Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda
© 2013, The American College of Clinical Pharmacology..
Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well-nourished controls (P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% (P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure (P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
Journal of clinical pharmacology - 54(2014), 2 vom: 15. Feb., Seite 121-32 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bartelink, Imke H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.09.2015 Date Revised 07.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jcph.167 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM23088895X |
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| 100 | 1 | |a Bartelink, Imke H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV-infected pregnant and breastfeeding women in Tororo, Uganda |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Completed 18.09.2015 | ||
| 500 | |a Date Revised 07.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2013, The American College of Clinical Pharmacology. | ||
| 520 | |a Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics (PK), adherence and response. We sought to quantify and characterize the PK of lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante-partum/post-partum single dried blood spot samples DBS and 43 post-partum hair samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and 53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan participants were severely food insecure, 26% lost weight ante-partum, and median BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished (pregnant) women and healthy Ugandans established prior information. Overall, drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well-nourished controls (P < 0.001), attributable to decreased bioavailability. Pregnancy increased LPV/r clearance 68% (P < 0.001), whereas EFV clearance remained unchanged. Hair concentrations correlated with plasma-exposure (P < 0.001), explaining 29% PK-variability. In conclusion, pregnancy and food insecurity were associated with lower ART exposures in this cohort of predominantly underweight women, compared to well-nourished women. Much variability in plasma-exposure was quantified using hair concentrations. Addressing malnutrition as well as ART-PK in this setting should be a priority | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a clinical research (CRE) | |
| 650 | 4 | |a infectious diseases (INF) | |
| 650 | 4 | |a pharmacodynamics (PDY) | |
| 650 | 4 | |a pharmacokinetics and drug metabolism | |
| 650 | 4 | |a pharmacology (PHA) | |
| 650 | 7 | |a Alkynes |2 NLM | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Benzoxazines |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a Lopinavir |2 NLM | |
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| 650 | 7 | |a efavirenz |2 NLM | |
| 650 | 7 | |a JE6H2O27P8 |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Savic, Rada M |e verfasserin |4 aut | |
| 700 | 1 | |a Mwesigwa, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Achan, Jane |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Plenty, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Charlebois, Edwin |e verfasserin |4 aut | |
| 700 | 1 | |a Kamya, Moses |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Sera L |e verfasserin |4 aut | |
| 700 | 1 | |a Gandhi, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Havlir, Diane |e verfasserin |4 aut | |
| 700 | 1 | |a Cohan, Deborah |e verfasserin |4 aut | |
| 700 | 1 | |a Aweeka, Francesca |e verfasserin |4 aut | |
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