Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals
BACKGROUND: We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads.
SETTINGS: Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals.
METHODS: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.
RESULTS: Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine Cmax, Ctrough, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded.
CONCLUSIONS: rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
HIV clinical trials - 19(2018), 1 vom: 02. Feb., Seite 31-37 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jackson, Akil [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.01.2019 Date Revised 04.01.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/15284336.2017.1408928 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM278547702 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM278547702 | ||
| 003 | DE-627 | ||
| 005 | 20231225020839.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/15284336.2017.1408928 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0928.xml |
| 035 | |a (DE-627)NLM278547702 | ||
| 035 | |a (NLM)29189101 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jackson, Akil |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.01.2019 | ||
| 500 | |a Date Revised 04.01.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads | ||
| 520 | |a SETTINGS: Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals | ||
| 520 | |a METHODS: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval | ||
| 520 | |a RESULTS: Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine Cmax, Ctrough, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded | ||
| 520 | |a CONCLUSIONS: rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Darunavir | |
| 650 | 4 | |a Dual antiretroviral therapy | |
| 650 | 4 | |a HIV antiviral pharmacology | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Rilpivirine | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a HIV Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Rilpivirine |2 NLM | |
| 650 | 7 | |a FI96A8X663 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 650 | 7 | |a Darunavir |2 NLM | |
| 650 | 7 | |a YO603Y8113 |2 NLM | |
| 700 | 1 | |a Else, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Higgs, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Karolia, Zeenat |e verfasserin |4 aut | |
| 700 | 1 | |a Khoo, Saye |e verfasserin |4 aut | |
| 700 | 1 | |a Back, David |e verfasserin |4 aut | |
| 700 | 1 | |a Devitt, Emma |e verfasserin |4 aut | |
| 700 | 1 | |a Pozniak, Anton |e verfasserin |4 aut | |
| 700 | 1 | |a Boffito, Marta |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t HIV clinical trials |d 2000 |g 19(2018), 1 vom: 02. Feb., Seite 31-37 |w (DE-627)NLM114850178 |x 1528-4336 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2018 |g number:1 |g day:02 |g month:02 |g pages:31-37 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/15284336.2017.1408928 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2018 |e 1 |b 02 |c 02 |h 31-37 | ||