Intensive Antiretroviral Therapy for HIV/AIDS in Infants

Recruiting at 67 trial locations

Overseen By Anne Coletti, MS

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Disqualifiers: Significant diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

1120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on whether early, intensive treatment can help infants born with HIV achieve remission, where the virus remains undetectable. Researchers are testing various combinations of HIV medications, including Lopinavir/Ritonavir (Kaletra or Aluvia), Nevirapine, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and Raltegravir, along with a special antibody called VRC01, to determine the most effective approach. The trial seeks infants less than 48 hours old, born to mothers with HIV who did not receive treatment during pregnancy. The goal is to assess if these treatments can control the virus as the infants grow. As a Phase 1/Phase 2 trial, this research examines how the treatment works in people and measures its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking HIV treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications. It is best to consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of Nevirapine (NVP) and Raltegravir (RAL) is generally safe and well-tolerated. These drugs have a long history of use and are known for their safety. Raltegravir, for example, is considered safe, with only mild side effects reported in adults, children, and teenagers with HIV.

Studies have also shown that the combination involving VRC07-523LS is well-tolerated. This antibody is still under investigation, but early results regarding safety are promising.

Data from over 2,600 patients support the safety of Lopinavir/Ritonavir (LPV/r) combined with Nevirapine and other HIV drugs. This combination has been widely used and studied in various settings, including with pregnant women, demonstrating its general safety.

Overall, these treatments have been well-established and are known to be well-tolerated. No major safety concerns have been identified, making them a reasonable option for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HIV/AIDS in infants because they explore innovative combinations of antiretrovirals that could offer more effective early intervention. Some treatments in the trial combine standard nucleoside reverse transcriptase inhibitors (NRTIs) and nevirapine (NVP) with newer agents like raltegravir (RAL) and VRC01, which is a broadly neutralizing antibody. These combinations aim to enhance viral suppression and potentially reduce the risk of drug resistance. Notably, the inclusion of VRC01 and its variant VRC07-523LS, which target different HIV pathways, could provide additional immune system support beyond what traditional antiretroviral therapies offer. This innovative approach may lead to more effective management of HIV/AIDS in infants, particularly during the critical early stages of life.

What evidence suggests that this trial's treatments could be effective for HIV remission in infants?

Research has shown that antiretroviral therapy (ART) effectively manages HIV. In this trial, participants will receive different combinations of medications. Some will receive NRTIs, Nevirapine, and Raltegravir, which studies have found can lower HIV to undetectable levels in the blood. Others will receive Lopinavir/Ritonavir, which has also succeeded in many patients. Additionally, some participants will receive special antibodies, such as VRC01 or VRC07-523LS, which can further reduce the virus. Trials have shown that VRC07-523LS significantly lowers the amount of virus, making it a promising addition to early treatment. Overall, these combinations offer hope for effectively controlling HIV, especially when treatment begins early. ^{4 6 7 8 9}

Who Is on the Research Team?

Ellen Chadwick, MD

Principal Investigator

Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago

Jennifer Jao, MD

Principal Investigator

Northwestern University Feinberg School of Medicine and Ann & Robert Lurie Children's Hospital of Chicago

Are You a Good Fit for This Trial?

This trial is for HIV-infected infants born to mothers with confirmed or presumed HIV. Infants must be less than 48 hours old, at least 36 weeks gestational age, weigh over 2 kg, and able to take oral medication. Mothers should not have received antiretrovirals during pregnancy but may have during labor.

Inclusion Criteria

Infant eligible and enrolled in Cohort 1. No receipt of ARVs during the current pregnancy.

I am a mother with confirmed or presumed HIV, willing to consent for me and my infant.

Exclusion Criteria

Any 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 investigator's opinion, would interfere with study participation or interpretation.

I have had a condition where my lymphocytes grow abnormally.

Patient is living outside the US

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Early Intensive Treatment

Infants receive early intensive antiretroviral therapy (ART) within 48 hours of birth

192 weeks

Regular visits for monitoring and ART administration

Analytic Treatment Interruption (ATI)

Children who meet criteria interrupt ART and are monitored for viral rebound

Up to 5 years

Re-initiation of ART

Children who experience viral rebound or meet other criteria re-initiate ART and are monitored for re-suppression

Until 5 years of age or 6 months after re-suppression

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lopinavir/Ritonavir
• Nevirapine
• Nucleoside Reverse Transcriptase Inhibitors
• Raltegravir
• VRC01

Trial Overview The study tests early intensive antiretroviral therapy (ART) in newborns using drugs like Nevirapine, Lopinavir/Ritonavir, Raltegravir, VRC01 and NRTIs to see if it can induce HIV remission—meaning the virus becomes undetectable by standard tests.

How Is the Trial Designed?

Group I: Cohort 2, Regimen 2R: 2 NRTIs + NVP + RAL Experimental Treatment 3 Interventions

Participants will receive 2 NRTIs + NVP + RAL.

Group II: Cohort 2, Regimen 1L: 2 NRTIs + NVP + LPV/r Experimental Treatment 3 Interventions

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

Group III: Cohort 1, Regimen 3RDV7: 2 NRTIs + NVP + RAL + VRC07-523LS switch to 2 NRTIs + DTG + VRC07-523LS Experimental Treatment 4 Interventions

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.

Group IV: Cohort 1, Regimen 3RD: 2 NRTIs + NVP + RAL switch to 2 NRTIs + DTG Experimental Treatment 4 Interventions

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.

Group V: Cohort 1, Regimen 2RV: 2 NRTIs + NVP + RAL + VRC01 Experimental Treatment 4 Interventions

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

Group VI: Cohort 1, Regimen 2R: 2 NRTIs + NVP + RAL Experimental Treatment 3 Interventions

Participants will receive 2 NRTIs + NVP + RAL.

Group VII: Cohort 1, Regimen 1L: 2 NRTIs + NVP + LPV/r Experimental Treatment 3 Interventions

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

Lopinavir/Ritonavir is already approved in United States, European Union for the following indications:

Approved in United States as Kaletra for:

• HIV Infection
• Nonoccupational Exposure

Approved in European Union as Kaletra for:

• HIV Infection

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Raltegravir, now available in a chewable formulation, has been shown to effectively reduce HIV-1 RNA levels in treatment-experienced children and adolescents, with significant virologic improvements sustained for up to 48 weeks in a phase I/II clinical trial.

The treatment was generally well tolerated, and the new formulation allows for flexible dosing, making it a valuable option for managing HIV-1 in younger patients aged 2-18 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir: a review of its use in the management of HIV-1 infection in children and adolescents. Perry, CM.[2022]

Raltegravir is the first integrase inhibitor approved by the FDA for HIV-1 treatment, showing safety and efficacy in both treatment-naïve and treatment-experienced patients across numerous clinical studies.

The drug has milder adverse effects compared to older regimens and has favorable pharmacokinetics, making it a recommended option for HIV-1 treatment in newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir in HIV-1 infection: Safety and Efficacy in Treatment-naïve Patients. Pandey, KK.[2021]

The investigational NRTI- and RTV-sparing regimen of atazanavir (ATV) plus raltegravir (RAL) achieved a confirmed virologic response (CVR) of 74.6% at 24 weeks, which is comparable to the standard regimen of ATV with RTV and tenofovir/emtricitabine, indicating its potential efficacy for treatment-naïve HIV patients.

However, the ATV+RAL regimen was associated with a higher incidence of Grade 4 hyperbilirubinemia (20.6%) and developed resistance to RAL in some patients, suggesting safety concerns and limitations for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naïve HIV-infected patients: SPARTAN study results. Kozal, MJ., Lupo, S., DeJesus, E., et al.[2015]

In a study of 13 HIV-infected patients who underwent solid organ transplantation, the combination of raltegravir (RAL) and two nucleoside reverse transcriptase inhibitors (NRTIs) showed excellent tolerability and effectively controlled HIV infection without causing acute rejection of the transplanted organs.

All patients maintained satisfactory graft function and were alive after a median follow-up of 9 months, indicating that RAL is a promising alternative for managing HIV in patients receiving organ transplants, especially due to its lack of drug interactions with calcineurin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs. Tricot, L., Teicher, E., Peytavin, G., et al.[2023]

Raltegravir, an HIV-1 integrase inhibitor, was found to be safe and well tolerated in a study involving 52 full-term infants, with a specific dosing regimen established for the first 6 weeks of life.

The study successfully met pharmacokinetic exposure targets, indicating that the dosing regimen is effective for treating or preventing HIV in neonates, although it is not recommended for premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir (RAL) in Neonates: Dosing, Pharmacokinetics (PK), and Safety in HIV-1-Exposed Neonates at Risk of Infection (IMPAACT P1110). Clarke, DF., Acosta, EP., Cababasay, M., et al.[2022]

In three pediatric cases of HIV, rapid development of resistance to integrase strand transfer inhibitors (INSTIs) was observed due to poor treatment adherence and virological failure, highlighting the importance of monitoring adherence in young patients.

The study emphasizes that virological failure while on raltegravir necessitates an immediate change in antiretroviral therapy to prevent further mutations and resistance to newer INSTIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay. González Castro, AV., Sande, V., Pardo Casaretto, LV., et al.[2023]

Raltegravir (RAL) was safely and effectively used as a fourth HIV medication in two highly viraemic newborns, leading to significant reductions in plasma HIV-1 RNA levels within 28 days.

Both infants tolerated RAL well, with only one experiencing a temporary increase in gamma-glutamyltransferase, which normalized after stopping the medication, indicating that RAL can be a viable option for treating HIV in newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential role of raltegravir-based therapy to induce rapid viral decay in highly viraemic HIV-infected neonates. Ripamonti, D., Tatarelli, P., Mangili, G., et al.[2017]

Raltegravir is the first integrase inhibitor approved for treatment-experienced adults with HIV, showing strong efficacy in suppressing HIV-1 RNA levels for up to 48 weeks in clinical studies.

The drug is well tolerated and can be taken twice daily with or without food, making it a convenient option for patients with resistant HIV strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltegravir: the first in a new class of integrase inhibitors for the treatment of HIV. Sayana, S., Khanlou, H.[2015]

Citations

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KALETRA (lopinavir and ritonavir) Label - accessdata.fda.gov The safety of KALETRA has been investigated in about 2,600 patients in Phase II-IV clinical trials, of which about 700 have received a dose of 800/200 mg (6 ...

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