Treatment with AZT, d4T, or beta-aminoisobutyric acid increased hepatic carnitine palmitoyltransferase I (CPT-I) mRNA expression and the mitochondrial generation of ketone bodies from palmitate. In conclusion, therapeutic doses of NRTIs have no or moderate effects on mitochondrial DNA and no effects on plasma lactate in mice. However, AZT and high doses of d4T increase the levels of hepatic CPT-I, mitochondrial fatty acid beta-oxidation, and ketone bodies, and these catabolic effects are reproduced by beta-aminoisobutyric acid, a thymine metabolite.
- Published
- 2003
- Full Text
- View/download PDF
32. Interruption of nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy for 2 months has no effect on levels of human immunodeficiency virus type 1 in plasma of patients harboring viruses with mutations associated with resistance to NNRTIs.
- Author
-
Wirden M, Simon A, Schneider L, Tubiana R, Paris L, Marcelin AG, Delaugerre C, Legrand M, Herson S, Peytavin G, Katlama C, and Calvez V
- Subjects
- Alkynes, Anti-HIV Agents pharmacology, Benzoxazines, CD4 Lymphocyte Count, Cyclopropanes, Drug Administration Schedule, Drug Therapy, Combination, HIV Infections virology, HIV Reverse Transcriptase drug effects, HIV Reverse Transcriptase genetics, HIV-1 drug effects, HIV-1 enzymology, Humans, Nevirapine administration & dosage, Nevirapine pharmacology, Oxazines administration & dosage, Oxazines pharmacology, Reverse Transcriptase Inhibitors pharmacology, Viral Load, Anti-HIV Agents administration & dosage, Drug Resistance, Viral genetics, HIV Infections drug therapy, Mutation, RNA, Viral blood, Reverse Transcriptase Inhibitors administration & dosage
- Abstract
A 2-month interruption of only nonnucleoside reverse transcriptase inhibitors (NNRTIs) for patients carrying mutations associated with resistance to NNRTIs was followed by no change in either viral load or CD4 cell counts. These data suggest that these compounds have lost all of their in vivo antiviral activity in such cases.
- Published
- 2003
- Full Text
- View/download PDF
33. Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients.
- Author
-
Marcelin AG, Lamotte C, Delaugerre C, Ktorza N, Ait Mohand H, Cacace R, Bonmarchand M, Wirden M, Simon A, Bossi P, Bricaire F, Costagliola D, Katlama C, Peytavin G, and Calvez V
- Subjects
- Adult, Carbamates, Drug Administration Schedule, Drug Therapy, Combination, Female, Furans, HIV Protease Inhibitors administration & dosage, HIV-1 drug effects, Humans, Male, Middle Aged, Predictive Value of Tests, Ritonavir administration & dosage, Ritonavir blood, Sulfonamides administration & dosage, Sulfonamides blood, Viral Load, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, HIV-1 genetics, Ritonavir therapeutic use, Sulfonamides therapeutic use
- Abstract
Forty-nine protease inhibitor (PI)-experienced but amprenavir (APV)-naïve patients experiencing virological failure were treated with ritonavir (RTV) (100 mg twice a day [b.i.d.]) plus APV (600 mg b.i.d.). Patients responded to therapy with a median viral load decrease of -1.32 log(10) by week 12. The addition of low-dose RTV enhanced the minimal APV concentration in plasma (APV C(min)) up to 10-fold compared with that obtained with APV (1,200 mg b.i.d.) without RTV. Baseline PI resistance mutations (L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S, I84V) identified by univariate analysis and included in a genotypic score and APV C(min) at week 8 were predictive of the virological response at week 12. The response to APV plus RTV was significantly reduced in patients with six or more of the resistance mutations among the ones defined above. The genotypic inhibitory quotient, calculated as the ratio of the APV C(min) to the number of human immunodeficiency virus type 1 protease mutations, was a better predictor than the virological or pharmacological variables used alone. This genotypic inhibitory quotient could be used in therapeutic drug monitoring to define the concentrations in plasma needed to control replication of viruses with different levels of PI resistance, as measured by the number of PI resistance mutations.
- Published
- 2003
- Full Text
- View/download PDF
34. Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine.
- Author
-
Delaugerre C, Marcelin AG, Thibault V, Peytavin G, Bombled T, Bochet MV, Katlama C, Benhamou Y, and Calvez V
- Subjects
- Adenine administration & dosage, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Drug Therapy, Combination, HIV Infections complications, HIV Infections drug therapy, HIV Reverse Transcriptase drug effects, HIV-1 drug effects, HIV-1 enzymology, HIV-1 genetics, Hepatitis B virus drug effects, Hepatitis B, Chronic drug therapy, Humans, Lamivudine administration & dosage, Mutation, Reverse Transcriptase Inhibitors administration & dosage, Adenine analogs & derivatives, Adenine therapeutic use, Drug Resistance, Viral genetics, HIV Reverse Transcriptase genetics, Hepatitis B, Chronic complications, Lamivudine therapeutic use, Organophosphonates, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65 and 70 or any other particular HIV-1 reverse transcriptase resistance profile.
- Published
- 2002
- Full Text
- View/download PDF
35. Amprenavir inhibitory quotient and virological response in human immunodeficiency virus-infected patients on an amprenavir-containing salvage regimen without or with ritonavir.
- Author
-
Duval X, Lamotte C, Race E, Descamps D, Damond F, Clavel F, Leport C, Peytavin G, and Vilde JL
- Subjects
- Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, Carbamates, Drug Therapy, Combination, Furans, HIV Infections drug therapy, Humans, Ritonavir therapeutic use, Sulfonamides therapeutic use, Anti-HIV Agents pharmacology, HIV drug effects, HIV Infections virology, RNA, Viral drug effects, Sulfonamides pharmacology
- Abstract
The efficacy of an amprenavir (APV)-containing therapy without (group A) or with (group B) ritonavir was assessed in patients with failure of previous protease inhibitor therapy for human immunodeficiency virus (HIV) infection. The mean minimal plasma APV concentrations in groups A and B were 58 and 1,320 ng/ml, respectively, corresponding to APV inhibitory quotients of 0.2 (range, 0.03 to 0.70) and 7.0 (range, 1.4 to 145), respectively. At week 24, 2 of 8 and 13 of 14 patients in groups A and B, respectively, had <200 HIV RNA copies/ml of plasma, including 4 of 5 patients infected with APV-resistant viruses.
- Published
- 2002
- Full Text
- View/download PDF
36. Efavirenz-induced decrease in plasma amprenavir levels in human immunodeficiency virus-infected patients and correction by ritonavir.
- Author
-
Duval X, Le Moing V, Longuet C, Leport C, Vildé JL, Lamotte C, Peytavin G, and Farinotti R
- Subjects
- Alkynes, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Benzoxazines, Carbamates, Cyclopropanes, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme Inhibitors, Drug Interactions, Drug Therapy, Combination, Furans, HIV Infections drug therapy, Humans, Oxazines therapeutic use, Oxidoreductases, N-Demethylating antagonists & inhibitors, Ritonavir therapeutic use, Sulfonamides therapeutic use, Anti-HIV Agents blood, Aryl Hydrocarbon Hydroxylases, HIV Infections blood, Oxazines pharmacology, Ritonavir pharmacology, Sulfonamides blood
- Published
- 2000
- Full Text
- View/download PDF
37. Early virological failure in naive human immunodeficiency virus patients receiving saquinavir (soft gel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance.
- Author
-
Mouroux M, Yvon-Groussin A, Peytavin G, Delaugerre C, Legrand M, Bossi P, Do B, Trylesinski A, Diquet B, Dohin E, Delfraissy JF, Katlama C, and Calvez V
- Subjects
- Drug Resistance, Microbial genetics, Drug Therapy, Combination, Genotype, HIV Infections virology, HIV-1 genetics, HIV-1 isolation & purification, Humans, Phenotype, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Saquinavir pharmacokinetics, Saquinavir pharmacology, Saquinavir therapeutic use, Stavudine pharmacology, Stavudine therapeutic use, Treatment Failure, Zalcitabine pharmacology, Zalcitabine therapeutic use, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Mutation
- Abstract
The MIKADO trial was designed to evaluate the efficacy of stavudine-zalcitabine-saquinavir (soft gel capsule) [d4T-ddC-SQV(SGC)] in 36 naive patients (-3.3 log(10) units at week 24 [W24]). Among the 29 patients remaining on d4T-ddC-SQV(SGC) until W24, 10 harbored a virological failure (viral load of >200 copies/ml at W24) (group 1). To determine the reasons for therapeutic failure, genotypic and phenotypic resistance test results and SQV concentrations in plasma were analyzed and compared to those in successfully treated patients (viral load of <200 copies/ml at W24) (group 2). Reverse transcriptase and protease genotypic analyses in group 1 revealed the acquisition of only one SQV-associated mutation (L90M) in only two patients. There was no significant increase in the 50 or 90% inhibitory concentration of SQV in patients with or without the L90M mutation. However, the fact that two patients developed an L90M mutation only 4 weeks after relapse points to the need for genotypic resistance testing in the context of an initial failure of the antiretroviral regimen. At W24, the median SQV concentration in group 1 (71 ng/ml) was significantly lower than in group 2 (475 ng/ml), and the plasma SQV concentration was correlated with the viral load at W24 (r = -0.5; P<0.05) and with the drop in viral load between day 0 and W24 (r = -0.5; P<0.01). These results and the fact that the plasma SQV concentrations in the two groups prior to relapse (W12) were not significantly different strongly suggest that the early failure of this combination is not due to viral resistance but to a lack of compliance, pharmacological variability, and drug interactions or a combination of these factors.
- Published
- 2000
- Full Text
- View/download PDF
38. Kinetics of antiviral activity and intracellular pharmacokinetics of human immunodeficiency virus type 1 protease inhibitors in tissue culture.
- Author
-
Nascimbeni M, Lamotte C, Peytavin G, Farinotti R, and Clavel F
- Subjects
- HIV-1 drug effects, HIV-1 pathogenicity, HeLa Cells, Humans, Monocytes virology, Antiviral Agents pharmacokinetics, Antiviral Agents pharmacology, HIV Protease Inhibitors pharmacokinetics, HIV Protease Inhibitors pharmacology, HIV-1 enzymology
- Abstract
We have examined the kinetics of the inhibition of human immunodeficiency virus type 1 (HIV-1) particle infectivity by protease inhibitors (PIs) in cell culture, using either transfected HeLa cells or infected peripheral blood mononuclear cells (PBMCs) as producers of infectious virions. Both the kinetics of the initiation of antiviral activity after addition of the PIs to these cultures and the kinetics of restoration of virion infectivity after removal of the PIs from the treated cultures were examined. We found that the kinetics of initiation of particle infectivity inhibition produced by a high extracellular concentration (5 microM) of the inhibitors were similar for all five inhibitors tested: loss of particle infectivity was perceptible as early as 1 h after the initiation of PI treatment and increased gradually thereafter. By contrast, the durability of this antiviral effect following removal of the drug from the culture varied dramatically according to the drug studied. In transfected HeLa cells, saquinavir and nelfinavir exerted the most prolonged inhibition, with the half-lives of their antiviral activities being greater than 24 h, while ritonavir exerted an intermediate length of inhibition (18 h) and indinavir and amprenavir exerted a reproducibly shorter length of inhibition (5 h). For all five tested PIs, these kinetics were significantly faster in PBMCs than in HeLa cells. The striking differences in antiviral kinetics observed among the different PIs appear mostly due to differences in their intracellular concentrations and/or rates of cellular clearance. Our observations, although limited to tissue culture conditions, may help delineate the cellular parameters of the antiviral activities of HIV-1 PIs and further optimize the efficiencies of these antiretrovirals in vivo.
- Published
- 1999
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.