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

NCT02140255 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: IMPAACT P1115UM1AI068632UM1AI068616UM1AI10671611954
• Study Type: interventional
• Target: 1,120
• Locations: 12 countries
• Sites: 42

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV Remission

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Frequency of Grade 3 or higher adverse events possibly, probably or definitely related to any component of the study regimen

  Measured through Week 192

• Number of participants with viral suppression to consistent HIV-1 RNA less than LOD

  Measured through Week 24

• Number of participants meeting all eligibility criteria for treatment interruption

  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.

  Measured through Week 192

• Number of participants who experience HIV persistence

  Measured through Week 48

Other Outcomes (6)

• Change in HIV-specific immune response

  Measured through Week 48

• Change in immune activation markers (%CD8+/DR+ T cells) response

  Measured through Week 48

• Change in DTG concentration among treated neonates and young infants

  Measured through Week 24

Study Arms (9)

Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r

EXPERIMENTAL

Participants will receive 2 NRTIs + NVP + LPV/r.

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Lopinavir/Ritonavir (LPV/r)

Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r

EXPERIMENTAL

Participants will receive 2 NRTIs + NVP + LPV/r.

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Lopinavir/Ritonavir (LPV/r)

Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL

EXPERIMENTAL

Participants will receive 2 NRTIs + NVP + RAL.

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Raltegravir (RAL)

Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL

EXPERIMENTAL

Participants will receive 2 NRTIs + NVP + RAL.

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Raltegravir (RAL)

Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01

EXPERIMENTAL

Participants will receive 2 NRTIs + NVP + RAL + VRC01.

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Nevirapine (NVP); Drug: Raltegravir (RAL); Drug: VRC01

Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG

EXPERIMENTAL

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); Drug: Nevirapine (NVP); Drug: Raltegravir (RAL); Drug: Dolutegravir (DTG)

Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS

EXPERIMENTAL

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); Drug: Nevirapine (NVP); Drug: Raltegravir (RAL); Drug: Dolutegravir (DTG); Drug: VRC07-523LS

Cohort 1, Regimen 4D: 2 NRTIs + DTG

EXPERIMENTAL

Participants will receive 2 NRTIs + DTG

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Dolutegravir (DTG)

Cohort 1, Regimen 4DV7: 2 NRTIs + DTG + VRC07-523LS

EXPERIMENTAL

Participants will receive 2 NRTIs + DTG + VRC07-523LS

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Drug: Dolutegravir (DTG); Drug: VRC07-523LS

Interventions

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) DRUG

Chosen by the site investigator and dosed according to World Health Organization (WHO) or individual country or local standard guidelines.

Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r; Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL; Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01; Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG; Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Cohort 1, Regimen 4D: 2 NRTIs + DTG; Cohort 1, Regimen 4DV7: 2 NRTIs + DTG + VRC07-523LS; Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r; Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL

Nevirapine (NVP) DRUG

Administered orally. Dosed according to study step/participant's age/participant's weight.

Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r; Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL; Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01; Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG; Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r; Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL

Lopinavir/Ritonavir (LPV/r) DRUG

Administered orally. Dosed according to study step and participant's age.

Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r; Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r

Raltegravir (RAL) DRUG

Administered orally. Dosed according to study step and participant's age.

Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL; Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01; Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG; Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL

VRC01 DRUG

40 mg/kg administered subcutaneously.

Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01

VRC07-523LS DRUG

40 mg/kg administered subcutaneously.

Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Cohort 1, Regimen 4DV7: 2 NRTIs + DTG + VRC07-523LS

Dolutegravir (DTG) DRUG

Dosed according to study step/participant's age/participant's weight

Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG; Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS; Cohort 1, Regimen 4D: 2 NRTIs + DTG; Cohort 1, Regimen 4DV7: 2 NRTIs + DTG + VRC07-523LS

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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.
• Was not previously enrolled in this study with another infant.
• Did not receive ARVs during the current pregnancy.
• Less than or equal to 48 hours of age.
• 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).
• Greater than or equal to 2 kilograms (kg) at birth.
• Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.
• 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.
• Enrolled in Step 1.
• Confirmed in utero HIV infection.
• Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (46)

4601, University of California, San Diego Clinical Research Site

La Jolla, California, 92093-0672, United States

COMPLETED

5048, University of Southern California Clinical Research Site

Los Angeles, California, 90089, United States

RECRUITING

5112, David Geffen School of Medicine at UCLA Clinical Research Site

Los Angeles, California, 90095-1752, United States

RECRUITING

5052, University of Colorado, Denver Clinical Research Site

Aurora, Colorado, 80045, United States

RECRUITING

5055, South Florida CDTC Fort Lauderdale Clinical Research Site

Fort Lauderdale, Florida, 33316, United States

COMPLETED

5051, University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES) Clinical Research Site

Jacksonville, Florida, 32209, United States

RECRUITING

5127, Pediatric Perinatal HIV Clinical Research Site

Miami, Florida, 33136, United States

RECRUITING

Emory University School of Medicine NICHD CRS

Atlanta, Georgia, 30322, United States

WITHDRAWN

5083, Rush University Cook County Hospital Clinical Research Site

Chicago, Illinois, 60612, United States

RECRUITING

4001, Lurie Children's Hospital of Chicago Clinical Research Site

Chicago, Illinois, 60614-3393, United States

RECRUITING

5092, Johns Hopkins Clinical Research Site

Baltimore, Maryland, 21287, United States

RECRUITING

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

WITHDRAWN

5040, SUNY Stony Brook Clinical Research Site

Stony Brook, New York, 11794, United States

WITHDRAWN

5114, Bronx Lebanon Hospital Center Clinical Research Site

The Bronx, New York, 10457, United States

RECRUITING

5013, Jacobi Medical Center Clinical Research Site

The Bronx, New York, 10461, United States

RECRUITING

Philadelphia IMPAACT Unit CRS

Philadelphia, Pennsylvania, 9104, United States

WITHDRAWN

6501, St Jude Children's Research Hospital Clinical Research Site

Memphis, Tennessee, 38105-3678, United States

RECRUITING

5128, Baylor College of Medicine/Texas Children's Hospital Clinical Research Site

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Research Institute CRS

Seattle, Washington, 98101, United States

WITHDRAWN

Univ. of Washington NICHD CRS

Seattle, Washington, 98195, United States

WITHDRAWN

Hosp. General de Agudos Buenos Aires Argentina NICHD CRS

Buenos Aires, C1221ADC, Argentina

WITHDRAWN

Hospital Nossa Senhora da Conceicao NICHD CRS

Porto Alegre, Rio Greande Do Sul, 91350-200, Brazil

COMPLETED

5073, School of Medicine Federal University Minas Gerais Clinical Research Site

Minas Gerais, 30.130-100, Brazil

RECRUITING

5072, Hospital Federal dos Servidores do Estado Clinical Research Site

Rio de Janeiro, 20221-903, Brazil

COMPLETED

5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site

Rio de Janeiro, 21941-612, Brazil

RECRUITING

5097, Hospital Geral de Nova Igaucu Clinical Research Site

Rio de Janeiro, 26030, Brazil

RECRUITING

5074, University of Sao Paulo Clinical Research Site

São Paulo, 14049-900, Brazil

COMPLETED

30022, Les Centres GHESKIO Clinical Research Site

Port-au-Prince, HT-6110, Haiti

RECRUITING

5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center Kericho Clinical Research Site

Kericho, 20200, Kenya

RECRUITING

12001, Malawi Clinical Research Site

Lilongwe, Central Region, Malawi

RECRUITING

30301, Blantyre Clinical Research Site

Blantyre, Malawi

RECRUITING

5129, University of Puerto Rico Gamma Project Clinical Research Site

San Juan, PR, 00935, Puerto Rico

RECRUITING

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

WITHDRAWN

Soweto IMPAACT CRS

Johannesburg, Gauteng, 1862, South Africa

COMPLETED

Wits RHI Shandukani Research Centre CRS

Johannesburg, Gauteng, 2001, South Africa

COMPLETED

30300, Umlazi Clinical Research Site

Durban, KwaZulu-Natal, 4001, South Africa

RECRUITING

8950, FAMCRU Clinical Research Site

Tygerberg, Western Cape, 7505, South Africa

COMPLETED

5118, Kilimanjaro Christian Medical Centre Clinical Research Site

Moshi, Tanzania

RECRUITING

5115, Siriraj Hospital Mahidol University Clinical Research Site

Bangkok, Bangkoknoi, 10700, Thailand

RECRUITING

5116, Chiangrai Prachanukroh Hospital Clinical Research Site

Chiang Mai, 50100, Thailand

RECRUITING

31798, Baylor-Uganda Clinical Research Site

Kampala, Uganda

RECRUITING

MU-JHU Care Limited CRS

Kampala, Uganda

COMPLETED

George CRS

Lusaka, 10101, Zambia

COMPLETED

30303, Saint Mary's Clinical Research Site

Chitungwiza, Zimbabwe

RECRUITING

30306, Seke North Clinical Research Site

Chitungwiza, Zimbabwe

RECRUITING

31890, Harare Family Care Clinical Research Site

Harare, Zimbabwe

RECRUITING

Related Publications (4)

• 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.

  PMID: 38061376 BACKGROUND

• 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.

  PMID: 36031390 BACKGROUND

• 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.

  PMID: 33242457 BACKGROUND

• 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.

  PMID: 41015049 BACKGROUND

Related 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

MeSH Terms

Conditions

HIV Infections

Interventions

Nevirapine; Lopinavir; Raltegravir Potassium; dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Pyrrolidinones; Pyrrolidines

Study Officials

• 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

  STUDY CHAIR

Central Study Contacts

Anne Coletti, MS

CONTACT

919-627-6445; acoletti@fhi360.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 16, 2014
• Study Start: January 23, 2015
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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.

Locations

MA (2); ZA (1); UG (2); TA (1); HA (1); KE (1); US (20); TH (2); BR (6); ZI (3); AR (1); PR (2)