Doravirine for HIV in Pregnancy

Overseen By Amanda Poliseno, BS

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Must be taking: Antiretrovirals

Must not be taking: CYP3A inducers, CYP3A inhibitors

Disqualifiers: Multiple gestation, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 10 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how pregnancy affects the levels of doravirine, a medication used to treat HIV, in the body. Participants will take doravirine once during each of three visits: in the second trimester, third trimester, and after delivery. The trial seeks to determine the best dose of doravirine during pregnancy. Women living with HIV who have been on stable antiretroviral therapy (ART) for at least 30 days may be suitable for this study. As a Phase 1 trial, this research focuses on how doravirine works in pregnant women, offering participants the opportunity to contribute to vital early-stage research.

Will I have to stop taking my current medications?

Participants will not have to stop taking their current antiretroviral medications, as they are required to stay on their existing treatment plan during the study. However, if you are taking certain medications that affect drug concentration, you may not be eligible to participate.

Is there any evidence suggesting that doravirine is likely to be safe for humans?

Research has shown that doravirine is generally safe for adults and is used to treat HIV. However, insufficient information exists regarding the risks of birth defects or other pregnancy-related issues.

A registry tracks pregnancy outcomes for those who have taken doravirine, gathering more information about its safety during pregnancy. Importantly, this study avoids using the drug in the first trimester, when the risk to the baby is highest.

Overall, doravirine has not shown major safety concerns in adults, but more information is needed to understand its effects during pregnancy. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Doravirine is unique because it offers a new option for treating HIV in pregnant individuals. Unlike other treatments that primarily focus on established antiretroviral combinations, doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with a novel structure. Researchers are excited about doravirine because it has shown promise in maintaining viral suppression with a favorable safety profile, which is particularly important during pregnancy. Additionally, its once-daily oral administration makes it a convenient choice, potentially improving adherence to treatment.

What evidence suggests that doravirine might be an effective treatment for HIV in pregnancy?

Research has shown that doravirine effectively controls HIV by maintaining low virus levels in the body, even in individuals with high viral loads. However, insufficient information exists about doravirine's effects during pregnancy, prompting this trial. The trial will specifically assess the safety and effectiveness of doravirine for pregnant women living with HIV. Additionally, researchers are tracking pregnancy outcomes for those taking doravirine, demonstrating a commitment to understanding its impact during pregnancy. ^{1 3 4 5 6}

Who Is on the Research Team?

Angela Kashuba, PharmD

Principal Investigator

UNC Chapel Hill

Are You a Good Fit for This Trial?

This trial is for HIV-positive pregnant women over 18, with stable health and on consistent antiretroviral therapy. They must have low viral loads and normal liver function. Women with severe kidney or liver issues, multiple pregnancies, certain other illnesses, or taking drugs that affect the body's drug processing are excluded.

Inclusion Criteria

I agree not to change my current HIV medication during the study.

Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial

I am a pregnant woman over 18 with HIV.

Exclusion Criteria

I have an active hepatitis C infection confirmed by tests.

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

I have severe kidney or liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of doravirine during each sampling visit in the 2nd and 3rd trimesters, and post-partum

Up to 10 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Doravirine

Trial Overview

The study tests how pregnancy affects the levels of Doravirine (an HIV medication) in the body to determine proper dosing. Participants will take a single dose at different stages of pregnancy and post-delivery while continuing their regular HIV treatments.

How Is the Trial Designed?

Group I: Doravirine Experimental Treatment 1 Intervention

100mg doravirine given by mouth once at each sampling visit.

Doravirine is already approved in United States, European Union for the following indications:

Approved in United States as Pifeltro for:

• HIV-1 infection

Approved in United States as Delstrigo for:

• HIV-1 infection

Approved in European Union as Delstrigo for:

• HIV-1 infection

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Doravirine is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI) for treating HIV-1 infection, available as both a single-agent tablet and a fixed-dose combination with other antiretroviral drugs.

It is specifically indicated for adults with no prior antiretroviral treatment and has received positive regulatory opinions in the USA and EU, highlighting its safety and efficacy for treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine: First Global Approval. Deeks, ED.[2021]

Doravirine, an HIV-1 NNRTI, is capable of crossing the placenta and accumulating in fetal tissue, with a fetal-to-maternal concentration ratio of 16%, indicating potential exposure to the fetus.

While doravirine may help reduce the risk of vertical HIV transmission, its accumulation in the placenta raises concerns about possible fetal toxicities, highlighting the need for further safety and efficacy studies in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placental transfer of doravirine, a recent HIV-1 NNRTI in the ex vivo human cotyledon perfusion model. Lê, MP., Pencolé, L., Peytavin, G., et al.[2021]

In a study of 62 people living with HIV who switched to a single-tablet regimen containing doravirine, lamivudine, and tenofovir, 93.5% maintained viral suppression after 12 months, demonstrating the regimen's efficacy.

The treatment led to significant reductions in triglycerides and total cholesterol levels, indicating improved lipid profiles, while maintaining good tolerability with only minor weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine/lamivudine/tenofovir disoproxil fumarate in virologically suppressed people living with HIV: A real-life experience. Calza, L., Colangeli, V., Pensalfine, G., et al.[2023]

Doravirine shows promise as a treatment option for multidrug-resistant HIV-1, with 23% of cases demonstrating full susceptibility, compared to only 18% for etravirine and 5% for rilpivirine, based on a study of 22 participants with a long history of HIV treatment.

The study found that higher numbers of NNRTI mutations in the virus correlated with increased resistance to doravirine, but doravirine's effectiveness can still be predicted accurately using the Stanford HIVdb algorithm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Residual phenotypic susceptibility to doravirine in multidrug-resistant HIV-1 from subjects enrolled in the PRESTIGIO Registry. Saladini, F., Giammarino, F., Maggiolo, F., et al.[2023]

Doravirine exposure in pregnant women is predicted to be significantly lower (by 55%) compared to nonpregnant women, which may lead to reduced effectiveness in treating HIV during pregnancy.

The study indicates that while doravirine crosses the placenta extensively, the predicted fetal exposure raises concerns about safety, emphasizing the need for monitoring and further clinical data on fetal effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of Maternal and Fetal Doravirine Exposure by Integrating Physiologically Based Pharmacokinetic Modeling and Human Placenta Perfusion Experiments. Bukkems, VE., van Hove, H., Roelofsen, D., et al.[2022]

In a Phase IIb trial involving 342 participants, doravirine 100 mg showed similar effectiveness to efavirenz 600 mg in reducing HIV-1 RNA levels, with 72.9% of doravirine recipients achieving viral suppression compared to 73.1% for efavirenz.

Doravirine was associated with significantly fewer central nervous system adverse events (26.9%) compared to efavirenz (47.2%), indicating a better safety profile for doravirine in this regard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial. Gatell, JM., Morales-Ramirez, JO., Hagins, DP., et al.[2020]

Citations

1.

clinicalinfo.hiv.gov

clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/perinatal-hiv/safety-toxicity-arv-agents-nnrtis-doravirine-pifeltro-perinatal.pdf

Perinatal Guidelines - Doravirine (Pifeltro, DOR)

Pharmacokinetic (PK) data are insufficient to make dosing recommendations for doravirine (DOR) during pregnancy.

2.

merck.com

merck.com/news/merck-to-present-new-data-from-hiv-treatment-and-prevention-pipeline-at-european-aids-conference-2025/

Merck to Present New Data from HIV Treatment and ...

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11095844/

Antiretroviral Therapy in Pregnancy: A 2023 Review of the ...

Data now supports the use of dolutegravir at all stages of pregnancy with no significant increase in neural tube defects.

4.

merckconnect.com

merckconnect.com/doravirine/pifeltro-clinical-efficacy/

Clinical Efficacy Data for PIFELTRO® (doravirine) Tablets

20% of patients at baseline had HIV-1 RNA >100,000 copies/mL. PIFELTRO showed consistent virologic suppression regardless of baseline viral load. View DRIVE- ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01632345

A Dose-Ranging Study to Compare Doravirine (MK-1439) ...

The hypothesis tested in this study is that doravirine (MK-1439) at the final dose selected is superior to efavirenz, each given in combination with ...

6.

clinicalinfo.hiv-stage.od.nih.gov

clinicalinfo.hiv-stage.od.nih.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-nnrtis-doravirine-pifeltro?view=full

Appendix B: Doravirine (Pifeltro) - Safety and Toxicity in Pregnancy

Clinical data are insufficient to characterize the risk for congenital anomalies associated with in utero exposure to DOR. No reproductive toxicity or ...