NCT03048422: VESTED

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

Completed Phase 3 Results posted Last updated 21 November 2022

What this trial tests

Phase 3 trial testing Dolutegravir in HIV Infections in 643 participants. Completed in 3 October 2020.

Timeline

19 January 2018

Primary endpoint
3 October 2020

3 October 2020

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	643
Start date	19 January 2018
Primary completion	3 October 2020
Estimated completion	3 October 2020
Sites	21 locations across Zimbabwe, South Africa, Tanzania, Uganda, Botswana, Thailand, United States, Brazil

Drugs / interventions tested

• Dolutegravir (DOLUTEGRAVIR) — full drug profile →
• Emtricitabine/tenofovir alafenamide — full drug profile →
• Emtricitabine/tenofovir disoproxil fumarate — full drug profile →
• Efavirenz/emtricitabine/tenofovir disoproxil fumarate — full drug profile →

Conditions studied

• HIV Infections — all drugs for HIV Infections →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

18 and older, female only, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Mothers With HIV-1 RNA Viral Load Less Than 200 Copies/mL at Delivery Primary · 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

Intention-to-Treat Analysis

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	97.5
Arm 3: Maternal EFV/FTC/TDF	91.0

Per-Protocol Analysis

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	97.5
Arm 3: Maternal EFV/FTC/TDF	91.4

Percentage of Mother-infant Pairs With an Adverse Pregnancy Outcome Primary · 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)

Group	Value	95% CI
Arm 1: Maternal DTG+FTC/TAF	24.1
Arm 2: Maternal DTG+FTC/TDF	32.9
Arm 3: Maternal EFV/FTC/TDF	32.7

Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event Primary · 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.

Group	Value	95% CI
Arm 1: Maternal DTG+FTC/TAF	25.1
Arm 2: Maternal DTG+FTC/TDF	30.8
Arm 3: Maternal EFV/FTC/TDF	27.9

Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event Primary · 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.

Group	Value	95% CI
Arm 1 Infants	25.3
Arm 2 Infants	28.6
Arm 3 Infants	30.9

Percentage of Mothers With HIV-1 RNA Less Than 50 Copies/mL at Delivery Measured at Central Laboratory Secondary · Delivery

Percentage of mothers with HIV-1 RNA less than 50 copies/mL at delivery using batched test results obtained from central laboratory

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	94.4
Arm 3: Maternal EFV/FTC/TDF	78.8

Percentage of Mothers With HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Secondary · 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

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	96.3
Arm 3: Maternal EFV/FTC/TDF	96.4

Time to First HIV-1 RNA Less Than 200 Copies/mL Through Delivery Secondary · Randomization to delivery

Time to first viral HIV-1 RNA less than 200 copies/mL through delivery, determined using real-time results obtained from site laboratories

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	4.26	± 0.09
Arm 3: Maternal EFV/FTC/TDF	6.49	± 0.31

Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at Delivery Based on FDA Snapshot Algorithm Secondary · Delivery

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

Group	Value	95% CI
Arm 1: Maternal DTG+FTC/TAF	88.9
Arm 2: Maternal DTG+FTC/TDF	92.6
Arm 3: Maternal EFV/FTC/TDF	81.0

Percentage of Mothers With Virologic Success of HIV-1 RNA Less Than 200 Copies/mL at 50 Weeks Postpartum Based on FDA Snapshot Algorithm Secondary · 50 weeks 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 using real-time test results obtained from site laboratories

Group	Value	95% CI
Arm 1: Maternal DTG+FTC/TAF	75.6
Arm 2: Maternal DTG+FTC/TDF	77.7
Arm 3: Maternal EFV/FTC/TDF	76.3

Percentage of Mother-Infant Pairs With an Adverse Pregnancy Outcome Secondary · 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 per INTERGROWTH 21st Standards)

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	28.4
Arm 3: Maternal EFV/FTC/TDF	32.7

Cumulative Probability of Women Experiencing Grade 3 or Higher Adverse Event Secondary · 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.

Group	Value	95% CI
Arms 1 and 2: Maternal DTG+FTC/TAF and DTG+FTC/TDF	27.9
Arm 3: Maternal EFV/FTC/TDF	27.9

Cumulative Probability of Infants Experiencing Grade 3 or Higher Adverse Event Secondary · 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.

Group	Value	95% CI
Arms 1 and 2 Infants	26.8
Arm 3 Infants	30.9

Adverse events — posted to ClinicalTrials.gov

Time frame: For women, adverse events were reported from randomization through study visit occurring at 50 weeks postpartum. For infants, adverse events were reported from birth through the study visit occurring at 50 weeks post birth.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: Maternal DTG+FTC/TAF

Serious: 39/217 (18%)

Deaths: 1/217

Arm 2: Maternal DTG+FTC/TDF

Serious: 39/215 (18%)

Deaths: 0/215

Arm 3: Maternal EFV/FTC/TDF

Serious: 40/211 (19%)

Deaths: 0/211

Arm 1 Infants

Serious: 35/208 (17%)

Deaths: 2/208

Arm 2 Infants

Serious: 29/202 (14%)

Deaths: 4/202

Arm 3 Infants

Serious: 44/207 (21%)

Deaths: 14/207

Serious adverse events (154 terms)

Reaction	System	Arm 1: Maternal DTG+FTC/TAF	Arm 2: Maternal DTG+FTC/TDF	Arm 3: Maternal EFV/FTC/TDF	Arm 1 Infants	Arm 2 Infants	Arm 3 Infants
Sepsis neonatal	Infections and infestations	—	—	—	—	—	—
Foetal death	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Gestational hypertension	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Hypoxic-ischaemic encephalopathy	Nervous system disorders	—	—	—	—	—	—
Foetal distress syndrome	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Premature baby	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Meconium aspiration syndrome	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Neonatal respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pre-eclampsia	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Premature delivery	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Preterm premature rupture of membranes	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Atrial septal defect	Congenital, familial and genetic disorders	—	—	—	—	—	—
Death neonatal	General disorders	—	—	—	—	—	—
Bronchiolitis	Infections and infestations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Haemoglobin decreased	Investigations	—	—	—	—	—	—
Oligohydramnios	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Postpartum haemorrhage	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Premature rupture of membranes	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Stillbirth	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Neonatal asphyxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Transient tachypnoea of the newborn	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Congenital skin dimples	Congenital, familial and genetic disorders	—	—	—	—	—	—

Other adverse events (124 terms — click to expand)

Reaction	System	Arm 1: Maternal DTG+FTC/TAF	Arm 2: Maternal DTG+FTC/TDF	Arm 3: Maternal EFV/FTC/TDF	Arm 1 Infants	Arm 2 Infants	Arm 3 Infants
Creatinine renal clearance decreased	Investigations	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—
Haemoglobin decreased	Investigations	—	—	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Blood glucose decreased	Investigations	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Anaemia of pregnancy	Blood and lymphatic system disorders	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Gestational hypertension	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Iron deficiency anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Polydactyly	Congenital, familial and genetic disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Blood pressure increased	Investigations	—	—	—	—	—	—
Foetal distress syndrome	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Jaundice neonatal	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Low birth weight baby	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Oligohydramnios	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Pre-eclampsia	Pregnancy, puerperium and perinatal conditions	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—
Anaemia of chronic disease	Blood and lymphatic system disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Congenital joint malformation	Congenital, familial and genetic disorders	—	—	—	—	—	—
Congenital toxoplasmosis	Congenital, familial and genetic disorders	—	—	—	—	—	—
Congenital umbilical hernia	Congenital, familial and genetic disorders	—	—	—	—	—	—
Trisomy 21	Congenital, familial and genetic disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Developmental delay	General disorders	—	—	—	—	—	—
Macrosomia	General disorders	—	—	—	—	—	—
Hypersensitivity	Immune system disorders	—	—	—	—	—	—
Immune reconstitution inflammatory syndrome	Immune system disorders	—	—	—	—	—	—
Acarodermatitis	Infections and infestations	—	—	—	—	—	—
Amniotic cavity infection	Infections and infestations	—	—	—	—	—	—
Bronchiolitis	Infections and infestations	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—
Conjunctivitis	Infections and infestations	—	—	—	—	—	—

Most-reported serious reactions: Sepsis neonatal, Foetal death, Gestational hypertension, Pneumonia, Hypoxic-ischaemic encephalopathy, Foetal distress syndrome, Premature baby, Meconium aspiration syndrome.

Data from ClinicalTrials.gov NCT03048422 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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 multicentr
   Lockman S, Brummel SS, Ziemba L, Stranix-Chibanda L, et al · · 2021 · cited 126× · PMID 33812487 · DOI 10.1016/s0140-6736(21)00314-7
2. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial.
   Kintu K, Malaba TR, Nakibuka J, Papamichael C, et al · · 2020 · cited 97× · PMID 32386721 · DOI 10.1016/s2352-3018(20)30050-3
3. Tenofovir alafenamide use in pregnant and lactating women living with HIV.
   Eke AC, Brooks KM, Gebreyohannes RD, Sheffield JS, et al · · 2020 · cited 26× · PMID 32125906 · DOI 10.1080/17425255.2020.1738384
4. 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.
   Chinula L, Ziemba L, Brummel S, McCarthy K, et al · · 2023 · cited 19× · PMID 37167996 · DOI 10.1016/s2352-3018(23)00061-9
5. Unexpected interactions between dolutegravir and folate: randomized trial evidence from South Africa.
   Chandiwana NC, Chersich M, Venter WDF, Akpomiemie G, et al · · 2021 · cited 13× · PMID 33086234 · DOI 10.1097/qad.0000000000002741
6. Weight Changes and Adverse Pregnancy Outcomes With Dolutegravir- and Tenofovir Alafenamide Fumarate-Containing Antiretroviral Treatment Regimens During Pregnancy and Postpartum.
   Hoffman RM, Brummel S, Ziemba L, Chinula L, et al · · 2024 · cited 7× · PMID 38180851 · DOI 10.1093/cid/ciae001
7. Real-world experience with weight gain among pregnant women living with HIV who are using integrase inhibitors.
   Fuller T, Fragoso da Silveira Gouvêa MI, Benamor Teixeira ML, Ferreira Medeiros A, et al · · 2023 · cited 6× · PMID 36065478 · DOI 10.1111/hiv.13388
8. Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery.
   Lallemant M, Amzal B, Sripan P, Urien S, et al · · 2020 · cited 6× · PMID 32205720 · DOI 10.1097/qai.0000000000002350