Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission

Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission: A Phase I/II Proof of Concept Study

The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

Study Overview

• Status: Recruiting
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Lopinavir/Ritonavir (LPV/r); Drug: Raltegravir (RAL); Drug: VRC01; Drug: VRC07-523LS; Drug: Dolutegravir (DTG)

Detailed Description

The purpose of this study is to explore the effects of early intensive antiretroviral therapy (ART) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

The study will enroll two cohorts. Cohort 1 will include infants born to a mother with presumed or confirmed HIV infection who received no or very limited antiretrovirals during pregnancy. Cohort 2 will include infants with at least one positive HIV nucleic acid test result from a sample collected within 48 hours of birth who initiated a qualifying ART regimen within 48 hours of birth.

Seven early intensive therapy regimens will be assessed. Regimen 1L will include 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus nevirapine (NVP) plus lopinavir/ritonavir (LPV/r). Regimen 2R will include 2 NRTIs plus NVP plus raltegravir (RAL). Regimen 2RV will include 2 NRTIs plus NVP plus RAL plus VRC01 monoclonal antibody. Regimen 3RD will include 2 NRTIs plus NVP plus RAL with subsequent switch to 2 NRTIs plus dolutegravir (DTG) upon reaching 28 days of age and 3 kg body weight. Regimen 3RDV7 will include 2 NRTIs plus NVP plus RAL plus VRC07-523LS with subsequent switch to 2 NRTIs plus DTG plus VRC07-523LS upon reaching 28 days of age and 3 kg body weight. Regimen 4D will include 2 NRTIs plus DTG. Regimen 4DV7 will include 2 NRTIs plus DTG plus VRC07-523LS.

The study will be conducted in four steps. In Step 1, Cohort 1 infants will be enrolled for evaluation of HIV infection and initiation of early intensive therapy within 48 hours of birth. Infants in whom in utero HIV infection is excluded will switch from the study regimen to standard perinatal prophylaxis per local guidelines within two weeks; these infants will continue in Step 1 safety monitoring for two additional weeks, undergo HIV testing at approximately 24 weeks of age, and then exit the study. Infants in whom in utero HIV infection is confirmed will enter Step 2 at least two weeks after enrollment in Step 1.

In Step 2, infants will receive the study regimen for up to 192 weeks. Beginning at Step 2 Week 84, children who achieved HIV RNA suppression by Week 24, and maintained suppression, thereafter, will be evaluated for possible analytic treatment interruption (ATI).

In Step 3, children in Step 2 who meet criteria for ATI will interrupt ART and be closely monitored for viral rebound for up to five years.

In Step 4, children who experience viral rebound in Step 3 or meet other Step 4 inclusion criteria will re-initiate ART and be closely monitored for viral re-suppression on ART until five years of age or six months after re-suppression, whichever is later.

• Study Type: Interventional
• Enrollment (Estimated): 1120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Anne Coletti, MS; Phone Number: 919-627-6445; Email: acoletti@fhi360.org

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1221ADC
    • Withdrawn
    • Hosp. General de Agudos Buenos Aires Argentina NICHD CRS
• Brazil
  • Minas Gerais, Brazil, 30.130-100
    • Recruiting
    • 5073, School of Medicine Federal University Minas Gerais Clinical Research Site
    • Contact: Laura Costa; Phone Number: 55-31-3409-9822; Email: lavlc@hotmail.com
  • Rio de Janeiro, Brazil, 21941-612
    • Recruiting
    • 5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site
    • Contact: Lorena Pestana; Phone Number: 55-21-3148-2255; Email: lorena.pestana@gmail.com
  • Rio de Janeiro, Brazil, 26030
    • Recruiting
    • 5097, Hospital Geral de Nova Igaucu Clinical Research Site
    • Contact: Aline R Benevenuto; Phone Number: 55-22-996-107-788; Email: alineramalhopesquisa@gmail.com
  • Rio de Janeiro, Brazil, 20221-903
    • Completed
    • 5072, Hospital Federal dos Servidores do Estado Clinical Research Site
  • São Paulo, Brazil, 14049-900
    • Completed
    • 5074, University of Sao Paulo Clinical Research Site
  • Rio Greande Do Sul
    • Porto Alegre, Rio Greande Do Sul, Brazil, 91350-200
      • Completed
      • Hospital Nossa Senhora da Conceicao NICHD CRS
• Haiti
  • Port-au-Prince, Haiti, HT-6110
    • Recruiting
    • 30022, Les Centres GHESKIO Clinical Research Site
    • Contact: Jeffrey Celius; Phone Number: 509-3686-3317; Email: jeffrey.celius@gheskio.org
• Kenya
  • Kericho, Kenya, 20200
    • Recruiting
    • 5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center Kericho Clinical Research Site
    • Contact: David K. Wekulo; Phone Number: 254-729-110-146; Email: david.wekulo@usamru-k.org
• Malawi
  • Blantyre, Malawi
    • Recruiting
    • 30301, Blantyre Clinical Research Site
    • Contact: Hazzie Mvula; Phone Number: 265-884-55-30-91; Email: hmvula@jhp.mw
  • Central Region
    • Lilongwe, Central Region, Malawi
      • Recruiting
      • 12001, Malawi Clinical Research Site
      • Contact: Daphne N. Gadama; Phone Number: 265-99-929-8224; Email: dgadama@unclilongwe.org
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • Withdrawn
    • San Juan City Hosp. PR NICHD CRS
  • PR
    • San Juan, PR, Puerto Rico, 00935
      • Not yet recruiting
      • 32513, IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research Network CRS
      • Contact: Sylvia I Davila-Nieves, M.Sc.; Phone Number: 1-787-7679193; Email: sylvia.davila1@upr.edu
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Completed
      • Wits RHI Shandukani Research Centre CRS
    • Johannesburg, Gauteng, South Africa, 1862
      • Completed
      • Soweto IMPAACT CRS
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Recruiting
      • 30300, Umlazi Clinical Research Site
      • Contact: Zukiswa Godlwana; Phone Number: 27-31-260-1998; Email: zukiswa.godlwana@caprisa.org
  • Western Cape
    • Tygerberg, Western Cape, South Africa, 7505
      • Completed
      • 8950, FAMCRU Clinical Research Site
• Tanzania
  • Moshi, Tanzania
    • Recruiting
    • 5118, Kilimanjaro Christian Medical Centre Clinical Research Site
    • Contact: Winfrida Shirima; Phone Number: 255-765-309-411; Email: winshirima2015@gmail.com
• Thailand
  • Chiang Mai, Thailand, 50100
    • Recruiting
    • 5116, Chiangrai Prachanukroh Hospital Clinical Research Site
    • Contact: Pra-ornsuda Sukrakanchana; Phone Number: 66-81-7468858; Email: Pra-ornsuda.Sukrakanchana@phpt.org
  • Bangkoknoi
    • Bangkok, Bangkoknoi, Thailand, 10700
      • Recruiting
      • 5115, Siriraj Hospital Mahidol University Clinical Research Site
      • Contact: Watcharee Lermankul; Phone Number: 66-2-866-0225; Email: watcharee.ler@mahidol.edu
• Uganda
  • Kampala, Uganda
    • Completed
    • MU-JHU Care Limited CRS
  • Kampala, Uganda
    • Recruiting
    • 31798, Baylor-Uganda Clinical Research Site
    • Contact: Beatrice Nagaddya; Phone Number: 256-417-119-200; Email: bnagaddya@baylor-uganda.org
• United States
  • California
    • La Jolla, California, United States, 92093-0672
      • Completed
      • 4601, University of California, San Diego Clinical Research Site
    • Los Angeles, California, United States, 90089
      • Recruiting
      • 5048, University of Southern California Clinical Research Site
      • Contact: Yvonne A. Morales; Phone Number: 323-865-1561; Email: ytr@usc.edu
    • Los Angeles, California, United States, 90095-1752
      • Recruiting
      • 5112, David Geffen School of Medicine at UCLA Clinical Research Site
      • Contact: Margaret F. Bradley; Phone Number: 310-206-3895; Email: mabradley@mednet.ucla.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • 5052, University of Colorado, Denver Clinical Research Site
      • Contact: Carrie Chambers, RN; Phone Number: 720-777-4424; Email: carrie.chambers@childrenscolorado.org
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Completed
      • 5055, South Florida CDTC Fort Lauderdale Clinical Research Site
    • Jacksonville, Florida, United States, 32209
      • Recruiting
      • 5051, University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES) Clinical Research Site
      • Contact: Saniyyah Mahmoudi, A.R.N.P.; Phone Number: 904-244-5331; Email: saniyyah.mahmoudi@jax.ufl.edu
    • Miami, Florida, United States, 33136
      • Recruiting
      • 5127, Pediatric Perinatal HIV Clinical Research Site
      • Contact: Nicolette Gomez; Phone Number: 305-243-4447; Email: n.gomez8@umiami.edu
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Withdrawn
      • Emory University School of Medicine NICHD CRS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • 5083, Rush University Cook County Hospital Clinical Research Site
      • Contact: Maureen McNichols, R.N., M.S.N., C.C.R.C.; Phone Number: 847-501-0243; Email: maureen_e_mcnichols@rush.edu
    • Chicago, Illinois, United States, 60614-3393
      • Recruiting
      • 4001, Lurie Children's Hospital of Chicago Clinical Research Site
      • Contact: Lela Lartey; Phone Number: 312-227-6280; Email: elartey@luriechildrens.org
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • 5092, Johns Hopkins Clinical Research Site
      • Contact: Amanda Haines; Phone Number: 443-287-8888; Email: ahaines8@jhmi.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Withdrawn
      • Boston Medical Center Ped. HIV Program NICHD CRS
  • New York
    • Stony Brook, New York, United States, 11794
      • Withdrawn
      • 5040, SUNY Stony Brook Clinical Research Site
    • The Bronx, New York, United States, 10457
      • Recruiting
      • 5114, Bronx Lebanon Hospital Center Clinical Research Site
      • Contact: Martha Cavallo, A.N.P., C.R.N.P.; Phone Number: 1-718-960-1010; Email: mcavallo@bronxleb.org
    • The Bronx, New York, United States, 10461
      • Recruiting
      • 5013, Jacobi Medical Center Clinical Research Site
      • Contact: Marlene Burey, R.N., M.S.N., P.N.P.; Phone Number: 1-718-918-4783; Email: marlene.burey@nychhc.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 9104
      • Withdrawn
      • Philadelphia IMPAACT Unit CRS
  • Tennessee
    • Memphis, Tennessee, United States, 38105-3678
      • Recruiting
      • 6501, St Jude Children's Research Hospital Clinical Research Site
      • Contact: Julie Maier; Phone Number: 901-595-3078; Email: julie.maier@stjude.org
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • 5128, Baylor College of Medicine/Texas Children's Hospital Clinical Research Site
      • Contact: Alejandra Martinez; Phone Number: 832-824-1443; Email: aamarti8@texaschildrens.org
  • Washington
    • Seattle, Washington, United States, 98101
      • Withdrawn
      • Seattle Children's Research Institute CRS
    • Seattle, Washington, United States, 98195
      • Withdrawn
      • Univ. of Washington NICHD CRS
• Zambia
  • Lusaka, Zambia, 10101
    • Completed
    • George CRS
• Zimbabwe
  • Chitungwiza, Zimbabwe
    • Recruiting
    • 30303, Saint Mary's Clinical Research Site
    • Contact: Suzen Maonera, M.Sc., B.Sc., R.N.; Phone Number: 263-772-288160; Email: smaonera@uzchs-ctrc.org
  • Chitungwiza, Zimbabwe
    • Recruiting
    • 30306, Seke North Clinical Research Site
    • Contact: Patricia Mandima; Phone Number: 263-712-437-682; Email: pmandima@uz-ctrc.org
  • Harare, Zimbabwe
    • Recruiting
    • 31890, Harare Family Care Clinical Research Site
    • Contact: Sukunena J. Maturure, RGN; Phone Number: 263-772-753-375; Email: smatarure@uz-ctrc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: No

Description

Maternal Inclusion Criteria

1. Presumed or confirmed maternal HIV infection:

   • Mothers will be eligible to enroll with EITHER:

     • Presumed HIV infection defined as at least one positive rapid HIV antibody-based test result from a sample collected in the peripartum period. Presumed infection must be confirmed within 10 business days of enrollment OR
     • Confirmed HIV infection defined as positive results from two samples collected at different timepoints
2. Willing and able to provide written informed consent for participation of herself and her infant. The mother must be of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with IRB/EC policies and procedures. Otherwise, informed consent must be obtained from a legal guardian and the mother must provide written assent.
3. Was not previously enrolled in this study with another infant.
4. Did not receive ARVs during the current pregnancy.
5. Infant is eligible per inclusion criteria.

Infant Inclusion Criteria for Step 1

1. Less than or equal to 48 hours of age.
2. Greater than or equal to 37 weeks gestational age at birth (assessment of gestational age will be based on the best clinical estimate determined by date of last menstrual period, antenatal ultrasound, fundal height, or Ballard Score).
3. Greater than or equal to 2 kilograms (kg) at birth.
4. Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.
5. Has no clinically significant diseases (other than HIV infection) or clinically significant findings during review of medical history or physical examination prior to entry that, in the site investigator's opinion, would interfere with study participation or interpretation.
6. Mother is eligible per inclusion criteria.

Infant Inclusion Criteria for Step 2

1. Enrolled in Step 1.
2. Confirmed in utero HIV infection.
3. Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.
4. Has no clinically significant diseases (other than HIV infection) or clinically significant findings during review of medical history or physical examination prior to entry that, in the site investigator's opinion, would interfere with study participation or interpretation.
5. Mother (or legal guardian if applicable) is willing and able to provide written informed consent for child's participation in Step 2.

Infant Inclusion Criteria for Step 3

1. Enrolled in Step 2.
2. Has reached Step 2 Week 96.

3. Has the following results based on testing:

   • No confirmed plasma HIV RNA ≥200 copies/mL at Step 2 Week 24 and up to but excluding Step 2 Week 48.

   • No plasma HIV RNA detected at Step 2 Week 48 and thereafter, with two possible exceptions

     • (i) First possible exception: If HIV RNA is detected at or after Step 2 Week 48 with a result <200 copies/mL, testing will be repeated within three weeks (specimen collection for the confirmatory test must occur within three weeks of specimen collection for the initial test).
     • If no HIV RNA is detected on the confirmatory test, or if HIV RNA is detected with a result <200 copies/mL, the infant will be potentially eligible for Step 3 after an additional 48 weeks of follow-up in Step 2, provided no HIV RNA is detected on any subsequent tests in Step 2.
     • If HIV RNA is detected on the confirmatory test with a result ≥200 copies/mL, the infant will not be eligible for Step 3.
     • (ii) Second possible exception: If HIV RNA is detected after Step 2 Week 48 with a result <LOD, the infant will be potentially eligible for Step 3 after an additional 48 weeks of follow-up in Step 2 with no RNA detected. There is no limit on the number of times HIV RNA may be detected with a result <LOD after Week 48. However, infants with detectable RNA with a result <LOD after Week 48 will not be considered for entry into Step 3 until after an additional 48 weeks of no RNA detected.
     • Participants may experience either or both exceptions at different timepoints during follow-up in Step 2.
4. If breastfed, must have permanently ceased breastfeeding, with no exposure to breast milk for at least six weeks prior to specimen collection for the testing specified in the criterion (#5) below.

5. Has met ALL of the following additional criteria while in Step 2, based on testing between Step 2 Week 84 and Step 2 Week 192 (inclusive):

   • Two consecutive negative HIV antibody tests by fourth generation ELISA at least eight weeks apart.
   • Two consecutive HIV DNA tests with no DNA detected in at least 850,000 PBMCs assayed at least eight weeks apart.
   • CD4 cell percentage greater than or equal to 25% and CD4 cell absolute count greater than or equal to the lower limit of normal for age (≥1000 cells/mL if 2 to less than 3 years of age; ≥750 cells/mL if 3 to less than 5 years of age; ≥500 cells/mL if 5 years of age or older).
   • Infant assessed by the site investigator or designee as expected to adhere to the Step 3 Schedule of Evaluations.
   • Mother (or legal guardian if applicable) willing and able to provide written informed consent for child's participation in Step 3 and Step 4.
6. No plasma HIV RNA detected by testing after criteria have been confirmed, with specimen collection for the assay within 14 days prior to Step 3 Entry.

Infant Inclusion Criteria for Step 4

1. Enrolled in Step 3.

2. Has met at least one of the following:

   • Plasma HIV RNA ≥LOD based on two assays.
   • Plasma HIV RNA ≥1000 copies/mL in the presence of fever or other sign or symptom of acute retroviral syndrome.
   • Confirmed or suspected diagnosis of acute retroviral syndrome.
   • Confirmed or suspected diagnosis of a new WHO Clinical Stage 3 or 4 condition.
   • Confirmed CD4 cell percentage less than 25% and CD4 cell absolute count less than the lower limit of normal for age (<1000 cells/mL if 2 to less than 3 years of age; <750 cells/mL if 3 to less than 5 years of age; <500 cells/mL if 5 years of age or older).
   • Otherwise assessed by the site investigator or designee, in consultation with the Clinical Management Committee (CMC), as having an indication to re-initiate treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r; Participants will receive 2 NRTIs + NVP + LPV/r.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Lopinavir/Ritonavir (LPV/r); Administered orally. Dosed according to study step and participant's age.
Experimental: Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r; Participants will receive 2 NRTIs + NVP + LPV/r.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Lopinavir/Ritonavir (LPV/r); Administered orally. Dosed according to study step and participant's age.
Experimental: Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL; Participants will receive 2 NRTIs + NVP + RAL.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Raltegravir (RAL); Administered orally. Dosed according to study step and participant's age.
Experimental: Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL; Participants will receive 2 NRTIs + NVP + RAL.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Raltegravir (RAL); Administered orally. Dosed according to study step and participant's age.
Experimental: Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01; Participants will receive 2 NRTIs + NVP + RAL + VRC01.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Raltegravir (RAL); Administered orally. Dosed according to study step and participant's age.; Drug: VRC01; 40 mg/kg administered subcutaneously.
Experimental: Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG; Participants will receive 2 NRTIs + NVP + RAL with subsequent switch to 2 NRTIs + DTG upon reaching 28 days of age and 3 kg body weight.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Raltegravir (RAL); Administered orally. Dosed according to study step and participant's age.; Drug: Dolutegravir (DTG); Dosed according to study step/participant's age/participant's weight
Experimental: Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Participants will receive 2 NRTIs + NVP + RAL + VRC07-523LS with subsequent switch to 2 NRTIs + DTG + VRC07-523LS upon reaching 28 days of age and 3 kg body weight.	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Nevirapine (NVP); Administered orally. Dosed according to study step/participant's age/participant's weight.; Drug: Raltegravir (RAL); Administered orally. Dosed according to study step and participant's age.; Drug: VRC07-523LS; 40 mg/kg administered subcutaneously.; Drug: Dolutegravir (DTG); Dosed according to study step/participant's age/participant's weight
Experimental: Cohort 1, Regimen 4D: 2 NRTIs + DTG; Participants will receive 2 NRTIs + DTG	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: Dolutegravir (DTG); Dosed according to study step/participant's age/participant's weight
Experimental: Cohort 1, Regimen 4DV7: 2 NRTIs + DTG + VRC07-523LS; Participants will receive 2 NRTIs + DTG + VRC07-523LS	Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.; Drug: VRC07-523LS; 40 mg/kg administered subcutaneously.; Drug: Dolutegravir (DTG); Dosed according to study step/participant's age/participant's weight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who achieve HIV remission	Defined as no confirmed HIV RNA greater than or equal to the limit of detection (LOD) through 48 weeks of treatment interruption	Measured through Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with viral suppression to consistent HIV-1 RNA less than LOD	Based on laboratory evaluations	Measured through Week 24
Number of participants who experience HIV persistence	As measured by plasma viremia (single copy), droplet digital DNA, replication competent HIV reservoirs	Measured through Week 48
Frequency of Grade 3 or higher adverse events possibly, probably or definitely related to any component of the study regimen	Graded according to the DAIDS AE Grading Table, Corrected Version 2.1, dated July 2017	Measured through Week 192
Number of participants meeting all eligibility criteria for treatment interruption	As defined in criteria described in study protocol	Measured through Week 192
Number of infants meeting the selected eligibility criteria for treatment interruption among infants who also met the viral suppression criteria for treatment interruption.	As defined in criteria described in the study protocol	Measured through Week 192

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HIV-specific immune response	As measured by %CD8+/DR+ T cells	Measured through Week 48
Change in immune activation markers (%CD8+/DR+ T cells) response	As measured by HIV-specific antibodies and HIV-specific T cell responses	Measured through Week 48
Change in DTG concentration among treated neonates and young infants	Based on laboratory evaluations	Measured through Week 24
Change in VRC07-523LS concentration among treated neonates and young infants	Based on laboratory evaluations	Measured through Week 24
Presence of ARV genotypic resistance to drugs taken		Measured through Week 48
Presence of bNAb resistance as measured by inhibitory concentration		Measured through Week 48

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH)
• Investigators: Study Chair: Ellen Chadwick, MD, Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago; Study Chair: Jennifer Jao, MD, Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago

Publications and helpful links

General Publications

• Persaud D, Bryson Y, Nelson BS, Tierney C, Cotton MF, Coletti A, Jao J, Spector SA, Mirochnick M, Capparelli EV, Costello D, Szewczyk J, Nicodimus N, Stranix-Chibanda L, Kekitiinwa AR, Korutaro V, Reding C, Carrington MN, Majji S, Yin DE, Jean-Philippe P, Chadwick EG. HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study. Lancet HIV. 2024 Jan;11(1):e20-e30. doi: 10.1016/S2352-3018(23)00236-9. Epub 2023 Dec 4.
• Nelson BS, Tierney C, Persaud D, Jao J, Cotton MF, Bryson Y, Coletti A, Ruel TD, Spector SA, Reding C, Bacon K, Costello D, Perlowski C, Santos Cruz ML, Kosgei J, Majji S, Yin DE, Jean-Philippe P, Chadwick EG; IMPAACT P1115 Team. Infants Receiving Very Early Antiretroviral Therapy Have High CD4 Counts in the First Year of Life. Clin Infect Dis. 2023 Feb 8;76(3):e744-e747. doi: 10.1093/cid/ciac695.
• Ruel TD, Capparelli EV, Tierney C, Nelson BS, Coletti A, Bryson Y, Cotton MF, Spector SA, Mirochnick M, LeBlanc R, Reding C, Zimmer B, Persaud D, Bwakura-Dangarembizi M, Naidoo KL, Hazra R, Jean-Philippe P, Chadwick EG. Pharmacokinetics and safety of early nevirapine-based antiretroviral therapy for neonates at high risk for perinatal HIV infection: a phase 1/2 proof of concept study. Lancet HIV. 2021 Mar;8(3):e149-e157. doi: 10.1016/S2352-3018(20)30274-5. Epub 2020 Nov 23.
• Persaud D, Coletti A, Nelson BS, Jao J, Capparelli EV, Costello D, Tierney C, Kekitiinwa AR, Nematadzira T, Njau BN, Moye J, Jean-Philippe P, Korutaro V, Nalugo A, Mbengeranwa T, Chidemo T, Mmbaga BT, Sakasaka PA, Cotton M, Jennings C, Hoffmann C, Hovind L, Bryson Y, Chadwick EG; IMPAACT P1115 Study Team. ART-free HIV-1 remission in children with in-utero HIV-1 after very early ART (IMPAACT P1115): a multicentre, open-label, phase 1/2 proof-of-concept study. Lancet HIV. 2025 Nov;12(11):e743-e752. doi: 10.1016/S2352-3018(25)00189-4. Epub 2025 Sep 25.

Helpful Links

• Related Info
• ART-free HIV-1 remission in children with in-utero HIV-1 after very early ART (IMPAACT P1115): a multicentre, open-label, phase 1/2 proof-of-concept study

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2015
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimated): May 16, 2014

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HIV Remission
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrimidinones; Pyrrolidines; Pyrrolidinones; Raltegravir Potassium; Lopinavir; Nevirapine; dolutegravir
• Other Study ID Numbers: IMPAACT P1115; UM1AI068632 (U.S. NIH Grant/Contract); UM1AI068616 (U.S. NIH Grant/Contract); UM1AI106716 (U.S. NIH Grant/Contract); 11954 (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; 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