Doravirine Dose Optimisation in Pregnancy (DoraDO)

A randomised, open label, controlled PK standard of care vs doravirine plus 2 nucleoside reverse transcriptase inhibitors backbone in pregnant women initiating combination antiretroviral therapy in the second trimester of pregnancy.

Study Overview

• Status: Recruiting
• Conditions: HIV
• Intervention / Treatment: Drug: Doravirine; Drug: Dolutegravir

Detailed Description

Women diagnosed HIV positive in the second trimester of pregnancy in South Africa will be enrolled and randomised 1:1 to receive standard of care or doravirine plus 2 NRTI backbone. Participants will receive study treatment until delivery and up to 28 weeks postpartum, with a maximum total of 14 months of study treatment. Given the high prevalence of NNRTI resistance, alternative ARV treatment options are essential. Doravirine is licenced for the treatment of HIV-1 in adults in North America and Europe. Whilst the efficacy and safety of doravirine has been established in non-pregnant adults, there are no adequate human data available to establish whether DOR poses a risk to pregnancy outcomes. It is important to have data on the safety and pharmacokinetics of the drug during pregnancy and in particularly the third trimester of pregnancy in order to support its use. The hypothesis for this study is that pregnancy influences the pharmacokinetics of doravirine when initiated in the second trimester.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Helen Reynolds; Phone Number: + 44 151 794 5553; Email: dorado@liverpool.ac.uk

Study Locations

• South Africa
  • Cape Town, South Africa
    • Recruiting
    • Desmond Tutu Health Foundation
    • Contact: Alicia James; Email: info@hiv-research.org.za
    • Principal Investigator: Lauren Jennings
    • Sub-Investigator: Catherine Orrell

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Women ≥ 18 years old
• Ability to give informed consent prior to participation
• Willing and able to comply with all study requirements
• HIV positive
• Pregnant (initiating cART ≥ 12 weeks and < 26 weeks gestation)
• Intention to breastfeed postpartum

Exclusion Criteria:

• Received any cART in preceding 6 months
• Chronic hepatitis B (HBV) infection with clinical evidence of transaminitis
• Elevations in serum levels of alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN) or ALT > 3xULN and bilirubin >2xULN (with > 35 % direct bilirubin)
• Previous documented failure of an NNRTI-containing cART regimen
• Previous history of hypersensitivity to any ARV
• Concomitant medication which are inducers of SoC and DOR metabolism (e.g. rifampicin, anti-epileptic agents, rifabutin, St John's Wort, mitotane, enzalutamide, lumacaftor). Contraindicated medications can be found on Liverpool Drug Interactions website (hiv-druginteractions.org)
• Participants with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption cannot take DOR as the tablet contains lactose monohydrate
• Clinical depression or clinical judgment suggests increased risk of suicidality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delstrigo; doravirine/lamivudine/tenofovir disoproxil 100 mg/ 300 mg/ 245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study	Drug: Doravirine; Fixed dose combination of doravirine, lamivudine and tenofovir disoproxil; Other Names: Delstrigo
Active Comparator: Standard of care; dolutegravir/lamivudine/tenofovir disoproxil 50 mg/300 mg/245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study	Drug: Dolutegravir; Fixed dose combination of dolutegravir, lamivudine and tenofovir disoproxil; Other Names: TLD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - AUC	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Cmax of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - Cmax	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Cmin of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - Cmin	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
CL/F of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - CL/F	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the number of treatment related adverse events by DAIDS v2.1	Safety and tolerability of doravirine in mothers and neonates	Until study completion, a maximum of 13 months
To determine the concentration of doravirine in breastmilk, in breastfed infants, in genital tract, cord blood	Pharmacokinetics of doravirine in various compartments	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
To assess maternal viral load responses	Viral load assessment	Delivery and 6 months postpartum
To determine infant transmissions in the first 6 months of life using HIV viral load	Assessment of perinatal transmission using HIV viral load	Delivery until 6 months postpartum
To assess the prevalence or emergence of HIV drug resistance by determining HIV mutations	Assessment of drug resistance tests	Until study completion, a maximum of 13 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral dynamics in the genital tract of mothers	Assessment of viral load in the genital tract	Baseline and 32 to 36 weeks gestation
PK in the genital tract of mothers	Assessment of drug concentrations in the genital tract	Baseline and 32 to 36 weeks gestation
PK of DOR in breastmilk, breastfed infants and in the genital tract	Assessment of drug concentrations in non-plasma compartments	Delivery, 6 weeks postpartum and 24 weeks postpartum
Prevalence or emergence of HIV drug resistance by determining HIV mutations	Assessment of drug resistance tests	Baseline to 24 weeks postpartum

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: Liverpool School of Tropical Medicine; Desmond Tutu Health Foundation
• Investigators: Principal Investigator: Saye Khoo, University of Liverpool

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: November 18, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy
• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; dolutegravir; doravirine
• Other Study ID Numbers: UoL001707

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators will consider all reasonable requests by health-care providers, investigators, and researchers to provide anonymised data to address specific scientific or clinical objectives. The investigators are committed to reviewing requests from researchers for access to clinical trial protocols, de-identified patient-level clinical trial data, and study-level clinical trial data. Data will be assigned a DOI through deposition in the University of Liverpool Research Data Catalogue (rdm@liverpool.ac.uk) and shared under a Data Transfer agreement (or equivalent e.g. as part of a research collaboration agreement or confidentiality disclosure agreement).
• IPD Sharing Time Frame: After study analysis has completed and manuscript is published for at least 5 years afterwards.
• IPD Sharing Access Criteria: By reasonable request to the investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No