Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women

The purpose of this research study is to evaluate the effect of body changes in pregnancy on doravirine concentrations, to determine what dose of doravirine should be used. Study participants will remain on their normal antiretroviral medications (ARVs) while participating in this study as prescribed by their regular clinic provider. Study participants will come to the research clinic for three sampling visits throughout their time as a participant. Study participants will only take one dose of doravirine during each sampling visit, which will occur during the 2nd and 3rd trimesters, as well as after their baby is delivered. This study was designed intentionally to not give a dose of doravirine in the first trimester when there is the greatest chance for all drugs to potentially cause injury to the baby. Study participants that choose to participate in this study may be enrolled for up to 10 months depending on the length of their pregnancy and how the visits are scheduled.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Pregnancy Related
• Intervention / Treatment: Drug: Doravirine

Detailed Description

Antiretroviral (ARV) medications are used to treat infection with human immunodeficiency virus (HIV). During pregnancy, ARV therapy keeps women healthy and decreases the spread of HIV to their babies (<1-2%).

Many changes occur in the body during pregnancy, which can alter the concentrations of drug in the body. Doravirine (DOR) is a Food and Drug Administration (FDA) approved ARV, but the extent to which the drug concentrations of doravirine change during pregnancy is unknown. Because these changes are unknown, DOR has not been approved by the FDA for use among pregnant women; however, the FDA has given the researchers permission to use it in this study Pregnant women are often excluded from clinical trials, so it can take several years after a drug gets approved before contemporary ARV is available to them.

The purpose of this research study is to evaluate the effect of body changes in pregnancy on doravirine concentrations, to determine what dose of doravirine should be used. Study participants will remain on their normal antiretroviral medications (ARVs) while participating in this study as prescribed by their regular clinic provider. Study participants will come to the research clinic for three sampling visits throughout their time as a participant. Study participants will only take one dose of doravirine during each sampling visit, which will occur during the 2nd and 3rd trimesters, as well as after their baby is delivered. This study was designed intentionally to not give a dose of doravirine in the first trimester when there is the greatest chance for all drugs to potentially cause injury to the baby. Study participants that choose to participate in this study may be enrolled for up to 10 months depending on the length of their pregnancy and how the visits are scheduled.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women living with Human Immunodeficiency Virus (HIV) ≥18 years of age
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial.
• On stable combination Antiretroviral Therapy (cART) for at least 30 days prior to enrollment
• Plasma HIV RNA < 50 copies/mL within 90 days prior to enrollment

• Ability and willingness of participant to not change their cART regimen to avoid any confounding of pharmacokinetic (PK) parameters.

  o Note: Women who change cART regimens will be replaced.

• Aspartate aminotransferase and alanine aminotransferase < 3x Upper Limit of Normal (ULN)
• Hemoglobin lower than Division of AIDs (Acquired Immunodeficiency Syndrome) (DAIDs) Grade 2 (9.0 g/dL)

Exclusion Criteria:

• Women with multiple gestation, active opportunistic infections, present obstetrical complications that would deem them unsuitable for study participation, or evidence of fetal anomalies in present pregnancy will be excluded.
• Women with severe renal impairment, end stage renal disease, undergoing dialysis, or severe hepatic impairment (Child-Pugh C)
• Women with a significant illness/condition at the time of enrollment that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or assessment of safety.
• Women with pregnancies that have become complicated are excluded for safety reasons.
• Active hepatitis C (HCV) infection as defined by anti-hepatitis C virus serology (as determined by multi-antigen EIA) and detectable HCV RNA.
• Clinically significant labs greater than Grade 2 on the NIH Division of AIDs Table for Grading the Severity of Adult and Pediatric Adverse events
• Receiving CYP3A inducers including carbamazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, or St. John's wort or other drugs, including antiretrovirals, that influence drug concentration or alter pharmacokinetic profiles (atazanavir, maraviroc, darunavir, norvir, efavirenz, tipranavir)
• Receiving moderate to strong cytochrome p450 3A (CYP3A) inhibitors including clarithromycin, boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir, posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, grapefruit juice, idelalisib, nefazodone, and nelfinavir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doravirine; 100mg doravirine given by mouth once at each sampling visit.	Drug: Doravirine; 100mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Doraviraine During Pregnancy	To describe single-dose total and protein-unbound Cmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum	Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Doravirine During Pregnancy	To describe single-dose total and protein-unbound Tmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum	Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Concentration of Doravirine at 12 Hours (C12) Postdose Doravirine During Pregnancy	To describe single-dose total and protein-unbound C12h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum	Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Concentration of Doravirine at 24 Hours (C24) Postdose Doravirine During Pregnancy	To describe single-dose total and protein-unbound C24 of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum	Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Area Under the Concentration-Time Curve From Zero to 24 Hours After Dosing (AUC0-24) of Doravirine During Pregnancy	To describe single-dose total and protein-unbound AUC of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum	Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events Reported After Single Doses of Doravirine in Pregnant Participants	To evaluate the number of Adverse Events reported after single doses of doravirine in pregnant participants living with HIV	From enrollment visit to follow-up visit, an average of 10 months

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Angela Kashuba, PharmD, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): March 27, 2025
• Study Completion (Actual): April 8, 2025

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 25, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; doravirine
• Other Study ID Numbers: 20-0052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: Beginning 9 to 36 months following publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No