Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission
NCT ID: NCT02140255
Last Updated: 2025-09-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
1120 participants
INTERVENTIONAL
2015-01-23
2031-12-31
Brief Summary
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Detailed Description
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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.
Five 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.
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 final 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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r
Participants will receive 2 NRTIs + NVP + LPV/r.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Lopinavir/Ritonavir (LPV/r)
Administered orally. Dosed according to study step and participant's age.
Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r
Participants will receive 2 NRTIs + NVP + LPV/r.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Lopinavir/Ritonavir (LPV/r)
Administered orally. Dosed according to study step and participant's age.
Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL
Participants will receive 2 NRTIs + NVP + RAL.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL
Participants will receive 2 NRTIs + NVP + RAL.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01
Participants will receive 2 NRTIs + NVP + RAL + VRC01.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
VRC01
40 mg/kg administered subcutaneously.
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.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
DTG
Administered orally. Dosed according to participant's weight.
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.
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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
VRC07-523LS
40 mg/kg administered subcutaneously.
Interventions
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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.
Nevirapine (NVP)
Administered orally. Dosed according to study step/participant's age/participant's weight.
Lopinavir/Ritonavir (LPV/r)
Administered orally. Dosed according to study step and participant's age.
Raltegravir (RAL)
Administered orally. Dosed according to study step and participant's age.
VRC01
40 mg/kg administered subcutaneously.
DTG
Administered orally. Dosed according to participant's weight.
VRC07-523LS
40 mg/kg administered subcutaneously.
Eligibility Criteria
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Inclusion Criteria
* 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.
1. Less than or equal to 48 hours of age.
2. Greater than or equal to 36 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.
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.
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.
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.
48 Hours
ALL
No
Sponsors
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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
National Institute of Mental Health (NIMH)
NIH
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Ellen Chadwick, MD
Role: STUDY_CHAIR
Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago
Jennifer Jao, MD
Role: STUDY_CHAIR
Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago
Locations
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4601, University of California, San Diego Clinical Research Site
La Jolla, California, United States
5048, University of Southern California Clinical Research Site
Los Angeles, California, United States
5112, David Geffen School of Medicine at UCLA Clinical Research Site
Los Angeles, California, United States
5052, University of Colorado, Denver Clinical Research Site
Aurora, Colorado, United States
5055, South Florida CDTC Fort Lauderdale Clinical Research Site
Fort Lauderdale, Florida, United States
5051, University of Florida Center for HIV/AIDS Research, Education and Service (UF CARES) Clinical Research Site
Jacksonville, Florida, United States
5127, Pediatric Perinatal HIV Clinical Research Site
Miami, Florida, United States
University of Miami CRS
Miami, Florida, United States
Emory University School of Medicine NICHD CRS
Atlanta, Georgia, United States
5083, Rush University Cook County Hospital Clinical Research Site
Chicago, Illinois, United States
4001, Lurie Children's Hospital of Chicago Clinical Research Site
Chicago, Illinois, United States
5092, Johns Hopkins Clinical Research Site
Baltimore, Maryland, United States
Boston Medical Center Ped. HIV Program NICHD CRS
Boston, Massachusetts, United States
5040, SUNY Stony Brook Clinical Research Site
Stony Brook, New York, United States
5114, Bronx Lebanon Hospital Center Clinical Research Site
The Bronx, New York, United States
5013, Jacobi Medical Center Clinical Research Site
The Bronx, New York, United States
Philadelphia IMPAACT Unit CRS
Philadelphia, Pennsylvania, United States
6501, St Jude Children's Research Hospital Clinical Research Site
Memphis, Tennessee, United States
Texas Children's Hospital CRS
Houston, Texas, United States
5128, Baylor College of Medicine/Texas Children's Hospital Clinical Research Site
Houston, Texas, United States
Seattle Children's Research Institute CRS
Seattle, Washington, United States
Univ. of Washington NICHD CRS
Seattle, Washington, United States
Hosp. General de Agudos Buenos Aires Argentina NICHD CRS
Buenos Aires, , Argentina
Hospital Nossa Senhora da Conceicao NICHD CRS
Porto Alegre, Rio Greande Do Sul, Brazil
5073, School of Medicine Federal University Minas Gerais Clinical Research Site
Minas Gerais, , Brazil
5072, Hospital Federal dose Servidores do Estado Clinical Research Site
Rio de Janeiro, , Brazil
5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site
Rio de Janeiro, , Brazil
5097, Hospital Geral de Nova Igaucu Clinical Research Site
Rio de Janeiro, , Brazil
5074, University of Sao Paulo Clinical Research Site
São Paulo, , Brazil
30022, Les Centres GHESKIO Clinical Research Site
Port-au-Prince, , Haiti
5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center Kericho Clinical Research Site
Kericho, , Kenya
12001, Malawi Clinical Research Site
Lilongwe, Central Region, Malawi
30301, Blantyre Clinical Research Site
Blantyre, , Malawi
5129, University of Puerto Rico Gamma Project Clinical Research Site
San Juan, PR, Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, , Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, , Puerto Rico
Soweto IMPAACT CRS
Johannesburg, Gauteng, South Africa
Wits RHI Shandukani Research Centre CRS
Johannesburg, Gauteng, South Africa
30300, Umlazi Clinical Research Site
Durban, KwaZulu-Natal, South Africa
8950, FAMCRU Clinical Research Site
Tygerberg, Western Cape, South Africa
5118, Kilimanjaro Christian Medical Centre Clinical Research Site
Moshi, , Tanzania
5115, Siriraj Hospital Mahidol University Clinical Research Site
Bangkok, Bangkoknoi, Thailand
5116, Chiangrai Prachanukroh Hospital Clinical Research Site
Chiang Mai, , Thailand
31798, Baylor-Uganda Clinical Research Site
Kampala, , Uganda
MU-JHU Care Limited CRS
Kampala, , Uganda
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
Kampala, , Uganda
George CRS
Lusaka, , Zambia
30303, Saint Mary's Clinical Research Site
Chitungwiza, , Zimbabwe
30306, Seke North Clinical Research Site
Chitungwiza, , Zimbabwe
31890, Harare Family Care Clinical Research Site
Harare, , Zimbabwe
Countries
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Central Contacts
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Facility Contacts
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References
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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 Sep 24:S2352-3018(25)00189-4. doi: 10.1016/S2352-3018(25)00189-4. Online ahead of print.
Related Links
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Related Info
Other Identifiers
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11954
Identifier Type: REGISTRY
Identifier Source: secondary_id
IMPAACT P1115
Identifier Type: -
Identifier Source: org_study_id
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