Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission
- Conditions
- HIV Infection
- Interventions
- Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs)Drug: Nevirapine (NVP)Drug: Raltegravir (RAL)Drug: Lopinavir/Ritonavir (LPV/r)Drug: VRC01Drug: DTGDrug: VRC07-523LS
- Registration Number
- NCT02140255
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1120
Not provided
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 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. 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.
- 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)
5040, SUNY Stony Brook Clinical Research Site
🇺🇸Stony Brook, New York, United States
5112, David Geffen School of Medicine at UCLA Clinical Research Site
🇺🇸Los Angeles, California, United States
4001, Lurie Children's Hospital of Chicago Clinical Research Site
🇺🇸Chicago, Illinois, United States
Boston Medical Center Ped. HIV Program NICHD CRS
🇺🇸Boston, Massachusetts, United States
5128, Baylor College of Medicine/Texas Children's Hospital Clinical Research Site
🇺🇸Houston, Texas, United States
Univ. of Washington NICHD CRS
🇺🇸Seattle, Washington, United States
5127, Pediatric Perinatal HIV Clinical Research Site
🇺🇸Miami, Florida, United States
University of Miami CRS
🇺🇸Miami, Florida, United States
31798, Baylor-Uganda Clinical Research Site
🇺🇬Kampala, Uganda
30301, Blantyre Clinical Research Site
🇲🇼Blantyre, Malawi
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
🇺🇬Kampala, Uganda
12001, Malawi Clinical Research Site
🇲🇼Lilongwe, Central, Malawi
8950, FAMCRU Clinical Research Site
🇿🇦Tygerberg, Western Cape, South Africa
30306, Seke North Clinical Research Site
🇿🇼Chitungwiza, Zimbabwe
George CRS
🇿🇲Lusaka, Zambia
5116, Chiangrai Prachanukroh Hospital Clinical Research Site
🇹ðŸ‡Chiang Mai, Thailand
5118, Kilimanjaro Christian Medical Centre Clinical Research Site
🇹🇿Moshi, Tanzania
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
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
Seattle Children's Research Institute CRS
🇺🇸Seattle, Washington, United States
Hosp. General de Agudos Buenos Aires Argentina NICHD CRS
🇦🇷Buenos Aires, Argentina
5072, Hospital Federal dose Servidores do Estado Clinical Research Site
🇧🇷Rio De Janeiro, Brazil
5074, University of Sao Paulo Clinical Research Site
🇧🇷São Paulo, Brazil
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
🇵🇷San Juan, Puerto Rico
MU-JHU Care Limited CRS
🇺🇬Kampala, Uganda
30303, Saint Mary's Clinical Research Site
🇿🇼Chitungwiza, Zimbabwe
Emory University School of Medicine NICHD CRS
🇺🇸Atlanta, Georgia, United States
5083, Rush University Cook County Hospital Clinical Research Site
🇺🇸Chicago, Illinois, United States
6501, St Jude Children's Research Hospital Clinical Research Site
🇺🇸Memphis, Tennessee, United States
5092, Johns Hopkins Clinical Research Site
🇺🇸Baltimore, Maryland, United States
Philadelphia IMPAACT Unit CRS
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital CRS
🇺🇸Houston, Texas, United States
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
5097, Hospital Geral de Nova Igaucu Clinical Research Site
🇧🇷Rio De Janeiro, Brazil
5121, Kenya Medical Research Institute/Walter Reed Project Clinical Research Center Kericho Clinical Research Site
🇰🇪Kericho, Kenya
30022, Les Centres GHESKIO Clinical Research Site
ðŸ‡ðŸ‡¹Port-au-Prince, Haiti
5129, University of Puerto Rico Gamma Project Clinical Research Site
🇵🇷San Juan, Puerto Rico
San Juan City Hosp. PR NICHD CRS
🇵🇷San Juan, Puerto Rico
Soweto IMPAACT CRS
🇿🇦Johannesburg, Gauteng, South Africa
30300, Umlazi Clinical Research Site
🇿🇦Durban, Kwa Zulu Natal, South Africa
5115, Siriraj Hospital Mahidol University Clinical Research Site
🇹ðŸ‡Bankok, Bangkoknoi, Thailand
31890, Harare Family Care Clinical Research Site
🇿🇼Harare, Zimbabwe
5071, Instituto de Puericultura e Pediatria Martagao Gesteira Clinical Research Site
🇧🇷Rio De Janeiro, Brazil
Wits RHI Shandukani Research Centre CRS
🇿🇦Johannesburg, Gauteng, South Africa
5052, University of Colorado, Denver Clinical Research Site
🇺🇸Aurora, Colorado, United States
5114, Bronx Lebanon Hospital Center Clinical Research Site
🇺🇸Bronx, New York, United States
5013, Jacobi Medical Center Clinical Research Site
🇺🇸Bronx, New York, United States