Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum

IMPAACT P1026s Protocol Team

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Concentrations of antiretrovirals in the genital tract play a key role in preexposure prophylaxis. This study aims to describe rilpivirine (Edurant) concentrations in the genital tract in pregnant and postpartum women. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly aspirated cervicovaginal fluid (CVF) samples were collected at 4 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL). RESULTS: A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/mL (23-121) in CVF and 92 ng/mL (49-147) in plasma. The CVF to plasma AUC(0-4) ratios were significantly higher in the second (0.90, 90% CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90% CI: 0.19 to 0.87). Three of 189 (1.6%) plasma samples in 2 women were below the LLQ and the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6%) were below LLQ in 13 participants. No major safety concerns were noted. CONCLUSIONS: Rilpivirine concentrations were higher in the CVF during pregnancy compared with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.

Original languageEnglish (US)
Pages (from-to)308-313
Number of pages6
JournalJournal of acquired immune deficiency syndromes (1999)
Volume78
Issue number3
DOIs
StatePublished - Jul 1 2018

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Rilpivirine
Postpartum Period
Pregnancy
Third Pregnancy Trimester
Clinical Protocols
Pregnant Women
Pharmacokinetics
HIV
Peripartum Period
Second Pregnancy Trimester
Tandem Mass Spectrometry
Liquid Chromatography
Area Under Curve
Acquired Immunodeficiency Syndrome
High Pressure Liquid Chromatography
Mothers
Clinical Trials
Prospective Studies
Pediatrics
Safety

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum. / IMPAACT P1026s Protocol Team.

In: Journal of acquired immune deficiency syndromes (1999), Vol. 78, No. 3, 01.07.2018, p. 308-313.

Research output: Contribution to journalArticle

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title = "Rilpivirine Plasma and Cervicovaginal Concentrations in Women During Pregnancy and Postpartum",
abstract = "BACKGROUND: Concentrations of antiretrovirals in the genital tract play a key role in preexposure prophylaxis. This study aims to describe rilpivirine (Edurant) concentrations in the genital tract in pregnant and postpartum women. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly aspirated cervicovaginal fluid (CVF) samples were collected at 4 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL). RESULTS: A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/mL (23-121) in CVF and 92 ng/mL (49-147) in plasma. The CVF to plasma AUC(0-4) ratios were significantly higher in the second (0.90, 90{\%} CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90{\%} CI: 0.19 to 0.87). Three of 189 (1.6{\%}) plasma samples in 2 women were below the LLQ and the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6{\%}) were below LLQ in 13 participants. No major safety concerns were noted. CONCLUSIONS: Rilpivirine concentrations were higher in the CVF during pregnancy compared with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.",
author = "{IMPAACT P1026s Protocol Team} and Eke, {Ahizechukwu C.} and Nahida Chakhtoura and Angela Kashuba and Best, {Brookie M.} and Craig Sykes and Jiajia Wang and Stek, {Alice M.} and Elizabeth Smith and Samantha Calabrese and Capparelli, {Edmund V.} and Mark Mirochnick",
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AU - IMPAACT P1026s Protocol Team

AU - Eke, Ahizechukwu C.

AU - Chakhtoura, Nahida

AU - Kashuba, Angela

AU - Best, Brookie M.

AU - Sykes, Craig

AU - Wang, Jiajia

AU - Stek, Alice M.

AU - Smith, Elizabeth

AU - Calabrese, Samantha

AU - Capparelli, Edmund V.

AU - Mirochnick, Mark

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N2 - BACKGROUND: Concentrations of antiretrovirals in the genital tract play a key role in preexposure prophylaxis. This study aims to describe rilpivirine (Edurant) concentrations in the genital tract in pregnant and postpartum women. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly aspirated cervicovaginal fluid (CVF) samples were collected at 4 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL). RESULTS: A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/mL (23-121) in CVF and 92 ng/mL (49-147) in plasma. The CVF to plasma AUC(0-4) ratios were significantly higher in the second (0.90, 90% CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90% CI: 0.19 to 0.87). Three of 189 (1.6%) plasma samples in 2 women were below the LLQ and the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6%) were below LLQ in 13 participants. No major safety concerns were noted. CONCLUSIONS: Rilpivirine concentrations were higher in the CVF during pregnancy compared with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.

AB - BACKGROUND: Concentrations of antiretrovirals in the genital tract play a key role in preexposure prophylaxis. This study aims to describe rilpivirine (Edurant) concentrations in the genital tract in pregnant and postpartum women. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trials Protocol P1026s is an ongoing, prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women that include a cohort receiving rilpivirine combination regimen. Intensive pharmacokinetics evaluations were performed at steady state during the second and third trimester, and postpartum. Plasma and directly aspirated cervicovaginal fluid (CVF) samples were collected at 4 time points around an observed dose and measured using high-performance liquid chromatography with ultraviolet detection, [plasma; lower limit of quantification (LLQ) = 10 ng/mL] or liquid chromatography-tandem mass spectrometry (CVF; LLQ = 1 ng/mL). RESULTS: A total of 24 women were included in the analysis. For all time points combined, median (interquartile range) rilpivirine concentrations were 70 ng/mL (23-121) in CVF and 92 ng/mL (49-147) in plasma. The CVF to plasma AUC(0-4) ratios were significantly higher in the second (0.90, 90% CI: 0.61 to 1.46) and third trimesters of pregnancy compared with postpartum (0.40, 90% CI: 0.19 to 0.87). Three of 189 (1.6%) plasma samples in 2 women were below the LLQ and the corresponding CVF concentrations. Seventeen additional CVF concentrations (10.6%) were below LLQ in 13 participants. No major safety concerns were noted. CONCLUSIONS: Rilpivirine concentrations were higher in the CVF during pregnancy compared with postpartum. CVF Rilpivirine is likely to achieve inhibitory concentrations effective for preventing peripartum HIV transmission.

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