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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Dolutegravir; Drug: Emtricitabine/tenofovir alafenamide; Drug: Emtricitabine/tenofovir disoproxil fumarate; Drug: Efavirenz/emtricitabine/tenofovir disoproxil fumarate

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 Type: Interventional
• Enrollment (Actual): 643
• Phase: Phase 3

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Molepolole CRS
  • South-East District
    • Gaborone, South-East District, Botswana
      • Gaborone CRS
• Brazil
  • Rio De Janeiro, Brazil, 20221-903
    • Hospital Federal dos Servidores do Estado NICHD CRS
  • Rio de Janeiro, Brazil, 21941-612
    • Instituto de Puericultura e Pediatria Martagao Gesteira - UFRJ NICHD CRS
  • Rio de Janeiro, Brazil, 26030
    • Hosp. Geral De Nova Igaucu Brazil NICHD CRS
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30.130-100
      • SOM Federal University Minas Gerais Brazil NICHD CRS
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411001
      • Byramjee Jeejeebhoy Medical College (BJMC) CRS
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1862
      • Soweto IMPAACT CRS
    • Johannesburg, Gauteng, South Africa, 2001
      • Wits RHI Shandukani Research Centre CRS
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4001
      • Umlazi CRS
  • Western Cape Province
    • Tygerberg, Western Cape Province, South Africa, 7505
      • Famcru Crs
• Tanzania
  • Moshi, Tanzania
    • Kilimanjaro Christian Medical Centre (KCMC)
• Thailand
  • Chiang Mai, Thailand, 50200
    • Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
  • Chiang Mai, Thailand, 50100
    • Chiangrai Prachanukroh Hospital NICHD CRS
  • Bangkoknoi
    • Bangkok, Bangkoknoi, Thailand, 10700
      • Siriraj Hospital ,Mahidol University NICHD CRS
• Uganda
  • Kampala, Uganda
    • Baylor-Uganda CRS
• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ. of Florida Jacksonville NICHD CRS
    • Miami, Florida, United States, 33136
      • Pediatric Perinatal HIV Clinical Trials Unit CRS
• Zimbabwe
  • Chitungwiza, Zimbabwe
    • St Mary's CRS
  • Chitungwiza, Zimbabwe
    • Seke North CRS
  • Harare, Zimbabwe
    • Harare Family Care CRS

Participation Criteria

Eligibility Criteria

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

Description

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
  • 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Maternal DTG+FTC/TAF; Mothers randomized to receive dolutegravir (DTG) plus emtricitabine/tenofovir alafenamide (FTC/TAF) during pregnancy, through delivery, and for 50 weeks postpartum.	Drug: Dolutegravir; One 50 mg DTG tablet was administered orally once daily; Other Names: DTG; Drug: Emtricitabine/tenofovir alafenamide; One fixed-dose combination tablet (FTC 200 mg/TAF 25 mg) was administered orally once daily; Other Names: FTC/TAF
Experimental: Arm 2: Maternal DTG+FTC/TDF; Mothers randomized to receive DTG plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum.	Drug: Dolutegravir; One 50 mg DTG tablet was administered orally once daily; Other Names: DTG; Drug: Emtricitabine/tenofovir disoproxil fumarate; One fixed-dose combination tablet (FTC 200 mg/TDF 300 mg) was administered orally once daily; Other Names: FTC/TDF
Active Comparator: Arm 3: Maternal EFV/FTC/TDF; Mothers randomized to receive efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) during pregnancy, through delivery, and for 50 weeks postpartum.	Drug: Efavirenz/emtricitabine/tenofovir disoproxil fumarate; One fixed-dose combination tablet (EFV 600 mg/FTC 200 mg/TDF 300 mg) was administered orally once daily; Other Names: EFV/FTC/TDF
No Intervention: Arm 1 Infants; 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.
No Intervention: Arm 2 Infants; 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.
No Intervention: Arm 3 Infants; 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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	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.	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.	From birth through Week 50 postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomization up to 74 weeks
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	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	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	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	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	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)	Delivery
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.	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.	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.	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.	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.	Birth through 50 weeks after birth
Maternal Change in Creatinine Clearance	Maternal change in creatinine clearance per week based on generalized estimating equations	Baseline to 50 weeks postpartum
Infant Creatinine Clearance	Infant creatinine clearance based on Schwartz formula	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.	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.	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	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	Birth
Change in Maternal Weight Antepartum	Change in maternal antepartum weight per week based on generalized estimating equations	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	Delivery to 50 weeks postpartum
Change in Maternal Weight Overall	Change in maternal weight per week based on generalized estimating equations	Baseline to 50 weeks postpartum

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Shahin Lockman, MD, MSc, Harvard T.H. Chan School of Public Health and Brigham and Women's Hospital; Study Chair: Lameck Chinula, MBBS, MMED, FCOG, Kamuzu Central Hospital in Lilongwe, Malawi

Publications and helpful links

General 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.

Helpful Links

• Study website
• 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 used
• Intergrowth 21st Standards, including reference for infants small for gestational age
• FDA Snapshot algorithm
• Definition for major congenital anomalies
• Schwartz formula for calculating infant creatinine clearance

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2018
• Primary Completion (Actual): October 3, 2020
• Study Completion (Actual): October 3, 2020

Study Registration Dates

• First Submitted: February 7, 2017
• First Submitted That Met QC Criteria: February 7, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz; Dolutegravir; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: IMPAACT 2010; 30129 (Registry Identifier: DAIDS-ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH
• IPD Sharing Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.; For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.; By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No