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

Phase 1

Recruiting

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

• Registration Number: NCT02140255
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

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.

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.

Study Timeline

• Study First Submitted: 2014-05-13
• Study First Submitted QC: 2014-05-14
• Study First Posted: 2014-05-16
• Study Start: 2015-01-23
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-03
• Last Update Posted: 2025-04-04
• Primary Completion: 2028-01-31
• Study Completion: 2031-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL	Raltegravir (RAL)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r	Lopinavir/Ritonavir (LPV/r)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r	Nevirapine (NVP)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r	Lopinavir/Ritonavir (LPV/r)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL	Nevirapine (NVP)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	Participants will receive 2 NRTIs + NVP + RAL + VRC01.
Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01	VRC01	Participants will receive 2 NRTIs + NVP + RAL + VRC01.
Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	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.
Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	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.
Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS	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.
Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS	Nevirapine (NVP)	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.
Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01	Raltegravir (RAL)	Participants will receive 2 NRTIs + NVP + RAL + VRC01.
Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r	Nevirapine (NVP)	Participants will receive 2 NRTIs + NVP + LPV/r.
Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL	Nevirapine (NVP)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL	Raltegravir (RAL)	Participants will receive 2 NRTIs + NVP + RAL.
Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01	Nevirapine (NVP)	Participants will receive 2 NRTIs + NVP + RAL + VRC01.
Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG	Nevirapine (NVP)	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.
Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG	Raltegravir (RAL)	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.
Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS	Raltegravir (RAL)	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.
Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (50)

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

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