NCT02140255

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 1,120 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 48 Hours
• Healthy volunteers: Not accepted

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. 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.

Conditions

• HIV Infection

Interventions

Type	Name	Description
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.
DRUG	Raltegravir (RAL)	Administered orally. Dosed according to study step and participant's age.
DRUG	VRC01	40 mg/kg administered subcutaneously.
DRUG	Dolutegravir (DTG)	Dosed according to study step/participant's age/participant's weight
DRUG	VRC07-523LS	40 mg/kg administered subcutaneously.

Timeline

• Start date: 2015-01-23
• Primary completion: 2028-01-31
• Completion: 2031-12-31
• First posted: 2014-05-16
• Last updated: 2026-04-03

Locations

46 sites across 13 countries: United States, Argentina, Brazil, Haiti, Kenya, Malawi, Puerto Rico, South Africa, Tanzania, Thailand, Uganda, Zambia, Zimbabwe

Regulatory

• FDA-regulated drug study