HIV InfectionsPhase 3VESTEDNCT03048422
Evaluating the Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants
A Phase 3 study testing Dolutegravir, Emtricitabine/tenofovir alafenamide and Emtricitabine/tenofovir disoproxil fumarate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in 9 countries.
Trial summary
The purpose of this study was to compare the virologic efficacy and safety of three antiretroviral (ARV) regimens, dolutegravir plus emtricitabine/tenofovir alafenamide, dolutegravir plus emtricitabine/tenofovir disoproxil fumarate, and efavirenz/emtricitabine/tenofovir disoproxil fumarate in pregnant women living… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV Infections
- What is being tested?
- Dolutegravir, Emtricitabine/tenofovir alafenamide and Emtricitabine/tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 643 participants
- Where
- 21 sitesin 9 countries
- Study dates
- 19 Jan 2018to 3 Oct 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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
- Receipt of any antiretroviral medication within six months prior to study entry, with two exceptions: receipt of any duration of TDF or FTC/TDF for pre-exposure prophylaxis or receipt of up to 14 days of ARVs during the current pregnancy
- Receipt of any prohibited medication within 14 days prior to study entry (see the protocol for more information)
- Clinically significant acute illness requiring systemic treatment and/or hospitalization (i.e., major medical condition that is likely to lead to hospitalization and/or to an adverse pregnancy outcome) within 14 days prior to study entry
- Unstable liver disease (defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) within 14 days prior to study entry
- Note: Testing to rule out HIV-2 infection is not required.
- Mother or fetus has any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Trial locations and contacts
21 sites in 9 countries.
21 sites in 9 countries
Brazil4 sites
SOM Federal University Minas Gerais Brazil NICHD CRS
Belo Horizonte, Minas Gerais, 30.130-100
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
Rio de Janeiro, 21941-612
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, 26030
South Africa4 sites
Umlazi CRS
Durban, KwaZulu-Natal, 4001
Soweto IMPAACT CRS
Johannesburg, Gauteng, 1862
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, 2001
Famcru Crs
Tygerberg, Western Cape, 7505
Thailand3 sites
Siriraj Hospital ,Mahidol University NICHD CRS
Bangkok, Bangkoknoi, 10700
Chiangrai Prachanukroh Hospital NICHD CRS
Chiang Mai, 50100
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
Zimbabwe3 sites
Seke North CRS
Chitungwiza
St Mary's CRS
Chitungwiza
Harare Family Care CRS
Harare
United States2 sites
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, 32209
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, 33136
Botswana2 sites
Gaborone CRS
Gaborone, South-East District
Molepolole CRS
Gaborone
India1 site
Byramjee Jeejeebhoy Medical College (BJMC) CRS
Pune, Maharashtra, 411001
About this study
Official 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
The purpose of this study was to compare the virologic efficacy and safety of three antiretroviral (ARV) regimens, dolutegravir plus emtricitabine/tenofovir alafenamide, dolutegravir plus emtricitabine/tenofovir disoproxil fumarate, and efavirenz/emtricitabine/tenofovir disoproxil fumarate in pregnant women living with HIV-1 and to compare the safety of these regimens for their infants.
Read the detailed description
This study compared the virologic efficacy and safety of three ARV regimens in pregnant women living with HIV: dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF), DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). The study also compared the safety of these regimens for their infants.
At study entry, mothers were randomly assigned to either receive DTG plus FTC/TAF (Arm 1), DTG plus FTC/TDF (Arm 2), or EFV/FTC/TDF (Arm 3) during pregnancy, through delivery, and for 50 weeks postpartum.
Mothers completed study visits at study entry and every four weeks during pregnancy. Study visits for mothers and their infants occurred at delivery and at 6, 14, 26, 38, and 50 weeks postpartum. Visits for mothers and infants included physical examinations and blood collection. Select study visits also included breast milk collection from mothers who breastfed, hair and urine collection, ultrasound scans, pregnancy testing, contraception counseling, and, for a subset of participants, dual energy x-ray absorptiometry (DXA) scans for mothers and their infants.
For pregnancy outcome measures, mothers and infants were evaluated together as mother-infant pairs, with any outcome between the two counting as an event (for example, if an infant was born small for gestational age, this would be a pregnancy outcome event for the mother-infant pair). For all other outcome measures, women and infants were evaluated separately.
- Conditions
- HIV Infections
- Being tested
- Dolutegravir, Emtricitabine/tenofovir alafenamide, Emtricitabine/tenofovir disoproxil fumarate, Efavirenz/emtricitabine/tenofovir disoproxil fumarate
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DolutegravirDrug
Also called DTG
One 50 mg DTG tablet was administered orally once daily
Emtricitabine/tenofovir alafenamideDrug
Also called FTC/TAF
One fixed-dose combination tablet (FTC 200 mg/TAF 25 mg) was administered orally once daily
Emtricitabine/tenofovir disoproxil fumarateDrug
Also called FTC/TDF
One fixed-dose combination tablet (FTC 200 mg/TDF 300 mg) was administered orally once daily
Efavirenz/emtricitabine/tenofovir disoproxil fumarateDrug
Also called EFV/FTC/TDF
One fixed-dose combination tablet (EFV 600 mg/FTC 200 mg/TDF 300 mg) was administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Maternal DTG+FTC/TAF | Experimental | Mothers randomized to receive dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF) during pregnancy, through delivery, and for 50 weeks postpartum. Receives: Drug: Dolutegravir; Drug: Emtricitabine/tenofovir alafenamide |
| Arm 2: Maternal DTG+FTC/TDF | Experimental | Mothers randomized to receive DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum. Receives: Drug: Dolutegravir; Drug: Emtricitabine/tenofovir disoproxil fumarate |
| Arm 3: Maternal EFV/FTC/TDF | Active comparator | Mothers randomized to receive efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum. Receives: Drug: Efavirenz/emtricitabine/tenofovir disoproxil fumarate |
| Arm 1 Infants | No intervention | Infants born to women in Arm 1. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
| Arm 2 Infants | No intervention | Infants born to women in Arm 2. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
| Arm 3 Infants | No intervention | Infants born to women in Arm 3. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery
Percentage of mothers with plasma HIV-1 RNA viral load less than 200 copies/mL at delivery determined using real-time test results obtained at site laboratories. This outcome was evaluated in the non-inferiority (primary outcome) and superiority (secondary outcome) analyses. The intention-to-treat analysis included all randomized women who had viral load data available. The per-protocol analysis excluded women who modified randomized treatment (stopped, paused, switched, added any treatment) before viral load evaluation at delivery, with the exception of women who modified randomized treatment for use of a concomitant medication.
Measured: Delivery
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome
Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (<37 completed weeks), or small for gestational age (<10th percentile by INTERGROWTH 21st Standards)
Measured: Delivery
Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks.
Measured: From randomization up to 74 weeks
Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Measured: From birth through Week 50 postpartum
Secondary outcomes (21)
Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory
Percentage of mothers with HIV-1 RNA less than 50 copies/mL at delivery using batched test results obtained from central laboratory
Measured: Delivery
Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum
Percentage of mothers with HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum using real-time test results obtained from site laboratories
Measured: 50 weeks postpartum
Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery
Time to first viral HIV-1 RNA less than 200 copies/mL through delivery, determined using real-time results obtained from site laboratories
Measured: Randomization to delivery
Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm
Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at delivery based on FDA snapshot algorithm using real-time test results obtained from site laboratories
Measured: Delivery
Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm
Percentage of mothers with virologic success of HIV-1 RNA less than 200 copies/mL at 50 weeks postpartum based on FDA snapshot algorithm using real-time test results obtained from site laboratories
Measured: 50 weeks postpartum
Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome
Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (<37 completed weeks), or small for gestational age (<10th percentile per INTERGROWTH 21st Standards)
Measured: Delivery
Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks.
Measured: From randomization up to 74 weeks
Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event
The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
Measured: Birth through Week 50 postpartum
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly
Percentage of mother-infant pairs with an adverse pregnancy outcome or major congenital anomaly. Adverse pregnancy outcomes include spontaneous abortions (<20 weeks gestation), stillbirths (≥20 weeks gestation), preterm deliveries (<37 weeks gestation), and infants small for gestational age (<10th percentile per INTERGROWTH 21st Standards). Major congenital anomaly was defined consistent with the definition of malformation provided by Holmes and Westgate (i.e., a structural abnormality with surgical, medical, or cosmetic importance) and evaluated by an internal study team blinded to treatment arm.
Measured: Delivery through 50 weeks postpartum
Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome
Infant and pregnancy outcomes were classified on a scale of 1 to 10, with mother-infant pairs categorized by the worst outcome they experienced (worst category being 1 and best being 10): 1) Infant death; 2) Spontaneous abortion (<20 weeks gestation) or stillbirth (≥20 weeks gestation); 3) Infant HIV infection; 4) Extremely and very early preterm (<32 completed weeks); 5) Major congenital anomaly; 6) Preterm delivery (<37 completed weeks); 7) Small for gestational age (<10th percentile); 8) Infant hospitalization; 9) Infant grade 3 or 4 adverse event; 10) None of the above. If a mother-infant pair experienced more than one safety outcome, only the worst was reported.
Measured: Birth through 50 weeks postpartum
Cumulative Probability of Infant HIV-infection
The Kaplan-Meier estimate of the cumulative probability of infants acquiring HIV-1 infection from birth through 50 weeks after birth based on nucleic acid test results.
Measured: Birth through 50 weeks after birth
Cumulative Probability of Infant Deaths
The Kaplan-Meier estimate of the cumulative probability of infant deaths from birth through 50 weeks after birth.
Measured: Birth through 50 weeks after birth
Maternal Change in Creatinine Clearance
Maternal change in creatinine clearance per week based on generalized estimating equations
Measured: Baseline to 50 weeks postpartum
Infant Creatinine Clearance
Infant creatinine clearance based on Schwartz formula
Measured: Delivery and 26 weeks postpartum
Percentage of Mothers With HIV-1 ARV Drug Resistance Mutations at the Time of Maternal Virologic Failure
Percentage of mothers with HIV-1 antiretroviral (ARV) drug resistance mutations at the time of maternal virologic failure. Virologic failure was defined as two consecutive plasma HIV-1 RNA viral loads <200 copies/mL on or after 24 weeks on study. Drug resistance mutations were assessed using the Stanford algorithm, and all ARV regimens were assessed for mutations.
Measured: From 24 weeks after randomization through Week 50 postpartum
Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis
Count of infants with HIV-1 antiretroviral drug resistance mutations (to any antiretroviral drug) at the time of infant HIV diagnosis, based on laboratory blood test results.
Measured: From birth through 50 weeks postpartum
Percentage of Mother-Infant Pairs With Preterm Deliveries
Percentage of mother-infant pairs with preterm deliveries (<37 weeks gestation) resulting in live born infant
Measured: Delivery
Percentage of Infants Born Small for Gestational Age
Percentage of infants born small for gestational age (<10th percentile adjusted for sex assigned at birth) based on Intergrowth 21st Standards
Measured: Birth
Change in Maternal Weight Antepartum
Change in maternal antepartum weight per week based on generalized estimating equations
Measured: Baseline through before delivery (up to one day prior)
Change in Maternal Weight Postpartum
Change in maternal postpartum weight per week based on generalized estimating equations
Measured: Delivery to 50 weeks postpartum
Change in Maternal Weight Overall
Change in maternal weight per week based on generalized estimating equations
Measured: Baseline to 50 weeks postpartum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study start19 Jan 2018
- Primary completion3 Oct 2020
- Study completion3 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 643 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Shahin Lockman, MD, MSc, Study chair, Harvard T.H. Chan School of Public Health and Brigham and Women's HospitalLameck Chinula, MBBS, MMED, FCOG, Study chair, Kamuzu Central Hospital in Lilongwe, Malawi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03048422
- Sponsor's protocol ID
- IMPAACT 2010
- Other IDs
- 30129
- Acronym
- VESTED
- Status last verified
- Jul 2026
- First submitted
- 7 Feb 2017
- Last updated
- 31 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification
Publications
Lockman S, Brummel SS, Ziemba L, Stranix-Chibanda L, McCarthy K, Coletti A, Jean-Philippe P, Johnston B, Krotje C, Fairlie L, Hoffman RM, Sax PE, Moyo S, Chakhtoura N, Stringer JS, Masheto G, Korutaro V, Cassim H, Mmbaga BT, Joao E, Hanley S, Purdue L, Holmes LB, Momper JD, Shapiro RL, Thoofer NK, Rooney JF, Frenkel LM, Amico KR, Chinula L, Currier J; IMPAACT 2010/VESTED Study Team and Investigators. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2021 Apr 3;397(10281):1276-1292. doi: 10.1016/S0140-6736(21)00314-7.
PubMed 33812487Masheto G, Brummel SS, Ziemba L, Shepherd J, Mbengeranwa T, Igawa L, Coletti A, Mukura D, Rossouw L, Theron G, Krotje C, Jean-Philippe P, Chakhtoura N, Cassim H, Mathiba SR, Maena J, Murtaugh W, Fairlie L, Currier J, Hoffman R, Chinula L, Sax PE, Stranix-Chibanda L, Lockman S; IMPAACT 2010/VESTED Study Team and Investigators. Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial. J Acquir Immune Defic Syndr. 2024 Oct 1;97(2):172-179. doi: 10.1097/QAI.0000000000003478.
PubMed 39250651Eke AC, Brummel SS, Aliyu MH, Stranix-Chibanda L, Eleje GU, Ezebialu IU, Korutaro V, Wabwire D, Matubu A, Mbengeranwa T, Chakhtoura N, Chinula L, McCarthy K, Knowles K, Krotje C, Linton MF, Dooley KE, Sax PE, Brown T, Lockman S; IMPAACT 2010/VESTED Study Team. Lipid and Glucose Profiles in Pregnant Women With HIV on Tenofovir-based Antiretroviral Therapy. Clin Infect Dis. 2025 Mar 17;80(3):594-601. doi: 10.1093/cid/ciae441.
PubMed 39219495Jacobson DL, Crider KS, DeMarrais P, Brummel S, Zhang M, Pfeiffer CM, Moore CA, McCarthy K, Johnston B, Mohammed T, Vhembo T, Kabugho E, Muzorah GA, Cassim H, Fairlie L, Machado ES, Ngocho JS, Shapiro RL, Serghides L, Chakhtoura N, Chinula L, Lockman S. Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants. J Infect Dis. 2024 Nov 15;230(5):1224-1234. doi: 10.1093/infdis/jiae308.
PubMed 38877762Chinula L, Ziemba L, Brummel S, McCarthy K, Coletti A, Krotje C, Johnston B, Knowles K, Moyo S, Stranix-Chibanda L, Hoffman R, Sax PE, Stringer J, Chakhtoura N, Jean-Philippe P, Korutaro V, Cassim H, Fairlie L, Masheto G, Boyce C, Frenkel LM, Amico KR, Purdue L, Shapiro R, Mmbaga BT, Patel F, van Wyk J, Rooney JF, Currier JS, Lockman S; IMPAACT 2010/VESTED Study Team and Investigators. Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet HIV. 2023 Jun;10(6):e363-e374. doi: 10.1016/S2352-3018(23)00061-9. Epub 2023 May 8.
PubMed 37167996
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03048422
- Acronym / sponsor ID
- VESTED / IMPAACT 2010
- Conditions
- HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 643 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 19 Jan 2018 (actual)
- Primary completion
- 3 Oct 2020 (actual)
- Study completion
- 3 Oct 2020 (actual)
- First posted
- 9 Feb 2017 (estimated)
- Results
- Posted 10 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to compare the virologic efficacy and safety of three antiretroviral (ARV) regimens, dolutegravir plus emtricitabine/tenofovir alafenamide, dolutegravir plus emtricitabine/tenofovir disoproxil fumarate, and efavirenz/emtricitabine/tenofovir disoproxil fumarate in pregnant women living with HIV-1 and to compare the safety of these regimens for their infants.
Detailed description
This study compared the virologic efficacy and safety of three ARV regimens in pregnant women living with HIV: dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF), DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). The study also compared the safety of these regimens for their infants.
At study entry, mothers were randomly assigned to either receive DTG plus FTC/TAF (Arm 1), DTG plus FTC/TDF (Arm 2), or EFV/FTC/TDF (Arm 3) during pregnancy, through delivery, and for 50 weeks postpartum.
Mothers completed study visits at study entry and every four weeks during pregnancy. Study visits for mothers and their infants occurred at delivery and at 6, 14, 26, 38, and 50 weeks postpartum. Visits for mothers and infants included physical examinations and blood collection. Select study visits also included breast milk collection from mothers who breastfed, hair and urine collection, ultrasound scans, pregnancy testing, contraception counseling, and, for a subset of participants, dual energy x-ray absorptiometry (DXA) scans for mothers and their infants.
For pregnancy outcome measures, mothers and infants were evaluated together as mother-infant pairs, with any outcome between the two counting as an event (for example, if an infant was born small for gestational age, this would be a pregnancy outcome event for the mother-infant pair). For all other outcome measures, women and infants were evaluated separately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Maternal DTG+FTC/TAF | Experimental | Drug: Dolutegravir, Drug: Emtricitabine/tenofovir alafenamideMothers randomized to receive dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF) during pregnancy, through delivery, and for 50 weeks postpartum. |
| Arm 2: Maternal DTG+FTC/TDF | Experimental | Drug: Dolutegravir, Drug: Emtricitabine/tenofovir disoproxil fumarateMothers randomized to receive DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum. |
| Arm 3: Maternal EFV/FTC/TDF | Active comparator | Drug: Efavirenz/emtricitabine/tenofovir disoproxil fumarateMothers randomized to receive efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum. |
| Arm 1 Infants | No intervention | –Infants born to women in Arm 1. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
| Arm 2 Infants | No intervention | –Infants born to women in Arm 2. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
| Arm 3 Infants | No intervention | –Infants born to women in Arm 3. Infants did not directly receive study intervention, but may have been exposed to the randomized treatment through placental or breastmilk transfer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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:
- 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):
- At screening and at study entry, no evidence of multiple gestation or fetal anomalies, as assessed by best available method
Key exclusion criteria (19 listed)
- Mother is currently incarcerated or involuntarily confined in a medical facility
- Mother is currently receiving:
- 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:
- Mother or fetus has any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DolutegravirAlso: DTGOne 50 mg DTG tablet was administered orally once daily | Drug | Arm 1: Maternal DTG+FTC/TAF, Arm 2: Maternal DTG+FTC/TDF |
| Emtricitabine/tenofovir alafenamideAlso: FTC/TAFOne fixed-dose combination tablet (FTC 200 mg/TAF 25 mg) was administered orally once daily | Drug | Arm 1: Maternal DTG+FTC/TAF |
| Emtricitabine/tenofovir disoproxil fumarateAlso: FTC/TDFOne fixed-dose combination tablet (FTC 200 mg/TDF 300 mg) was administered orally once daily | Drug | Arm 2: Maternal DTG+FTC/TDF |
| Efavirenz/emtricitabine/tenofovir disoproxil fumarateAlso: EFV/FTC/TDFOne fixed-dose combination tablet (EFV 600 mg/FTC 200 mg/TDF 300 mg) was administered orally once daily | Drug | Arm 3: Maternal EFV/FTC/TDF |
Primary outcome
Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery
Time frame: Delivery
Percentage of mothers with plasma HIV-1 RNA viral load less than 200 copies/mL at delivery determined using real-time test results obtained at site laboratories. This outcome was evaluated in the non-inferiority (primary outcome) and superiority (secondary outcome) analyses. The intention-to-treat analysis included all randomized women who had viral load data available. The per-protocol analysis excluded women who modified randomized treatment (stopped, paused, switched, added any treatment) before viral load evaluation at delivery, with the exception of women who modified randomized treatment for use of a concomitant medication.
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome
Time frame: Delivery
Percentage of mother-infant pairs with an adverse pregnancy outcome. Adverse pregnancy outcome includes spontaneous abortion (<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (<37 completed weeks), or small for gestational age (<10th percentile by INTERGROWTH 21st Standards)
Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event
Time frame: From randomization up to 74 weeks
The Kaplan-Meier estimate of the cumulative probability of women experiencing grade 3 or higher adverse events, including events resulting in death due to any cause. Time to first maternal grade 3 or higher adverse event was defined as the first grade 3 or higher adverse event that occurred after randomization and before 74 weeks of follow-up. The timeframe of 74 weeks was determined by adding up 56 weeks of postpartum follow-up to the mean duration of antepartum follow-up, which was 18 weeks.
Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event
Time frame: From birth through Week 50 postpartum
The Kaplan-Meier estimate of the cumulative probability of infants experiencing grade 3 or higher adverse events, including events resulting in death due to any cause.
21 secondary outcomes
Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory
Time frame: Delivery
Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum
Time frame: 50 weeks postpartum
Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery
Time frame: Randomization to delivery
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
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
Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome
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: Birth through Week 50 postpartum
Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome or Major Congenital Anomaly
Time frame: Delivery through 50 weeks postpartum
Count of Mother-infant Pairs in the Classified Ranked Composite Safety Outcome
Time frame: Birth through 50 weeks postpartum
Cumulative Probability of Infant HIV-infection
Time frame: Birth through 50 weeks after birth
Cumulative Probability of Infant Deaths
Time frame: Birth through 50 weeks after birth
Maternal Change in Creatinine Clearance
Time frame: Baseline to 50 weeks postpartum
Infant Creatinine Clearance
Time frame: Delivery and 26 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
Count of Infants With HIV-1 Antiretroviral Drug Resistance Mutations at the Time of Infant HIV Diagnosis
Time frame: From birth through 50 weeks postpartum
Percentage of Mother-Infant Pairs With Preterm Deliveries
Time frame: Delivery
Percentage of Infants Born Small for Gestational Age
Time frame: Birth
Change in Maternal Weight Antepartum
Time frame: Baseline through before delivery (up to one day prior)
Change in Maternal Weight Postpartum
Time frame: Delivery to 50 weeks postpartum
Change in Maternal Weight Overall
Time frame: Baseline to 50 weeks postpartum
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33812487Lockman S, Brummel SS, Ziemba L, Stranix-Chibanda L, McCarthy K, Coletti A, Jean-Philippe P, Johnston B, Krotje C, Fairlie L, Hoffman RM, Sax PE, Moyo S, Chakhtoura N, Stringer JS, Masheto G, Korutaro V, Cassim H, Mmbaga BT, Joao E, Hanley S, Purdue L, Holmes LB, Momper JD, Shapiro RL, Thoofer NK, Rooney JF, Frenkel LM, Amico KR, Chinula L, Currier J; IMPAACT 2010/VESTED Study Team and Investigators. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2021 Apr 3;397(10281):1276-1292. doi: 10.1016/S0140-6736(21)00314-7.
- Derived from this study: PubMed 39250651Masheto G, Brummel SS, Ziemba L, Shepherd J, Mbengeranwa T, Igawa L, Coletti A, Mukura D, Rossouw L, Theron G, Krotje C, Jean-Philippe P, Chakhtoura N, Cassim H, Mathiba SR, Maena J, Murtaugh W, Fairlie L, Currier J, Hoffman R, Chinula L, Sax PE, Stranix-Chibanda L, Lockman S; IMPAACT 2010/VESTED Study Team and Investigators. Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial. J Acquir Immune Defic Syndr. 2024 Oct 1;97(2):172-179. doi: 10.1097/QAI.0000000000003478.
- Derived from this study: PubMed 39219495Eke AC, Brummel SS, Aliyu MH, Stranix-Chibanda L, Eleje GU, Ezebialu IU, Korutaro V, Wabwire D, Matubu A, Mbengeranwa T, Chakhtoura N, Chinula L, McCarthy K, Knowles K, Krotje C, Linton MF, Dooley KE, Sax PE, Brown T, Lockman S; IMPAACT 2010/VESTED Study Team. Lipid and Glucose Profiles in Pregnant Women With HIV on Tenofovir-based Antiretroviral Therapy. Clin Infect Dis. 2025 Mar 17;80(3):594-601. doi: 10.1093/cid/ciae441.
- Derived from this study: PubMed 38877762Jacobson DL, Crider KS, DeMarrais P, Brummel S, Zhang M, Pfeiffer CM, Moore CA, McCarthy K, Johnston B, Mohammed T, Vhembo T, Kabugho E, Muzorah GA, Cassim H, Fairlie L, Machado ES, Ngocho JS, Shapiro RL, Serghides L, Chakhtoura N, Chinula L, Lockman S. Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants. J Infect Dis. 2024 Nov 15;230(5):1224-1234. doi: 10.1093/infdis/jiae308.
- Derived from this study: PubMed 37167996Chinula L, Ziemba L, Brummel S, McCarthy K, Coletti A, Krotje C, Johnston B, Knowles K, Moyo S, Stranix-Chibanda L, Hoffman R, Sax PE, Stringer J, Chakhtoura N, Jean-Philippe P, Korutaro V, Cassim H, Fairlie L, Masheto G, Boyce C, Frenkel LM, Amico KR, Purdue L, Shapiro R, Mmbaga BT, Patel F, van Wyk J, Rooney JF, Currier JS, Lockman S; IMPAACT 2010/VESTED Study Team and Investigators. Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet HIV. 2023 Jun;10(6):e363-e374. doi: 10.1016/S2352-3018(23)00061-9. Epub 2023 May 8.
- Study websiteLink provided by the sponsor.
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017, was usedLink provided by the sponsor.
- Intergrowth 21st Standards, including reference for infants small for gestational ageLink provided by the sponsor.
- FDA Snapshot algorithmLink provided by the sponsor.
- Definition for major congenital anomaliesLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shahin Lockman, MD, MSc study chair
Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital
Lameck Chinula, MBBS, MMED, FCOG study chair
Kamuzu Central Hospital in Lilongwe, Malawi
21 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dolutegravir, Emtricitabine/tenofovir alafenamide and Emtricitabine/tenofovir disoproxil fumarate in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Brazil, South Africa, Thailand, Zimbabwe, United States and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery (time frame: Delivery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03048422, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.