Estudio primario

No clasificado

Año 2016
Registro de estudios clinicaltrials.gov
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This is a switch study to assess the non-inferiority (in terms of efficacy and safety) of darunavir (boosted with ritonavir, DRV/r 400mg/100mg daily) when compared with lopinavir (boosted with ritonavir, LPV/r total dose 800mg/200mg daily), in combination with a nucleoside backbone, administered as a second line therapy in HIV positive individuals.

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Estudio primario

No clasificado

Año 2019
Revista Antiviral therapy
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BACKGROUND:

Physiological changes during pregnancy can have a significant impact on antiretroviral pharmacokinetics (PK), which may result in reduced drug efficacy. Here we describe the PK of darunavir/ritonavir (DRV/r) 800/100 once daily in a cohort of pregnant women undergoing routine therapeutic drug monitoring (TDM) as well as transplacental passage of DRV by measuring and comparing cord blood and maternal blood samples at delivery.

METHODS:

Pregnant HIV-positive women received DRV/r as part of routine pre-natal care. Demographic and clinical data were collected. DRV plasma concentrations [DRV] were determined in the first (T1), second (T2) and third (T3) trimester and at postpartum (PP). The target concentration was 550 ng/ml. Where possible, paired maternal and cord blood samples were taken at delivery.

RESULTS:

A total of 33 women were enrolled. Samples were taken 14-20 h post-dose and measured concentrations were extrapolated to 24 h post-dose. At the time nearest to delivery, all but four had undetectable plasma viral loads (pVL). [DRV] were determined in 1 (T1); 14 (T2); 32 (T3) and 29 (PP). 1 sample was <550 ng/ml at T2, 6 at T3 and 3 at PP. [DRV] were significantly lower at T2/T3 relative to PP.

CONCLUSIONS:

[DRV] in T2 and T3 were 36-55% when compared with PP. However, DRV PK in pregnancy were not associated with a lack of virological suppression at delivery as of the 33 patients enrolled in this study, 31 had no HIV transmission from mother to child. Data regarding two candidates were not available as they delivered in a separate health-care facility.

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Estudio primario

No clasificado

Año 2011
Autores Janssen Cilag
Registro de estudios EU Clinical Trials Register
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INTERVENTION:

Trade Name: Prezista Product Name: TMC114 Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

Darunavir CAS Number: 635728‐49‐3 Other descriptive name: DARUNAVIR ETHANOLATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ Trade Name: Norvir Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

RITONAVIR CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Kaletra Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

LOPINAVIR CAS Number: 192725‐17‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed

INN:

RITONAVIR CAS Number: 155213‐67‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Trade Name: Retrovir Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

ZIDOVUDINE CAS Number: 30516‐87‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Viread Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

TENOFOVIR DISOPROXIL FUMARATE CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 300‐ Trade Name: Sustiva Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

EFAVIRENZ CAS Number: 154598‐52‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600‐ Trade Name: Retrovir Pharmaceutical Form: Capsule, hard INN or Proposed

INN:

ZIDOVUDINE CAS Number: 30516‐87‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ Trade Name: Truvada Pharmaceutical Form: Film‐coated tablet INN or Proposed

INN:

EMTRICITABINE CAS Number: 143491‐57‐0 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed

INN:

TENOFOVIR DISOPROXIL FUMARATE CAS Number: 202138‐50‐9 Concentration unit: mg milligram(s) Concentration type:

CONDITION:

HIV postexposure prophylaxis ; MedDRA version: 14.1 Level: PT Classification code 10054925 Term: Prophylaxis against HIV infection System Organ Class: 10042613 ‐ Surgical and medical procedures Therapeutic area: Body processes [G] ‐ Immune system processes [G12]

SECONDARY OUTCOME:

Secondary end point(s): ‐ to evaluate: ; • Tolerability and safety of HIV PEP. ; • Patient reported outcome (PRO) assessment of subject wellbeing and HIV PEP tolerability, as calculated from subject responses to SDS (Sheehan Disability Scale) questionnaire. ; Timepoint(s) of evaluation of this end point: 21 month

INCLUSION CRITERIA:

Potential subjects must satisfy all of the following criteria to be enrolled in the study: • Man or woman greater than 18 years of age. • Occupational injury or non ocupational injury with documented HIV exposure, or potential for HIV exposure. • Indication for HIV PEP, as determined by the treating physician and/or the investigator. • If standard of care HIV PEP was initiated prior to screening, this should have occurred no more than 72 hours after injury and no more than 36 hours before screening. • If standard of care HIV PEP is to be initiated after screening, this should occur no more than 72 hours after injury. • Women must be: • postmenopausal (for at least 2 years), • surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), • abstinent (at the discretion of the investigator/per local regulations), or • if sexually active, be practicing a highly

PRIMARY OUTCOME:

Main Objective: To assess the rate of early discontinuation from randomized HIV PEP for any reason other than confirmation of the negative HIV infection status of the index person in subjects receiving HIV PEP for at least 28 days and maximum 30 days. Primary end point(s): ‐ to assess the rate of early discontinuation from randomized HIV PEP for any reason other than confirmation of the negative HIV infection status of the index person in subjects receiving HIV PEP for at least 28 days and maximum 30 days; Secondary Objective: To evaluate:; • Tolerability and safety of HIV PEP.; • Patient reported outcome (PRO) assessment of functional impairment in conjunction with HIV PEP in 3 inter‐related domains (work, social life, and family life), as calculated from subject responses to the Sheehan Disability Scale (SDS) questionnaire.; Timepoint(s) of evaluation of this end point: 21 month

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Estudio primario

No clasificado

Año 2017
Autores Kirby Institute
Registro de estudios clinicaltrials.gov
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D²EFT is a randomised, open-label study in HIV-1 infected patients failing first-line antiretroviral therapy (ART). The study compares 2 regimens of second-line ART (dolutegravir and darunavir pharmaco-enhanced with ritonavir and dolutegravir and 2 prespecified NRTIs) with the WHO recommended regimen of 2NRTIs plus a ritonavir-boosted PI (Standard of Care (SOC)). 1,010 participants from 14 predominantly low-middle income countries will be followed for 96 weeks with the primary endpoint at week 48. The design is based on the hypothesis that one or both of the new regimens will be non-inferior to SOC in terms of virologic control while being easier to take, economically viable and affording simplification of treatment programs.

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Estudio primario

No clasificado

Año 2008
Autores Curran, A , Ribera Pascuet, E
Revista Enfermedades infecciosas y microbiologia clinica
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Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatment at 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non‐inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2‐16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2‐17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation in the protease, with these differences increasing as the number of these mutations increased. In patients with virological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.

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Estudio primario

No clasificado

Año 2014
Autores Fundacion SEIMC-GESIDA
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This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.

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Estudio primario

No clasificado

Año 2020
Revista Journal of acquired immune deficiency syndromes (1999)
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BACKGROUND:

This study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.

METHODS:

Darunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2-3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.

RESULTS:

Twenty-four women were included in the analysis. Darunavir AUC0-12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44-0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55-0.73); P = <0.001] compared with postpartum. Darunavir apparent clearance was higher during the second [GMR 1.77 (IQR 1.24-2.51); P = 0.039] and third trimesters [GMR 2.01 (IQR 1.17-2.35); P = <0.001] compared with postpartum. Similarly, ritonavir AUC0-12 was lower during the third trimester [GMR 0.65 (IQR 0.52-0.82); P = 0.007] compared with postpartum, whereas its apparent clearance was higher during the third trimester [GMR 1.53 (IQR 1.22-1.92); P = 0.008] compared with postpartum. No major drug-related safety concerns were noted.

CONCLUSIONS:

Increasing darunavir dose to 800 mg BID failed to significantly increase darunavir exposure compared with 600 mg BID. Other strategies, such as increasing the ritonavir dose should be investigated.

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Estudio primario

No clasificado

Año 2008
Autores Estrada, V , Fuster, M
Revista Enfermedades infecciosas y microbiologia clinica
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The ARTEMIS study compared the efficacy of darunavir/ritonavir at once‐daily doses of 800/100 mg versus once‐ or twice‐daily doses of lopinavir/ritonavir, together with 300 mg of tenofovir and 200 mg of emtricitabine, both in once‐daily doses, in treatment‐naive patients. The results at 48 weeks show that darunavir/ritonavir is not inferior to lopinavir/ritonavir; the increase in CD4 count observed with both regimens was similar. Darunavir/ritonavir was superior to lopinavir/ritonavir in patients with high viral loads (>100,000 copies/mL). The use of darunavir/ritonavir was associated with a lower proportion of grades 2‐4 adverse effects, especially gastrointestinal effects such as diarrhea and with a lower frequency of lipidic adverse effects, such as increased triglyceride and total cholesterol levels. Once‐daily darunavir/ritonavir may be an option in first‐line antiretroviral therapy, with the added advantage of a reduced dose of ritonavir and high efficacy in patients with elevated viral loads.

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Estudio primario

No clasificado

Año 2018
Autores Makerere University
Registro de estudios clinicaltrials.gov
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This study will evaluate the pharmacokinetic properties of rilpivirine and darunavir when used in combination with etonogestrel

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Estudio primario

No clasificado

Año 2011
Registro de estudios clinicaltrials.gov
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This is a clinical trial to characterize drug interactions between silimarine and the protease inhibitor darunavir/ritonavir.

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