Evaluating the Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants

• Register: ClinicalTrials.gov
• Last refreshed on: 24 January 2022
• Main ID: NCT03048422
• Date of registration: 07/02/2017
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Evaluating the Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants VESTED
• Scientific title: Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants
• Date of first enrolment: January 19, 2018
• Target sample size: 643
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03048422
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Botswana, Brazil, Haiti, India, Malawi, South Africa, Tanzania, Thailand, Uganda, United States, Zimbabwe

Contacts

• Name: Lameck Chinula, MBBS, MMED, FCOG
• Affiliation: Kamuzu Central Hospital in Lilongwe, Malawi

• Name: Shahin Lockman, MD, MSc
• Affiliation: Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- Mother is able to provide written informed consent for her and her infant's
participation in this study

- Mother has confirmed HIV-1 infection based on documented testing of two samples
collected at different time points:

- Sample #1 may be tested using any of the following:

- Two rapid antibody tests from different manufacturers or based on different
principles and epitopes

- One enzyme immunoassay (EIA) OR Western blot OR immunofluorescence assay OR
chemiluminescence assay

- One HIV DNA polymerase chain reaction (PCR)

- One quantitative HIV RNA PCR (above the limit of detection of the assay)

- One qualitative HIV RNA PCR

- One total HIV nucleic acid test

- Sample #2 may be tested using any of the following:

- One rapid antibody test. If this option is used in combination with two rapid
tests for Sample #1, at least one of the three rapid tests must be FDA-approved
and the third rapid test must be from a third manufacturer or based on a third
principle or epitope.

- One EIA OR Western blot OR immunofluorescence assay OR chemiluminescence assay

- One HIV DNA PCR

- One quantitative HIV RNA PCR (above the limit of detection of the assay)

- One qualitative HIV RNA PCR

- One total HIV nucleic acid test.

- See the protocol for more information on this inclusion criterion.

- At screening, mother is ART-naive, defined as having not received prior antiretroviral
therapy other than ARVs received during prior pregnancies or prior periods of
breastfeeding (i.e., receipt of any single, dual, or triple ARV regimen during prior
time-limited periods of pregnancy and breastfeeding is permitted). Receipt of up to 14
days of ARVs during the current pregnancy is permitted prior to study entry so that
initiation of ARVs during the current pregnancy is not delayed during the study
screening period. Note: Non-study ART may be initiated in the current pregnancy prior
to initiation of the study screening process. For eligible participants, enrollment
must occur within 14 days of non-study ART initiation. Note: Receipt of ARVs during a
prior pregnancy or prior period of breastfeeding must have concluded at least six
months prior to study entry. Receipt of TDF or FTC/TDF for pre-exposure prophylaxis at
any time in the past is not exclusionary (even if received within six months prior to
study entry).

- At screening, mother has the following laboratory test results (based on testing of
samples collected within 14 days prior to study entry):

- Grade 1 or lower (less than 2.5 times upper limit of normal [ULN]) alanine
aminotransferase (ALT) and aspartate aminotransferase (AST)

- Grade 2 or lower (less than or equal to 1.8 times ULN) creatinine

- Grade 2 or lower (greater than or equal to 60 mL/min) estimated creatinine
clearance (CrCl; Cockcroft-Gault formula). See the protocol for guidance on
severity grading. Laboratory tests may be repeated during the study screening
period, with the latest result used for eligibility determination.

- At screening and at study entry, no evidence of multiple gestation or fetal anomalies,
as assessed by best available method

- At study entry, gestational age of 14-28 weeks, defined as greater than 13 weeks plus
six days and less than 28 completed weeks gestation, estimated by best available
method. Note: For this inclusion criterion and the previous inclusion criterion, fetal
ultrasound is preferred but not required for purposes of eligibility determination. If
ultrasound cannot be performed during the study screening period prior to study entry,
it must be performed within 14 days after study entry. As further explained in the
protocol, enrolled participants will not be withdrawn from the study based on
ultrasound findings obtained after study entry.

- At study entry, mother expects to remain in the geographic area of the study site
during pregnancy and for 50 weeks postpartum [Eligibility criteria added per Letter of
Amendment 1 to V2; July 2018]:

- At study entry, mother reports that she does not wish to become pregnant again for at
least 50 weeks after her current pregnancy and that she is willing to use effective
contraception during this period. Effective contraception may include surgical
sterilization (i.e., hysterectomy, bilateral oophorectomy, tubal ligation, or
salpingectomy) or any of the following methods:

- Contraceptive intrauterine device (IUD) or intrauterine system (IUS)

- Subdermal contraceptive implant

- Progestogen injections

- Progestogen only oral contraceptive pills

- Combined estrogen and progestogen oral contraceptive pills

- Percutaneous contraceptive patches

- Contraceptive vaginal rings

- Note: IUDs, IUSs, implants, and injections are strongly recommended due to their
lower failure rates with typical use. Male or female condom use is recommended
with all contraceptive methods for dual protection against pregnancy and to avoid
transmission of HIV and other sexually transmitted infections.

Exclusion Criteria:

- Mother is currently incarcerated or involuntarily confined in a medical facility

- Mother is currently receiving:

- A psychoactive medication for treatment of a psychiatric illness

- Treatment for active tuberculosis

- Treatment for active hepatitis C infection

- Mother is expected to require treatment with interferon and/or ribavirin for hepatitis
C infection during the study follow-up period

- Mother has a history of any of the following, as determined by the site investigator
or designee based on maternal report and available medical records:

- Hypersensitivity or clinically significant adverse reaction to any of the ARVs
included in the three study drug regimens (ever)

- Antiretroviral drug resistance mutations that would impact selection of ART
regimen (ever)

- Clinically significant heart disease and/or known prolonged corrected QT (QTc)
interval (ever)

- Suicidal ideation or attempt (ever)

- HIV-2 infection (ever)

- Zika virus infection, diagnosed or suspected, during the current pregnancy

- R


Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Efavirenz/emtricitabine/tenofovir disoproxil fumarate

Drug: Dolutegravir

Drug: Emtricitabine/tenofovir alafenamide

Drug: Emtricitabine/tenofovir disoproxil fumarate

Primary Outcome(s)

Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery [Time Frame: Delivery]

Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event [Time Frame: From randomization up to 74 weeks]

Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event [Time Frame: From birth through Week 50 postpartum]

Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome [Time Frame: Delivery]

Secondary Outcome(s)

Cumulative Probability of Infant HIV-infection [Time Frame: Birth through 50 weeks after birth]

Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event [Time Frame: Birth through Week 50 postpartum]

Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm [Time Frame: Delivery]

Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event [Time Frame: From randomization up to 74 weeks]

Percentage of Mother-Infant Pairs With Preterm Deliveries [Time Frame: Delivery]

Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum [Time Frame: 50 weeks postpartum]

Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory [Time Frame: Delivery]

Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome [Time Frame: Delivery]

Change in Maternal Weight Antepartum [Time Frame: Baseline through before delivery (up to one day prior)]

Cumulative Probability of Infant Deaths [Time Frame: Birth through 50 weeks after birth]

Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery [Time Frame: Randomization to delivery]

Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome [Time Frame: Birth through 50 weeks postpartum]

Percentage of Infants Born Small for Gestational Age [Time Frame: Birth]

Maternal Change in Creatinine Clearance [Time Frame: Baseline to 50 weeks postpartum]

Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure [Time Frame: From 24 weeks after randomization through Week 50 postpartum]

Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm [Time Frame: 50 weeks postpartum]

Infant Creatinine Clearance [Time Frame: Delivery and 26 weeks postpartum]

Percentage of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis [Time Frame: From birth through 50 weeks postpartum]

Change in Maternal Weight Overall [Time Frame: Baseline to 50 weeks postpartum]

Change in Maternal Weight Postpartum [Time Frame: Delivery to 50 weeks postpartum]

Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly [Time Frame: Delivery through 50 weeks postpartum]

Secondary ID(s)

30129

IMPAACT 2010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/11/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03048422