44 results on '"Peytavin, G."'
Search Results
2. Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case-series experience.
- Author
-
Delory T, Papot E, Rioux C, Charpentier C, Auge-Courtoi C, Michard F, Peytavin G, Descamps D, Matheron S, and Yazdanpanah Y
- Subjects
- Adult, Anti-HIV Agents adverse effects, CD4 Lymphocyte Count, Drug Resistance, Viral genetics, Drug Therapy, Combination, Female, Foscarnet adverse effects, HIV Infections immunology, HIV Infections virology, HIV-1 genetics, HIV-2 genetics, Heterocyclic Compounds, 3-Ring adverse effects, Heterocyclic Compounds, 3-Ring blood, Humans, Kidney drug effects, Male, Middle Aged, Oxazines, Piperazines, Pyridones, RNA, Viral blood, Viral Load, Zidovudine adverse effects, Anti-HIV Agents therapeutic use, Foscarnet therapeutic use, HIV Infections drug therapy, Heterocyclic Compounds, 3-Ring therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Salvage Therapy adverse effects, Zidovudine therapeutic use
- Abstract
Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA-ZDV-DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV-1 RNA load (pVL) >50 c/ml (>100 for HIV-2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV-1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA-ZDV-DTG containing-regimen with 48 weeks (W48) of follow-up. Out of 5 patients, 2 were infected with HIV-2. At PFA-ZDV-DTG initiation, CD4 cell count was (/mm(3) ) of 64, 40, 10, in HIV-1, and 37, 199, in HIV-2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV-1, and 3.6, 4.2, in HIV-2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1-2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV-1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV-2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV-infected patients, failing cART and without other therapeutic options, a PFA-ZDV-DTG combination therapy could be effective. Renal adverse events should be monitored., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
3. 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
4. Lack of effect of doxycycline on trough concentrations of protease inhibitors or non-nucleoside reverse transcriptase inhibitors in HIV-infected patients.
- Author
-
Abgrall S, Le Bel J, Lele N, Laouénan C, Eychenne N, Mentré F, Peytavin G, and Bouchaud O
- Subjects
- Anti-HIV Agents blood, Drug Interactions, HIV Infections drug therapy, HIV Infections metabolism, Humans, Malaria prevention & control, Protease Inhibitors blood, Reverse Transcriptase Inhibitors blood, Travel, Viral Load, Anti-HIV Agents pharmacokinetics, Antimalarials pharmacokinetics, Doxycycline pharmacokinetics, Protease Inhibitors pharmacokinetics, Reverse Transcriptase Inhibitors pharmacokinetics
- Abstract
Background: Many HIV-treated patients travel to malaria-infected zones, but very few data are available on potential interactions between antiretroviral and antimalarial drugs., Method: We performed a pharmacokinetic study on the interaction of doxycycline (100 mg/d) on 2 protease inhibitors (PIs), atazanavir and lopinavir, and 2 non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, given at usual daily doses in HIV-infected migrants native from sub-Saharan Africa included in the VIHVO ANRS-study before travelling to a sub-Saharan country. Antiretroviral trough plasma concentrations were measured at enrollment visit during the month preceding the travel before doxycycline introduction and on the week following the patients' return to France when they had been taking doxycycline for at least 15 days. Impact of doxycycline on antiretroviral concentrations was tested either with antiretroviral drugs separately or within the therapeutic classes (PI or NNRTI) in patients with an HIV RNA level <50 copies/mL at both visits and with good declared adherence. The Two One-Sided Test that was adapted to the Wilcoxon test was used to evidence the lack of interaction. Sixty-five patients receiving regimens containing atazanavir (n = 1), ritonavir-boosted atazanavir (n = 14), ritonavir-boosted lopinavir (n = 23), efavirenz (n = 17), nevirapine (n = 10) were included., Results: Lack of pharmacokinetic interaction was statistically significant when tested by therapeutic class (PI, P = .02; NNRTI, P = .005) and was not demonstrated for each antiretroviral when tested separately., Conclusion: This study is the first to assess the interaction of doxycycline on PI and NNRTI. This lack of pharmacokinetic interaction supports the choice of doxycycline as the antimalarial drug in patients treated with PI or NNRTI.
- Published
- 2013
- Full Text
- View/download PDF
5. Switch from etravirine twice daily to once daily in non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-infected patients with suppressed viremia: the Monetra study.
- Author
-
Schneider L, Ktorza N, Fourati S, Assoumou L, Courbon E, Caby F, Blanc C, Tindel M, Agher R, Marcelin AG, Calvez V, Peytavin G, and Katlama C
- Subjects
- Drug Administration Schedule, Drug Resistance, Viral genetics, Genotype, HIV Infections virology, HIV-1 genetics, Humans, Nitriles, Pilot Projects, Pyridazines administration & dosage, Pyrimidines, Reverse Transcriptase Inhibitors administration & dosage, Reverse Transcriptase Inhibitors therapeutic use, Viremia, HIV Infections drug therapy, HIV-1 drug effects, Pyridazines therapeutic use, Reverse Transcriptase Inhibitors pharmacology
- Abstract
Background: Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nucleoside reverse transcripase inhibitors (NNRTIs)., Objectives: To evaluate the capacity of once-daily ETR to maintain suppressed viremia over 48 weeks after switching from ETR twice daily in NNRTI-experienced patients., Methods: In this pilot open-label study, patients with plasma viral load (pVL) <50 copies/mL on a stable ETR 200 mg bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48 weeks. The primary endpoint was the proportion of patients with pVL <50 copies/mL at week 24. Secondary endpoints included the rate of pVL< 50 copies/mL at week 48, ETR pharmacokinetic parameters, and tolerability and resistance profile., Results: Twenty-four patients were included. They had extensive antiretroviral treatment for a median of 14 years (range, 1-19). All except for 2 had prior resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48 for virological failure (3), protocol deviation (3), and side effects (1). At week 24, 95% of patients maintained pVL< 50 copies/mL (95% CI, 78.4-99.7) and 85% at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR C(trough) level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655)., Conclusion: These results suggest that ETR is effective as a once-daily regimen in patients with prior NNRTI experience when HIV is sensitive to ETR. The stability of C(trough) concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients.
- Published
- 2012
- Full Text
- View/download PDF
6. Lopinavir/ritonavir population pharmacokinetics in neonates and infants.
- Author
-
Urien S, Firtion G, Anderson ST, Hirt D, Solas C, Peytavin G, Faye A, Thuret I, Leprevost M, Giraud C, Lyall H, Khoo S, Blanche S, and Tréluyer JM
- Subjects
- Female, Humans, Infant, Infant, Newborn, Lopinavir, Male, Models, Biological, Models, Statistical, Anti-HIV Agents pharmacokinetics, HIV Protease Inhibitors pharmacokinetics, Pyrimidinones pharmacokinetics, Reverse Transcriptase Inhibitors pharmacokinetics, Ritonavir pharmacokinetics
- Abstract
What Is Already Known About This Subject: • Lopinavir/ritonavir pharmacokinetics have been fully investigated in adults and children., What This Study Adds: • Lopinavir/ritonavir population pharmacokinetics in 96 neonates and infants from birth to less than 2 years (1.16 to 10.4 kg) showed that CL/F and V/F were dependent on body weight on an allometric basis and post-menstrual age., Aims: Because of immature hepatic metabolism, lopinavir could present specific pharmacokinetics in the first weeks of life. We aimed at determining the optimal dosing regimen in neonates and infants weighing 1 to 10.5 kg., Methods: Lopinavir/ritonavir (LPV/r) pharmacokinetics were studied in 96 infants using a population approach. RESULTS A one-compartment model described LPV/r pharmacokinetics. Normalized to a 70 kg adult using allometry, clearance (CL/F) and distribution volume (V/F) estimates were 5.87|h(-1) 70 kg(-1) and 91.7|70 kg(-1). The relative bioavailabilty, F, increased with post-menstrual age (PMA) and reached 50% of the adult value at 39.7 weeks., Conclusions: Size and PMA explained some CL/F and V/F variability in neonates/infants. Based upon trough concentration limitations, suggested LPV/r dosing regimens were 40 mg 12 h(-1), 80 mg 12 h(-1) and 120 mg 12 h(-1) in the 1-2 kg, 2-6 kg and 6-10 kg group, respectively., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)
- Published
- 2011
- Full Text
- View/download PDF
7. 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
8. Nucleoside reverse transcriptase inhibitor-sparing regimen (nonnucleoside reverse transcriptase inhibitor + protease inhibitor) was more likely associated with resistance comparing to nonnucleoside reverse transcriptase inhibitor or protease inhibitor + nucleoside reverse transcriptase inhibitor in the randomized ANRS 121 trial.
- Author
-
Soulié C, Assoumou L, Ghosn J, Duvivier C, Peytavin G, Ait-Arkoub Z, Molina JM, Costagliola D, Katlama C, Calvez V, and Marcelin AG
- Subjects
- Antiretroviral Therapy, Highly Active methods, Drug Resistance, Viral, HIV Infections virology, HIV Protease Inhibitors therapeutic use, HIV Reverse Transcriptase antagonists & inhibitors, HIV-1 genetics, HIV-1 isolation & purification, Humans, Mutation, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
The use of nonnucleoside reverse transcriptase inhibitor (NNRTI) + protease inhibitor regimen for the treatment of antiretroviral-naive patients was less successful than classical nucleoside reverse transcriptase inhibitor (NRTI) based regimen and associated with more resistance for protease inhibitors and NNRTIs. The selection for NNRTI resistance was particularly observed in patients with high viral load (>100 000 copies/ml) and low efavirenz trough levels (<1100 ng/ml). Contrary to the results observed in trials evaluating mono or dual protease inhibitors strategies, gag gene mutations were not involved in the low efficacy of this strategy. The NNRTI + protease inhibitor strategy should not be recommended as an antiretroviral first-line regimen, particularly in patients with high viral load at baseline.
- Published
- 2009
- Full Text
- View/download PDF
9. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial.
- Author
-
Duvivier C, Ghosn J, Assoumou L, Soulié C, Peytavin G, Calvez V, Génin MA, Molina JM, Bouchaud O, Katlama C, and Costagliola D
- Subjects
- Absorptiometry, Photon, Adipose Tissue diagnostic imaging, Adult, Africa South of the Sahara, Anti-Retroviral Agents therapeutic use, CD4 Lymphocyte Count, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Treatment Outcome, Viral Load, Anti-Retroviral Agents adverse effects, HIV Infections drug therapy, HIV-Associated Lipodystrophy Syndrome chemically induced, Reverse Transcriptase Inhibitors adverse effects
- Abstract
Objectives: The aim of this study was to evaluate the impact on body fat of nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens compared with NRTI-containing therapy in HIV-1-infected antiretroviral (ARV)-naive patients., Methods: A randomized, multicentre, open-label trial in ARV-naive patients. Subjects were randomized (2:1:1) to receive: (i) an NRTI-sparing regimen consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a boosted protease inhibitor (PI/r); or (ii) an NRTI-containing regimen of (a) a PI/r plus two NRTIs or (b) an NNRTI plus two NRTIs. The primary endpoint was the change in subcutaneous limb fat measured by dual-energy X-ray absorptiometry at week (W) 96. Secondary endpoints included the proportion of patients with treatment failure, plasma HIV-RNA (pVL) <50 copies/mL and safety., Results: One hundred and seventeen patients were enrolled between November 2003 and May 2004: 26% female; 42% from sub-Saharan Africa; median plasma HIV-RNA (pVL) 5.1 log(10) copies/mL; median CD4 count 207 cells/mm(3). A planned interim analysis demonstrated significantly lower treatment and virological responses with the NRTI-sparing strategy, resulting in premature study termination on 19 July 2005. The proportion of patients who remained on their assigned treatment strategy and had pVL <50 copies/mL on the NRTI-sparing regimen was 60.0%, compared with 82.5% on the NRTI-containing regimen at W24 (P = 0.009) and 66.7% and 82.5%, respectively, at W48 (P = 0.059). Treatment failure was associated with the NRTI-sparing strategy in patients with suboptimal adherence and with being from sub-Saharan Africa. No differences in fat distribution were noted., Conclusions: An initial NRTI-sparing regimen is less successful and virologically less potent than standard NRTI-containing regimen and should not therefore be used as the first line of treatment.
- Published
- 2008
- Full Text
- View/download PDF
10. Viral efficacy maintained and safety parameters improved with a reduced dose of stavudine: a pilot study.
- Author
-
Ait-Mohand H, Bonmarchand M, Guiguet M, Slama L, Marguet F, Behin A, Amellal B, Bennai Y, Peytavin G, Calvez V, Pialoux G, Murphy R, and Katlama C
- Subjects
- Adult, Aged, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Drug Administration Schedule, Female, HIV Infections virology, Humans, Male, Middle Aged, Pilot Projects, RNA, Viral drug effects, Reverse Transcriptase Inhibitors pharmacokinetics, Stavudine pharmacokinetics, Treatment Outcome, Viral Load, HIV Infections drug therapy, HIV-1, Reverse Transcriptase Inhibitors administration & dosage, Stavudine administration & dosage
- Abstract
Objectives: Stavudine (d4T) is a potent but potentially toxic nucleoside reverse transcriptase inhibitor that is still widely used in developing countries. This study's aim was to determine the efficacy and safety profile of lower-dose d4T., Methods: Multi-centre, open-label, single-arm, pilot, 48-week study in French patients weighing >60 kg with viral load <400 HIV-1 RNA copies/mL who were receiving d4T 40 mg twice daily and then switched to 30 mg twice daily. The primary endpoint was the proportion with plasma viral load <400 copies/mL at week 24. Secondary endpoints included the proportion with <50 copies/mL at weeks 24 and 48, changes in mitochondrial DNA, CD4 cell count and pharmacokinetics, and clinical and laboratory safety., Results: Fifty-seven patients enrolled. Baseline CD4 count was 584 cells/microL; viral loads were <400 copies/mL and <50 copies/mL in 100% and 89%, respectively. Prior antiretroviral drug exposure was 6.9 years, d4T exposure was 6.3 years. Fifty-six out of 57 (98%) patients had viral load <400 copies/mL and 51 (89%) had viral load <50 copies/mL at week 24. Median CD4 count increased by 63 cells/microL at week 48 (P=0.006). At 48 weeks, total cholesterol decreased by 0.24 mmol (P=0.02), high-density lipoprotein cholesterol by 0.15 mmol (P=0.0001) and alanine aminotransferase by 5.74 mg/dL (P=0.01). Paired baseline DNA and week 24 RNA mutations were unchanged. Mitochondrial DNA (copies/cell) content increased from 672+/-254 to 682+/-269. d4T area under the plasma concentration time curve (AUC) decreased by 31% (P=0.003) and C(max) by 44% (P=0.004). Clinical and laboratory parameters improved or were unchanged., Conclusions: Reduced-dose d4T is effective with improved safety parameters.
- Published
- 2008
- Full Text
- View/download PDF
11. 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
12. HIV drug resistance after the use of generic fixed-dose combination stavudine/lamivudine/nevirapine as standard first-line regimen.
- Author
-
Marcelin AG, Jarrousse B, Derache A, Ba M, Dakouo ML, Doumbia A, Haidara I, Maïga A, Carcelain G, Peytavin G, Katlama C, and Calvez V
- Subjects
- Adult, Drug Combinations, Drugs, Generic, Female, Genes, MDR, HIV Infections blood, HIV Infections immunology, HIV-1 genetics, Humans, Lamivudine blood, Lamivudine therapeutic use, Male, Mali, Mutation, Nevirapine blood, Nevirapine therapeutic use, RNA, Viral blood, Stavudine blood, Stavudine therapeutic use, Treatment Failure, Viral Load, Developing Countries, Drug Resistance, Multiple, Viral, HIV Infections drug therapy, HIV-1 physiology, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Early failures to stavudine/lamivudine/nevirapine used as a generic fixed-dose combination in Mali showed resistance mutations in 50% of cases (mostly M184V and Y181C). No thymidine analogue mutations were seen, suggesting that most nucleoside reverse transcriptase inhibitors could be used in a second-line regimen. This highlights the importance of the accessibility of HIV-RNA assays for monitoring treated patients in resource-poor countries to detect early virological failure in order to preserve future therapeutic options.
- Published
- 2007
- Full Text
- View/download PDF
13. Efficacy and safety of tenofovir double-dose in treatment-experienced HIV-infected patients: the TENOPLUS study.
- Author
-
Dominguez S, Ghosn J, Peytavin G, Izzedine H, Wirden M, Ktorza N, Miller M, Aubron-Olivier C, Trylesinski A, Calvez V, Deray G, and Katlama C
- Subjects
- Adenine administration & dosage, Adenine pharmacokinetics, Adenine therapeutic use, Adult, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections virology, HIV-1 genetics, HIV-1 physiology, Humans, Male, Middle Aged, Mutation, Pilot Projects, RNA, Viral blood, Tenofovir, Viral Load, Adenine analogs & derivatives, Anti-HIV Agents administration & dosage, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Organophosphonates administration & dosage, Organophosphonates pharmacokinetics, Organophosphonates therapeutic use, Reverse Transcriptase Inhibitors administration & dosage, Reverse Transcriptase Inhibitors pharmacokinetics, Reverse Transcriptase Inhibitors pharmacology, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Drug resistance is an increasing problem in the treatment of HIV infection. Tenofovir has been shown to inhibit HIV replication even with thymidine-associated resistance mutations (TAMs) if they are limited to two or less. Double-dose of tenofovir disoproxil fumarate (TDF) (600 mg QD) was used to determine weather the drug could be virologically effective in patients harbouring HIV-strains resistant to nucleoside analogues (NRTI). A pilot, open, non-comparative add-on study, where patients failing a current antiretroviral regimen, with at least two TAMs, and naive for tenofovir, were given tenofovir 600 mg once-daily for 4 weeks, in addition to their current failing antiretroviral regimen. The primary end-point was the percentage of patients with plasma viral load (VL) reduction of at least 0.8 log(10) between baseline and week 4 (W4). Ten patients were enrolled. At baseline, the median viral load was 3.66 log(10) copies/ml (range 3.13-4.03) and the median CD4 cell count was 407/mm(3) (range 136-1102). The percentage of patients with reduction the viral load > or =0.8 log(10) was 40% at W4. After 4 weeks of treatment with tenofovir 600 mg, the median decrease in the viral load was -0.61 log(10) (range -0.05; -0.88) and the median gain of CD4 was +109/mm(3). Despite a twofold increase tenofovir plasma concentrations, no serious drug-related adverse event were recorded except for one patient experiencing an de Fanconi syndrome at week 2. This add-on pilot study supports the concept of double dose tenofovir to virologically overcome the decreased sensitivity of NRTI-resistant viruses. However, the safety of this regimen needs to be considered carefully.
- Published
- 2007
- Full Text
- View/download PDF
14. High doses of stavudine induce fat wasting and mild liver damage without impairing mitochondrial respiration in mice.
- Author
-
Igoudjil A, Abbey-Toby A, Begriche K, Grodet A, Chataigner K, Peytavin G, Maachi M, Colin M, Robin MA, Lettéron P, Feldmann G, Pessayre D, and Fromenty B
- Subjects
- Adipose Tissue, White metabolism, Adipose Tissue, White pathology, Administration, Oral, Aminoisobutyric Acids metabolism, Animals, Carnitine administration & dosage, Fatty Acids metabolism, Hepatocytes metabolism, Hepatocytes ultrastructure, Ketone Bodies blood, Ketone Bodies metabolism, Leptin analysis, Leptin metabolism, Lipodystrophy blood, Lipodystrophy metabolism, Liver metabolism, Liver physiopathology, Liver Diseases blood, Liver Diseases metabolism, Male, Mice, Reverse Transcriptase Inhibitors adverse effects, Stavudine adverse effects, Stearoyl-CoA Desaturase metabolism, Transaminases blood, Transaminases metabolism, Vitamin B Complex administration & dosage, Wasting Syndrome metabolism, Chemical and Drug Induced Liver Injury, Lipodystrophy chemically induced, Mitochondria, Liver metabolism, Reverse Transcriptase Inhibitors administration & dosage, Stavudine administration & dosage, Wasting Syndrome chemically induced
- Abstract
Objective: Stavudine (d4T), a nucleoside reverse-transcriptase inhibitor (NRTI), can induce lipoatrophy, fatty liver, hyperlactataemia and abnormal liver tests. NRTI toxicity is usually ascribed to mitochondrial DNA (mtDNA) depletion and impaired mitochondrial respiration. However, NRTIs could have effects unrelated to mtDNA. Recently, we reported that 100 mg/kg/day of d4T stimulated fatty acid oxidation (FAO) in mouse liver, and reduced body fatness without depleting white adipose tissue (WAT) mtDNA. We hypothesized that higher d4T doses could further reduce adiposity, while inhibiting hepatic FAO., Methods: Mice were treated for 2 weeks with d4T (500 mg/kg/day), L-carnitine (200 mg/kg/day) or both drugs concomitantly. Body fatness was assessed by dual energy X-ray absorptiometry, and investigations were performed in plasma, liver, muscle and WAT., Results: D4T reduced the gain of body adiposity, WAT leptin, whole body FAO and plasma ketone bodies, and increased liver triglycerides and plasma aminotransferases with mild ultrastructural abnormalities in hepatocytes. Plasma lactate and respiratory chain activities in tissues were unchanged. Stearoyl-CoA desaturase (SCD-1), an enzyme negatively regulated by leptin, was overexpressed in liver. High doses of beta-aminoisobutyric acid (BAIBA), a d4T catabolite, increased plasma ketone bodies. Although L-carnitine did not correct body adiposity, it prevented d4T-induced impairment of FAO and liver abnormalities., Conclusions: D4T overdosage triggers fat wasting, leptin insufficiency and mild liver damage, without causing respiratory chain dysfunction. Overexpression of SCD-1 reduces fatty acid oxidation and overcomes the stimulating effect of BAIBA on hepatic FAO. L-carnitine does not correct leptin insufficiency but prevents d4T-induced impairment of FAO and liver damage.
- Published
- 2007
15. Presence of numerous stop codons in HIV-1 reverse transcriptase proviral DNA sequences from patients with virological response to HAART.
- Author
-
Makinson A, Masquelier B, Taieb A, Peytavin G, Waldner-Combernoux A, Collin G, Chêne G, Brun-Vézinet F, Raffi F, Le Moing V, Leport C, and Descamps D
- Subjects
- Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, DNA, Viral blood, HIV Infections drug therapy, HIV Infections immunology, Humans, Mutation, Treatment Outcome, Codon, Terminator, HIV Infections virology, HIV Reverse Transcriptase genetics, HIV-1 genetics, Proviruses genetics, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
The impact of proviral DNA reverse transcriptase mutations on virological failure was evaluated in 50 HIV-1 HAART-treated patients switching from a protease inhibitor to a non-nucleoside reverse transcriptase inhibitor. Neither the M184I/V mutation detected in 12 patients nor stop codons at tryptophane positions detected in 13 patients were associated with virological failure. Stop codons appeared under successful therapy in 12 patients. Their presence should be assessed in studies with higher statistical power.
- Published
- 2006
- Full Text
- View/download PDF
16. Low risk of nevirapine resistance mutations in the prevention of mother-to-child transmission of HIV-1: Agence Nationale de Recherches sur le SIDA Ditrame Plus, Abidjan, Cote d'Ivoire.
- Author
-
Chaix ML, Ekouevi DK, Rouet F, Tonwe-Gold B, Viho I, Bequet L, Peytavin G, Toure H, Menan H, Leroy V, Dabis F, and Rouzioux C
- Subjects
- Cote d'Ivoire, Drug Therapy, Combination, Female, HIV Infections transmission, HIV Infections virology, Humans, Infant, Newborn, Lamivudine therapeutic use, Mothers, Mutation, Nevirapine therapeutic use, Perinatal Care methods, Pregnancy, Pregnancy Complications, Infectious, Viral Load, Zidovudine therapeutic use, Drug Resistance, Viral genetics, HIV Infections prevention & control, HIV-1, Infectious Disease Transmission, Vertical prevention & control, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
The frequency of resistance mutations was estimated in the cohort of Agence Nationale de Recherches sur le SIDA Ditrame Plus, a study that evaluated the combination of short-course zidovudine (ZDV) plus lamivudine (3TC) and single-dose nevirapine (SD-NVP) followed by 3 days of postpartum ZDV plus 3TC for the prevention of mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1). The frequency with which resistance mutations were detected in mothers at week 4 postpartum was 1.14% (95% confidence interval [CI], 0.03%-6.17%) for NVP and 8.33% (95% CI, 3.66%-15.76%) for 3TC. In multivariate analysis, 3TC resistance was associated with a longer duration of ZDV plus 3TC prepartum prophylaxis (P=.009). This regimen, which is feasible in resource-limited settings, prevents most peripartum HIV-1 transmission and minimizes the development of NVP resistance.
- Published
- 2006
- Full Text
- View/download PDF
17. Virological and pharmacological factors associated with virological response to salvage therapy after an 8-week of treatment interruption in a context of very advanced HIV disease (GigHAART ANRS 097).
- Author
-
Delaugerre C, Peytavin G, Dominguez S, Marcelin AG, Duvivier C, Gourlain K, Amellal B, Legrand M, Raffi F, Costagliola D, Katlama C, and Calvez V
- Subjects
- Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Drug Administration Schedule, Drug Resistance, Viral genetics, Drug Therapy, Combination, HIV Protease genetics, HIV-1 classification, HIV-1 genetics, Humans, Mutation, RNA, Viral blood, Reverse Transcriptase Inhibitors pharmacology, Reverse Transcriptase Inhibitors therapeutic use, Treatment Outcome, Viral Load, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Reverse Transcriptase Inhibitors administration & dosage, Salvage Therapy
- Abstract
Both highly potent antiretroviral drug rescue multi therapy and treatment interruption (TI) have been suggested to be effective in HIV-1 infected-patients with multiple treatment failure. GigHAART-ANRS 097 was the only randomized trial during which an 8-week TI was beneficial in heavily pre-treated patients with multi-drug resistant virus on resuming a multiple-drug salvage regimen. The aim of this study was to analyze virological and pharmacological factors associated with a virological response. Clonal resistance analysis showed that although the viral population was highly mutated and nearly monoclonal at baseline, the 8-week interruption therapy allowed the re-emergence of more susceptible quasispecies to the subsequent salvage therapy, which were not detected by classical genotypic resistance testing. The fact that not every viral clone harbored all resistance viral mutations could explain a part of the virological response to a six to eight drug regimen for patients enrolled in the TI group. This phenomenon was associated with a transient virological response after the use of a GigHAART therapy, but was followed by the re-emergence of baseline resistance pattern and acquisition of additional mutations in patients failing this strategy. A combined factor of protease inhibitor (PI) concentration and genotypic score, expressed as a genotypic inhibitory quotient (GIQ), was used to assess the importance of genotypic resistance and plasma drug levels in the rate of response to multiple PI combination. The GIQ of each PI used in the regimen was not associated with virological success. However, the sum of PI GIQs was predictive of a virological response. These results suggest that pharmacological enhancement might overcome viral resistance and that there is some benefit in adding the activity of several boosted-PIs to improve the response to a salvage regimen., ((c) 2005 Wiley-Liss, inc.)
- Published
- 2005
- Full Text
- View/download PDF
18. Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study.
- Author
-
Landman R, Descamps D, Peytavin G, Trylesinski A, Katlama C, Girard PM, Bonnet B, Yeni P, Bentata M, Michelet C, Benalycherif A, Brun Vezinet F, Miller MD, and Flandre P
- Subjects
- Adult, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Dideoxynucleosides blood, Female, Genotype, HIV Infections blood, HIV Infections virology, Humans, Lamivudine blood, Male, Middle Aged, Patient Compliance, Pilot Projects, Prospective Studies, RNA, Viral blood, Reverse Transcriptase Inhibitors blood, Dideoxynucleosides administration & dosage, HIV Infections drug therapy, HIV-1 genetics, Lamivudine administration & dosage, Reverse Transcriptase Inhibitors administration & dosage
- Abstract
Background: To assess the efficacy and safety of the triple NRTI combination of abacavir (ABC), lamivudine (3TC), and tenofovir (TDF) in a once-daily regimen., Method: 38 HIV-naive patients (pts) were treated in a prospective open-arm study over 48 weeks (W48). Virological failure was defined as never achieving plasma HIV-1 RNA < 400 copies/mL or rebound of > or = 0.7 log10., Results: 12/36 (33%) pts had virologic failure at W24 and 10 additional pts had HIV RNA > 50 copies/mL at W12 or W24. There was a significant association between baseline viral load (VL) and virologic failure in 0%, 29%, and 64% pts with baseline VL levels < 4, 4-5, and > 5 log10 copies/mL, respectively (p = .014). 76% of pts developed K65R and M184V/I mutations by W24, and 19% developed M184V/I alone. At W4, 86% of pts had adequate plasma Cmin for the 3 drugs. 14 pts with K65R and M184V/I were given a rescue therapy with a successful outcome (< 50 copies/mL; median follow-up 48 weeks)., Conclusion: Convergent genetic pathway to resistance, in conjunction with lower antiretroviral potency, may explain the high rate of selection K65R and M184V mutations. These mutations did not appear to have a negative effect on rescue therapy with a variety of regimens.
- Published
- 2005
- Full Text
- View/download PDF
19. 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
20. HIV-1 intermittent viraemia in patients treated by non-nucleoside reverse transcriptase inhibitor-based regimen.
- Author
-
Martinez V, Marcelin AG, Morini JP, Deleuze J, Krivine A, Gorin I, Yerly S, Perrin L, Peytavin G, Calvez V, and Dupin N
- Subjects
- Adult, Aged, Alkynes, Benzoxazines, CD4 Lymphocyte Count, Cyclopropanes, Female, Humans, Male, Middle Aged, Nevirapine therapeutic use, Oxazines therapeutic use, Retrospective Studies, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Reverse Transcriptase antagonists & inhibitors, Reverse Transcriptase Inhibitors therapeutic use, Viremia etiology
- Abstract
Background: It has been demonstrated that, in patients treated by protease-inhibitor-based regimen, intermittent viraemia occurred frequently and was associated with higher concentrations of residual replication but not with virological failure. Risk factors associated with intermittent viraemia and its impact in patients treated by non-nucleoside-reverse-transcriptase-inhibitor-based (NNRTI) regimen need to be evaluated., Methods: We analyzed the occurrence of blips (one HIV-1 RNA > 50 copies/ml with a subsequent value < 50 copies/ml), the level of these blips (between 3 and 50 copies/ml) and their effect on CD4 cell count and the occurrence of virological failure in 43 patients with stable suppression of HIV-1 plasma viraemia (< 50 copies/ml) under NNRTI-based therapy., Results: Eight out of 43 patients had one episode of blips during the follow-up (median = 350 copies/ml). Comparing patients with and without blips, the median level of HIV-1 RNA at baseline was 7.5 versus 3 copies/ml (P = 0.008), respectively. Patients with blips had a significantly lower CD4 cell count after 12 and 18 months than the others. Plasma concentrations of NNRTI before, during, and after the blips were adequate. In addition, the occurrence of blips was not associated with virological failure., Conclusion: These results suggest that blips may reflect ongoing viraemia of below 50 copies/ml and can impair the CD4 cell count recovery under an NNRTI regimen. The impairment of CD4 cell count recovery seems to be affected more by the occurrence of blips than by the level of viraemia (< 50 copies/ml) itself. Nevertheless, despite a tight genetic barrier for resistance with NNRTI drugs, no virologic failure occurred during the follow-up.
- Published
- 2005
- Full Text
- View/download PDF
21. Intermittent viremia during first-line, protease inhibitors-containing therapy: significance and relationship with drug resistance.
- Author
-
Masquelier B, Pereira E, Peytavin G, Descamps D, Reynes J, Verdon R, Fleury H, Garraffo R, Chêne G, Raffi F, and Brun-Vézinet F
- Subjects
- Drug Therapy, Combination, HIV Infections virology, HIV-1 drug effects, HIV-1 enzymology, HIV-1 genetics, HIV-1 physiology, Humans, Patient Compliance, RNA, Viral blood, Viral Load, Viremia drug therapy, Anti-HIV Agents therapeutic use, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Viremia virology
- Abstract
Background: In HIV-infected patients on first-line antiretroviral therapy, the significance of intermittent viremia and their relationship with drug resistance remain unclear., Objective: To study the virological characteristics of intermittent viremia (IV) and the association between IV and later virological failure (VF) in patients on a first-line, PI-containing therapy., Study Design: Antiretroviral-naive patients were enrolled in the APROVIR substudy of the prospective, multicenter APROCO cohort at the time they initiated a PI-containing therapy and were followed-up at month 1 and every 2 months. IV was defined as plasma HIV-1 RNA > 500 copies/ml on a single specimen. VF were defined as: (1) viral rebound on two consecutive plasma specimens with HIV-1 RNA > 500 copies/ml after an initial response below 500 copies/ml, or (2) persistence of plasma HIV-1 RNA> or =500 copies/ml during the first year of follow-up. Genotypic resistance analysis was performed at baseline and at the time of IV. PI plasma concentrations were determined at the time of IV., Results: IV was found in 20/219 patients in a 2 years follow-up. The occurrence of IV in the first year of therapy was associated with a higher risk of virological failure during the second year (p = 0.03). Genotypic resistance at the time of IV was found in only 4/16 patients and was not predictive of a subsequent virological failure. PI plasma levels suggested lack of adherence in 50% of patients with IV., Conclusion: The occurrence of IV > 500 copies/ml among patients on first-line, PI-containing ART is suggestive of a lack of adherence rather than the selection of resistant variants and should lead to an intensification of adherence monitoring in order to reduce the risk of subsequent VF.
- Published
- 2005
- Full Text
- View/download PDF
22. Letter. In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene.
- Author
-
Damond F, Collin G, Matheron S, Peytavin G, Campa P, Delarue S, Taieb A, Bénard A, Chêne G, Brun-Vézinet F, and Descamps D
- Subjects
- HIV Infections virology, HIV-2 enzymology, Humans, Phenotype, Drug Resistance, Multiple, Viral genetics, HIV-2 drug effects, HIV-2 genetics, Mutation genetics, RNA-Directed DNA Polymerase genetics, Reverse Transcriptase Inhibitors pharmacology
- Abstract
In HIV-2 infection, many studies have reported a high frequency of selection of the Q151M mutation, but its impact on phenotypic susceptibility of HIV-2 isolates remains unclear. Four HIV-2 infected patients from the French ANRS HIV-2 cohort, with evidence of Q151M mutation in both plasma and available peripheral blood mononuclear cells (PBMCs) co-cultivated supernatants, were selected. In vitro phenotypic susceptibilities to different nucleoside reverse transcriptase inhibitors (NRTIs) were determined using a PBMC assay. In HIV-2 isolates, the Q151M mutation alone impacts only the phenotypic susceptibility to stavudine and abacavir. A decrease in susceptibility to all NRTIs was observed when Q151M was selected with V111I, a mutation of unknown impact on HIV-1 resistance. Clinical relevance of these phenotypic susceptibility results needs to be evaluated in HIV-2 treated patients.
- Published
- 2005
23. Evolution of protease and reverse transcriptase inhibitor resistance-associated mutations in HIV-1-infected protease inhibitor-treated patients with persistent low viraemia.
- Author
-
Duval X, Descamps D, Breton G, Darmon S, Ecobichon JL, Delarue S, Peytavin G, Leport C, Vildé JL, and Brun-Vézinet F
- Subjects
- Antiretroviral Therapy, Highly Active, Drug Resistance, Viral genetics, Humans, Mutation, Retrospective Studies, Viremia drug therapy, Viremia virology, HIV Infections drug therapy, HIV Infections virology, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, HIV-1 genetics, Reverse Transcriptase Inhibitors pharmacology
- Published
- 2005
24. Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs.
- Author
-
Boffito M, Acosta E, Burger D, Fletcher CV, Flexner C, Garaffo R, Gatti G, Kurowski M, Perno CF, Peytavin G, Regazzi M, and Back D
- Subjects
- Drug Interactions, HIV Infections drug therapy, Humans, Practice Guidelines as Topic, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents pharmacology, Drug Monitoring trends, Reverse Transcriptase Inhibitors pharmacokinetics, Reverse Transcriptase Inhibitors pharmacology
- Abstract
The consensus of current international guidelines for the treatment of HIV infection is that data on therapeutic drug monitoring (TDM) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (Pls) provide a framework for the implementation of TDM in certain defined scenarios in clinical practice. However, the utility of TDM is considered to be on an individual basis until more data are obtained from large clinical trials showing the benefit of TDM. In April 2004, a panel of experts met for the second time in Rome, Italy. This was following the inaugural meeting in Perugia, Italy, in October 2000, which resulted in the manuscript published in AIDS 2002, 16(Suppl 1):S5-S37. The objectives of this second meeting were to review and update the numerous questions surrounding TDM of antiretroviral drugs and discuss the clinical utility, current concerns and future prospects of drug concentration monitoring in the care of HIV-1-infected individuals. A major focus of the meeting was to discuss and critically analyse recent and precedent clinical drug-drug interaction data to provide a clear framework of the pharmacological basis of how one drug may impact the disposition of another. This report, which has been updated to include material published or presented at international conferences up to the end of December 2004, reviews recent pivotal pharmacokinetic interaction data and provides advice to clinical care providers on how some drug-drug interactions may be prevented, avoided or managed, and, when data are available, on what dose adjustments and interventions should be performed.
- Published
- 2005
25. Selection of K65R mutation in HIV-2-infected patients receiving tenofovir-containing regimen.
- Author
-
Damond F, Matheron S, Peytavin G, Campa P, Taieb A, Collin G, Delaunay C, Chêne G, Brun-Vézinet F, and Descamps D
- Subjects
- Adenine administration & dosage, Adenine blood, Cohort Studies, Drug Therapy, Combination, France, Genotype, HIV Infections blood, HIV Infections virology, HIV Reverse Transcriptase, HIV-2 isolation & purification, Humans, Organophosphonates administration & dosage, Organophosphonates blood, Reverse Transcriptase Inhibitors administration & dosage, Tenofovir, Time Factors, Adenine analogs & derivatives, Adenine therapeutic use, HIV Infections drug therapy, HIV-2 genetics, Mutation, Organophosphonates therapeutic use, RNA-Directed DNA Polymerase genetics, Reverse Transcriptase Inhibitors therapeutic use
- Published
- 2004
26. Virologic outcome after switching from a nucleoside reverse transcriptase inhibitor to tenofovir in patients with undetectable HIV-1 RNA plasma level.
- Author
-
Wirden M, Marcelin AG, Tubiana R, Valantin MA, Ghosn J, Duvivier C, Dominguez S, Paris L, Agher R, Peytavin G, Katlama C, and Calvez V
- Subjects
- Adenine therapeutic use, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, Drug Resistance, Viral, Humans, Retrospective Studies, Tenofovir, Treatment Outcome, Viremia drug therapy, Viremia virology, Adenine analogs & derivatives, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, HIV-1 isolation & purification, Organophosphonates therapeutic use, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use
- Published
- 2004
- Full Text
- View/download PDF
27. Usefulness of therapeutic drug monitoring of antiretrovirals in routine clinical practice.
- Author
-
Duong M, Golzi A, Peytavin G, Piroth L, Froidure M, Grappin M, Buisson M, Kohli E, Chavanet P, and Portier H
- Subjects
- Diagnostic Tests, Routine statistics & numerical data, France epidemiology, HIV Infections blood, HIV Protease Inhibitors therapeutic use, Humans, Pharmacy Service, Hospital standards, Reverse Transcriptase Inhibitors therapeutic use, Drug Monitoring statistics & numerical data, HIV Infections drug therapy, HIV Protease Inhibitors pharmacokinetics, Pharmacy Service, Hospital statistics & numerical data, Reverse Transcriptase Inhibitors pharmacokinetics
- Abstract
Background: Clinical trials have shown that therapeutic drug monitoring (TDM) of antiretrovirals (ARV) improves patient care. However, little is known about the usefulness of TDM in routine practice., Method: We reviewed all the trough concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors that were performed for therapeutic failure, suspected drug toxicity, or routine purposes., Results: Between 1998 and 2001, 146 TDMs were done in 109 HIV patients. Of the 48 patients with therapeutic failure, 62% had resistance to ARV with adequate ARV concentrations, 16% had insufficient drug exposure without any ARV resistance mutations, and 16% combined both resistance and suboptimal drug concentrations. Subsequent therapeutic interventions (increasing adherence and/or changing HAART) resulted in an undetectable viral load in 37.5% of the patients (14/48). Five (24%) of 21 patients with suspected drug toxicity had high drug concentrations associated with side effects. In all the cases, adverse events regressed after reduction of drug dosage. Of the 77 TDMs done for routine purposes, 26% were outside the therapeutic range., Conclusion: The data show that TDM of ARVs in the clinical setting provides important information that can be used to improve the management of HIV patients receiving antiretroviral therapy.
- Published
- 2004
- Full Text
- View/download PDF
28. Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients.
- Author
-
Masquelier B, Tamalet C, Montès B, Descamps D, Peytavin G, Bocket L, Wirden M, Izopet J, Schneider V, Ferré V, Ruffault A, Palmer P, Trylesinski A, Miller M, Brun-Vézinet F, and Costagliola D
- Subjects
- Adenine blood, Codon, Cohort Studies, France, Genotype, HIV Infections blood, HIV Infections virology, HIV Reverse Transcriptase antagonists & inhibitors, HIV Reverse Transcriptase genetics, HIV-1 genetics, HIV-1 isolation & purification, Humans, Multivariate Analysis, Organophosphonates blood, Point Mutation drug effects, RNA, Viral blood, Tenofovir, Adenine analogs & derivatives, Adenine therapeutic use, HIV Infections drug therapy, HIV-1 drug effects, Organophosphonates therapeutic use, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objective: To assess the genotypic determinants of the virological response to tenofovir disoproxil fumarate (TDF) in a multicentre cohort of antiretroviral (ARV)-experienced patients receiving TDF as a part of a salvage therapy., Methods: HIV-1 genotype was assessed at baseline in a subgroup of 161 patients of the French expanded access program receiving a stable TDF-including regimen for 3 months or more. Reverse transcriptase mutations associated with the viral load decrease at month 3 with a P-value <0.15 were retained for the construction of a mutation score. The score was then validated using a multivariate analysis and bootstrap resampling method., Results: The strongest association with decrease in viral load was observed with a set of seven mutations (TDF mutation score) that consisted of M41L, E44D, D67N, T69D/N/S, L74V, L210W and T215Y/F RT mutations. The RT K65R mutation and the insertions at codon 69 were not included in the analysis due to low prevalences. A TDF mutation score of < or = 2 predicted the absence of resistance to TDF and > or = 6 mutations predicted resistance to TDF with corresponding reductions in viral load of -1.3 +/- 1.1, and +0.1 +/- 0.7 log10 copies/ml, respectively. In patients with a TDF mutation score of 3-5, the decrease in viral load was -0.8 +/- 1.0 log10 copies/ml and was considered possibly resistant. In the multivariate analysis, a TDF mutation score > or = 6, previous use of amprenavir, indinavir and lopinavir, and co-prescription of didanosine were associated with a worse virological response. The bootstrap analysis showed the robustness of the TDF mutation score., Conclusion: In ARV-experienced patients receiving TDF-containing regimens, a score derived from seven reverse transcriptase mutations was shown to be independently predictive of the virological response.
- Published
- 2004
29. 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
30. Tubulopathy consecutive to tenofovir-containing antiretroviral therapy in two patients infected with human immunodeficiency virus-1.
- Author
-
Breton G, Alexandre M, Duval X, Prie D, Peytavin G, Leport C, and Vildei JL
- Subjects
- Adenine administration & dosage, Anti-HIV Agents administration & dosage, Drug Therapy, Combination, Fanconi Syndrome etiology, HIV-1 drug effects, Humans, Organophosphorus Compounds administration & dosage, Polyuria etiology, Reverse Transcriptase Inhibitors administration & dosage, Tenofovir, Adenine adverse effects, Adenine analogs & derivatives, Anti-HIV Agents adverse effects, HIV Infections drug therapy, Hypophosphatemia etiology, Kidney Tubules pathology, Organophosphonates, Organophosphorus Compounds adverse effects, Reverse Transcriptase Inhibitors adverse effects
- Abstract
Tenofovir disopril fumarate, a new nucleotide analogue against human immunodeficiency virus-1 (HIV-1), can induce hypophosphataemia, the mechanism of which is unclear. Moreover, a renal tubulopathy can occur in long-term treated patients, as observed in 2 HIV-1-infected patients after 12 months of tenofovir therapy, with polyuria-polydipsia, proteinuria, glycosuria and amino-aciduria, which resolved after discontinuation of tenofovir. The risk of renal tubulopathy symptoms in patients on long-term tenofovir therapy should be noted.
- 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. Predictors of the virological response to a change in the antiretroviral treatment regimen in HIV-1-infected patients enrolled in a randomized trial comparing genotyping, phenotyping and standard of care (Narval trial, ANRS 088).
- Author
-
Vray M, Meynard JL, Dalban C, Morand-Joubert L, Clavel F, Brun-Vézinet F, Peytavin G, Costagliola D, and Girard PM
- Subjects
- Adult, Anti-HIV Agents pharmacology, Drug Therapy, Combination, Female, Genotype, HIV Infections virology, HIV Protease genetics, HIV Protease Inhibitors pharmacology, HIV Protease Inhibitors therapeutic use, HIV Reverse Transcriptase genetics, HIV-1 enzymology, HIV-1 genetics, HIV-1 physiology, Humans, Male, Middle Aged, Mutation, Phenotype, Predictive Value of Tests, Reverse Transcriptase Inhibitors pharmacology, Treatment Outcome, Viral Load, Anti-HIV Agents therapeutic use, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV-1 drug effects, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objective: To identify predictors of the virological response to antiretroviral therapy in patients in whom initial therapy has failed., Methods: The Narval trial was designed to compare phenotyping, genotyping and standard of care for the choice of antiretroviral therapy in patients in whom a protease inhibitor (PI)-containing regimen had failed. Virological success was defined as viral load below 200 copies/ml at week 12. Baseline variables including demographic, clinical and biological characteristics, HIV reverse transcriptase and protease mutations, the randomization arm, the drugs prescribed, as well as adherence to treatment and plasma concentrations of PIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) at week 12 were tested in the model. Variables that were significantly associated with virological success in univariate analysis were included in a logistic regression model., Results: Five-hundred-and-forty-one patients were randomized. Virological success at week 12 was obtained in 200 patients. In multivariate analysis, the following factors were significantly associated with virological success: prescription of efavirenz to NNRTI-naive patients (OR=4.37; 95% CI: 2.76-6.90), randomization to the genotyping arm (OR=2.13, 1.20-3.79), prescription of lamivudine (OR=1.69, 1.01-2.83) and prescription of abacavir to abacavir-naive patients (OR=1.66, 1.02-2.72). Factors significantly associated with virological failure were prescription of nelfinavir (OR=0.30, 0.13-0.68), a high baseline viral load (OR=0.37, 0.28-0.50), the presence of at least five PI mutations (OR=0.42, 0.26-0.66), the presence of at least three thymidine analogue mutations (OR=0.61, 0.39-0.97) and at least 30 months of prior PI exposure (OR=0.64, 0.41-0.99)., Conclusions: These results confirm that among heavily pretreated patients, prescription of efavirenz to NNRTI-naive patients is associated with a good virological response, while a high baseline viral load, a large number of PI mutations and nelfinavir prescription at baseline are associated with a poor virological response. Genotyping was found to be beneficial, while this was not the case for phenotyping. This work was presented at the XI International HIV Drug Resistance Workshop, Sevilla, Spain, July 3-6 2002 (Abstract N(o)133); and at the XIV International Conference on AIDS, Barcelona, Spain, July 7-11 2002 (Abstract N(o)ThOrB138).
- Published
- 2003
- Full Text
- View/download PDF
33. Clinically relevant interpretation of genotype for resistance to abacavir.
- Author
-
Brun-Vézinet F, Descamps D, Ruffault A, Masquelier B, Calvez V, Peytavin G, Telles F, Morand-Joubert L, Meynard JL, Vray M, and Costagliola D
- Subjects
- Genotype, HIV Infections virology, Humans, Multivariate Analysis, Mutation, RNA, Viral blood, Statistics, Nonparametric, Algorithms, Dideoxynucleosides therapeutic use, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV-1 genetics, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objective: To develop a stepwise methodology for the development and validation of clinically relevant genotypic score for resistance to antiretroviral drugs and to apply this approach to the genotypic resistance to abacavir., Methods: All patients having received abacavir during the Narval trial were included in this study. The impact of each nucleoside analogue resistance mutation on the virologic response to abacavir was studied in a univariate analysis. Mutations with a P value < 0.20 and those selected by abacavir were retained. According to the number of mutations three levels of resistance were defined. A multivariate analysis accounting for confonding variables assessed whether the genotypic score was an independent predictor of the response. The robustness of the score was analysed using the bootstrap resampling method., Results: In the 175 patients exposed to abacavir, the strongest association between the decrease in viral load and the number of mutations was observed with a set of six mutations at codons 41, 67, 210, 215, 74 and 184 of the reverse transcriptase gene. In patients with fewer than four mutations (no evidence of resistance) the median decrease in viral load was -1.64 log(10) copies/ml while it was -0.69 log(10) and -0.19 log(10) in those with four (possible resistance) and five or six (resistance) mutations respectively. In the multivariate analysis this score was an independent predictor of the response. The bootstrap analysis showed the robustness of the score., Conclusions: We developed a new strategy for the analysis of correlation between genotype profile at baseline and virologic response.
- Published
- 2003
- Full Text
- View/download PDF
34. 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
35. Low increase in serum lipids in patients receiving a combination of ritonavir, saquinavir and efavirenz.
- Author
-
Piketty C, Peytavin G, Trylezinski A, Gonzalez-Canali G, Castiel P, Weiss L, and Kazatchkine MD
- Subjects
- Alkynes, Benzoxazines, Blood Glucose drug effects, Cyclopropanes, Drug Therapy, Combination, Follow-Up Studies, HIV Infections blood, HIV Protease Inhibitors blood, Humans, Oxazines blood, Oxazines therapeutic use, Reverse Transcriptase Inhibitors blood, Ritonavir blood, Ritonavir therapeutic use, Saquinavir blood, Saquinavir therapeutic use, Cholesterol blood, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Triglycerides blood
- Published
- 2002
- Full Text
- View/download PDF
36. 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
37. Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial.
- Author
-
Meynard JL, Vray M, Morand-Joubert L, Race E, Descamps D, Peytavin G, Matheron S, Lamotte C, Guiramand S, Costagliola D, Brun-Vézinet F, Clavel F, and Girard PM
- Subjects
- Anti-HIV Agents pharmacokinetics, CD4 Lymphocyte Count, Drug Prescriptions, Drug Tolerance, Genotype, HIV Infections blood, HIV Infections immunology, HIV Infections virology, HIV Protease Inhibitors pharmacokinetics, HIV-1 genetics, Humans, Patient Compliance, Phenotype, Prospective Studies, Reverse Transcriptase Inhibitors pharmacokinetics, Treatment Failure, Viral Load, Anti-HIV Agents therapeutic use, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Objective: To assess the respective value of phenotype versus genotype versus standard of care for choosing antiretroviral therapy in patients failing protease inhibitor-containing regimens., Methods: Patients with plasma HIV-1 RNA exceeding 1000 copies/ml were randomly allocated to phenotyping, genotyping, or standard of care., Results: Five-hundred and forty-one patients were randomized, 190 to phenotyping, 192 to genotyping and 159 to standard of care. The baseline median CD4 cell count (280 x 106 cells/l), the plasma HIV-1 RNA level (4.3 log10 copies/ml), and the number of drugs previously received (n = 6) were similar in the three arms. More patients in the standard-of-care arm received at least three new drugs (55% versus 20% in the other arms; P < 0.001) and a regimen containing drugs from the three different classes. Plasma HIV-1 RNA was < 200 copies/ml at week 12 in 35% of patients in the phenotyping arm, 44% in the genotyping arm and 36% in the standard-of-care arm (phenotyping versus standard of care, P = 0.918; genotyping versus standard of care, P = 0.120). In a secondary analysis of 179 patients experiencing a first protease inhibitor failure, the percentage of patients achieving HIV-1 RNA < 200 copies/ml was significantly higher in the genotyping arm (65%) than in the phenotyping (45%) and the standard-of-care arms (45%) (genotyping versus standard of care, P = 0.022)., Conclusions: Overall, resistance assays did not demonstrate benefit over standard of care. In patients with the most limited protease inhibitor experience, a significant benefit was observed in the genotyping arm.
- Published
- 2002
- Full Text
- View/download PDF
38. Final analysis of the Trilège induction-maintenance trial: results at 18 months.
- Author
-
Flandre P, Raffi F, Descamps D, Calvez V, Peytavin G, Meiffredy V, Harel M, Hazebrouck S, Pialoux G, Aboulker JP, and Brun Vezinet F
- Subjects
- Adult, Anti-HIV Agents therapeutic use, Drug Administration Schedule, Drug Therapy, Combination, Female, Follow-Up Studies, HIV Infections virology, HIV Protease Inhibitors therapeutic use, HIV-1 genetics, Humans, Indinavir therapeutic use, Lamivudine therapeutic use, Male, Middle Aged, Multivariate Analysis, RNA, Viral blood, Reverse Transcriptase Inhibitors therapeutic use, Time Factors, Treatment Outcome, Viral Load, Zidovudine therapeutic use, Anti-HIV Agents administration & dosage, HIV Infections drug therapy, HIV Protease Inhibitors administration & dosage, HIV-1 drug effects, Indinavir administration & dosage, Lamivudine administration & dosage, Reverse Transcriptase Inhibitors administration & dosage, Zidovudine administration & dosage
- Abstract
Background: First results of Trilège demonstrated that the strategy of less intensive antiviral therapy is less effective than continuation of triple-drug therapy., Objective: To compare the final number of failures at month 18 and to study viral dynamics in patients experiencing a virological failure., Design: Longitudinal follow-up from a randomized controlled trial., Setting: Forty-three AIDS clinical-trial units., Patients: A total of 279 HIV-1 infected adults randomized in Trilège., Measurements: Analysis of recurrent values of HIV RNA > 500 copies/ml beyond time to virologic failure., Results: A total of 83 patients experienced virological failure by month 18; 10 in the zidovudine (ZDV) + lamivudine (3TC) + indinavir (IDV) arm, 46 in the ZDV + 3TC arm, and 27 in the ZDV + IDV arm, confirming previous results. Whatever the treatment ultimately received, 87% of patients had an HIV RNA < 500 copies/ml at month 18 with no statistical difference between randomized arms. Patients experiencing a failure in the triple-drug regimen had a greater tendency to maintain HIV RNA > 500 copies/ml beyond the time of virological failure than patients in both less intensive treatment groups who experienced failure. Lower levels of HIV RNA at failure and reinitiating of either the original triple-drug regimen or a new combination of nucleoside analogue reverse transcriptase inhibitors and protease inhibitors were associated with lower hazard ratios for developing recurrent HIV RNA > 500 copies/ml., Conclusion: Results confirmed the failure of a less intensive regimen to maintain patients with a viral suppression (HIV RNA < 500 copies/ml). Although there is a lower incidence of failure in the triple-drug regimen, randomization to a less intensive regimen of ZDV + 3TC or ZDV + IDV was not detrimental, as treatment modification, either to the original triple regimen, or a different regimen was successful.
- Published
- 2002
- Full Text
- View/download PDF
39. Evaluation of the Patient Medication Adherence Questionnaire as a tool for self-reported adherence assessment in HIV-infected patients on antiretroviral regimens.
- Author
-
Duong M, Piroth L, Grappin M, Forte F, Peytavin G, Buisson M, Chavanet P, and Portier H
- Subjects
- Adult, Drug Therapy, Combination, Female, HIV Infections psychology, HIV Protease Inhibitors pharmacokinetics, HIV-1 isolation & purification, HIV-1 physiology, Health Knowledge, Attitudes, Practice, Humans, Male, RNA, Viral blood, Surveys and Questionnaires, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Protease Inhibitors therapeutic use, Patient Compliance psychology, Reverse Transcriptase Inhibitors therapeutic use
- Abstract
Purpose: Adherence to antiretroviral medications is critically important for the success of therapy in patients treated for HIV infection. Patient self-report is a simple method to measure and explore adherence. Even though a variety of surveys have been developed to monitor self-reported adherence, there is no standardized instrument that may be used in routine clinical practice. The usefulness of the Patient Medication Adherence Questionnaire (PMAQ) was evaluated in HIV-infected patients on protease inhibitor (PI)-containing regimens., Method: Data from 149 patients were collected. Study participants completed the PMAQ and provided blood samples to measure plasma HIV-1 RNA concentrations and trough plasma levels of PI. Patients were considered adherent if they had a virologic response and/or had an adequate trough plasma level of PI., Results: A close relationship was found between patient reports of adherence during the previous 4 days and objective measures such as HIV RNA level and plasma levels of PI. Motivation with regard to antiretroviral treatment, confidence in personal skills, and an optimistic attitude to life were identified as important determinants of adherence. On the other hand, sociodemographic background, social support, alcohol and illicit drug use, bothersome symptoms, and depression were not associated with a lower medication adherence., Conclusion: Patients' psychological and behavioral factors are central in the acceptance and adherence to antiretroviral therapy. To improve the feasibility and the reproducibility of the PMAQ, we propose a revised form of the PMAQ, focusing on the variables identified as strong predictors of adherence.
- Published
- 2001
- Full Text
- View/download PDF
40. Nevirapine Use Is Associated with Higher Bone Mineral Density in HIV-1 Positive Subjects on Long-Term Antiretroviral Therapy
- Author
-
Couffignal, Camille, Kolta, Sami, Flamant, Martin, Cazanave, Charles, Haymann, Jean-Philippe, Mentre, France, Duval, Xavier, Leport, Catherine, Raffi, Francois, Chêne, G., Salamon, R., Moatti, J., Pierret, J., Spire, B., Brun-Vézinet, F., Fleury, H., Masquelier, B., Peytavin, G., Garraffo, R., Costagliola, D., Dellamonica, P., Katlama, C., Meyer, L., Salmon, D., Cuzin, L., Dupon, M., Le Moing, V., Marchou, B., May, T., Morlat, P., Rabaud, C., Waldner-Combernoux, A., Hardel, L., Reboud, P., Couffin-Cadiergues, S., Marchand, L., Assuied, A., Carrieri, P., Habak, S., Couturier, F., Jadand, C., Perrier, A., Préau, M., Protopopescu, C., Schmit, J.L., Chennebault, J.M., Faller, J.P., Magy-Bertrand, N., Chirouze, C., Humbert, P., Neau, D., Granier, P., Ansart, S., Verdon, R., Merrien, D., Chevojon, P., Sobel, A., Levy, Y., Piroth, L., Perronne, C., Froguel, E., Ceccaldi, J., Chidiac, C., Grégoire, V., Reynes, J., Fuzibet, J., Arsac, P., Bouvet, E., Bricaire, F., Monsonego, J., Girard, P.M., Guillevin, L., Herson, S., Molina, J.M., Pialoux, G., Sain, O., Sellier, P., Roblot, F., Bani-Sadr, F., Michelet, C., Lucht, F., Debord, C., Martin, T., de Jaureguiberry, J.P., Bernard, L., Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service des Maladies Infectieuses et Tropicales A [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Pharmacie de l'Hôpital Bichat, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des maladies infectieuses, Centre Hospitalier Universitaire de Nice (CHU Nice)-University Hospital, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Bell Labs (BELL), Lucent Technologies, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service de virologie et d'immunologie biologique, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Unité de Maladies Infectieuses et Tropicales [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Libourne, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Radiation Oncology, Université Catholique de Louvain = Catholic University of Louvain (UCL), GERES - Groupe d'Étude sur le Risque d'Exposition des Soignants aux agents infectieux - Research Group for the Prevention of Occupational Infections in Healthcare Workers [Paris, France], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), University Hospital and University Jean Monnet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Groupe d'Étude sur le Risque d'Exposition des Soignants aux agents infectieux (GERES), Cholley, Pascal, and Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière]
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Nevirapine ,nevirapine ,Immunology ,Cumulative Exposure ,HIV Infections ,03 medical and health sciences ,Absorptiometry, Photon ,0302 clinical medicine ,Bone Density ,Virology ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,030304 developmental biology ,Bone mineral ,0303 health sciences ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Incidence (epidemiology) ,HIV ,virus diseases ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,3. Good health ,Cross-Sectional Studies ,Infectious Diseases ,Cohort ,HIV-1 ,Coinfection ,Reverse Transcriptase Inhibitors ,Female ,bone mineral density ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Follow-Up Studies ,medicine.drug - Abstract
International audience; We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA
- Published
- 2020
41. Resistance profile and treatment outcomes in HIV-infected children at virological failure in Benin, West Africa.
- Author
-
Fofana, D B, Lambert-Niclot, S, d'Almeida, M, Zohoun-Guidigbi, L, Peytavin, G, Girard, P M, Lafia, B, Keke, R K, Soulie, C, Marcelin, A G, and Morand-Joubert, L
- Subjects
HIV-positive children ,THERAPEUTICS ,DRUG resistance ,PREVENTIVE medicine ,COMPARATIVE studies ,DRUG resistance in microorganisms ,GENETIC techniques ,HIV ,HIV infections ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,VIRAL load ,EVALUATION research ,HIGHLY active antiretroviral therapy ,TREATMENT effectiveness ,ANTI-HIV agents ,REVERSE transcriptase inhibitors ,CD4 lymphocyte count - Abstract
Background: In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations.Objectives: To assess the frequency and patterns of HIV drug resistance among children with virological ART failures.Methods: Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination.Results: Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations.Conclusions: Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
42. Therapeutic drug monitoring and drug-drug interactions involving antiretroviral drugs
- Author
-
Boffito, M., Acosta, E., Burger, D., Fletcher, C. V., Flexner, C., Garaffo, R., Gatti, G., Kurowski, M., CARLO FEDERICO PERNO, Peytavin, G., Regazzi, M., and Back, D.
- Subjects
Invasive mycoses and compromised host [N4i 2] ,Infectious diseases and international health [NCEBP 13] ,Cognitive neurosciences [UMCN 3.2] ,Anti-HIV Agents ,Practice Guidelines as Topic ,Poverty-related infectious diseases [N4i 3] ,Humans ,Reverse Transcriptase Inhibitors ,Drug Interactions ,HIV Infections ,Drug Monitoring ,Settore MED/07 - Microbiologia e Microbiologia Clinica - Abstract
Contains fulltext : 47437.pdf (Publisher’s version ) (Closed access) The consensus of current international guidelines for the treatment of HIV infection is that data on therapeutic drug monitoring (TDM) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (Pls) provide a framework for the implementation of TDM in certain defined scenarios in clinical practice. However, the utility of TDM is considered to be on an individual basis until more data are obtained from large clinical trials showing the benefit of TDM. In April 2004, a panel of experts met for the second time in Rome, Italy. This was following the inaugural meeting in Perugia, Italy, in October 2000, which resulted in the manuscript published in AIDS 2002, 16(Suppl 1):S5-S37. The objectives of this second meeting were to review and update the numerous questions surrounding TDM of antiretroviral drugs and discuss the clinical utility, current concerns and future prospects of drug concentration monitoring in the care of HIV-1-infected individuals. A major focus of the meeting was to discuss and critically analyse recent and precedent clinical drug-drug interaction data to provide a clear framework of the pharmacological basis of how one drug may impact the disposition of another. This report, which has been updated to include material published or presented at international conferences up to the end of December 2004, reviews recent pivotal pharmacokinetic interaction data and provides advice to clinical care providers on how some drug-drug interactions may be prevented, avoided or managed, and, when data are available, on what dose adjustments and interventions should be performed.
- Published
- 2005
43. Efficacy and tolerability of combined antiretroviral treatment with bictegravir/emtricitabine/tenofovir alafenamide initiated at the time of primary HIV infection.
- Author
-
Bachelard, A, Isernia, V, Vallois, D, Gac, S Le, Chalal, L, Landman, R, Damond, F, Descamps, D, Yazdanpanah, Y, Peytavin, G, Ghosn, J, and Le Gac, S
- Subjects
ANTIRETROVIRAL agents ,TENOFOVIR ,INFECTION ,EMTRICITABINE ,HIV infections ,REVERSE transcriptase inhibitors ,SYPHILIS - Published
- 2021
- Full Text
- View/download PDF
44. Low-dose ritonavir-boosted darunavir in virologically suppressed HIV-1-infected adults: an open-label trial (ANRS 165 Darulight)
- Author
-
Jean-Michel, Molina, Sebastien, Gallien, Marie-Laure, Chaix, El Mountacer, El Abbassi, Isabelle, Madelaine, Christine, Katlama, Nadia, Valin, Pierre, Delobel, Kristell, Desseaux, Gilles, Peytavin, Juliette, Saillard, François, Raffi, Sylvie, Chevret, S, Gibowski, Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Laboratoire de Virologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistiques et information médicale [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Pharmacologie [AP-HP Hôpital Bichat - Claude Bernard], AP-HP - Hôpital Bichat - Claude Bernard [Paris], ANRS France Recherche Nord & sud Sida-hiv hépatites, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département des Maladies Infectieuses [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ANRS 165 Darulight Study Group : Ponscarme D, Lascoux C, Girard PM, Rami A, Yazdanpanah Y, Simon A, Tubiana R, Duvivier C, Jeantils V, Loreillard D, Poizot-Martin I, Bernard L, Gras G, Allavena C, Bernaud C, Bouchez S, Hall N, Reliquet V, Raffi F, De Truchis P, Charreau I, Bocquet L, Lemoing V, Point G, Molina JM, Chevret S, El Abbassi EM, Gallien S, Tattevin P, Gras G, Chaix ML, Peytavin G, Saillard J, Couffin-Cadiergues S, Madelaine I, Diallo A, Gibowski S., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Dupuis, Christine
- Subjects
Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,HIV Infections ,Emtricitabine ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Abacavir ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Darunavir ,Pharmacology ,Ritonavir ,business.industry ,virus diseases ,Lamivudine ,HIV Protease Inhibitors ,Middle Aged ,Viral Load ,030112 virology ,3. Good health ,Discontinuation ,Regimen ,Treatment Outcome ,Infectious Diseases ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,RNA, Viral ,Reverse Transcriptase Inhibitors ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Drug Therapy, Combination ,Female ,business ,Viral load ,medicine.drug - Abstract
International audience; Objectives:To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs.Design:A multicentre, Phase II, non-comparative, single-arm, open-label study.Setting:Tertiary care hospitals in France.Subjects:One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs.Primary outcome measure:Proportion of patients with treatment success: plasma HIV RNA level ≤50 copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis.Results:At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation.Conclusions:In HIV-infected patients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.
- Published
- 2018
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.