Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial

NCT02431975 | Completed Phase 4 DMC

• 2 other identifiers: AAAO5011U01HD080441
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose a non-randomized clinical trial of 60 HIV-infected infants identified within 48 hours of birth and their mothers to investigate the consequences of very early ART on the establishment and maintenance of the viral reservoir. The first phase (early ART initiation within 48 hours of birth) will examine the trajectory i.e. changes over time of the viral reservoir and detection of HIV-specific antibody responses in infants testing HIV-positive within 48 hours of birth and initiating early ART. Secondary pathogenesis aims will test whether markers of neonatal immune quiescence are associated with the extent of seeding and rate of decline of the viral reservoir when ART is started at a young age and investigate whether markers in infant stool samples can be used as a non-invasive method of defining relevant immune and HIV-specific parameters associated with viral reservoir size. The investigators hypothesize that developmental characteristics of newborn immunity may make this period the optimal time to begin ART and influence the seeding of the viral reservoir.

Conditions

HIV

Keywords

HIV; infant; antiretroviral therapy, highly active; antiretroviral agents

Outcome Measures

Primary Outcomes (1)

• Percent of patients with initial viral suppression

  Suppression is defined as patients with plasma HIV RNA \<50 copies/mL.

  24 weeks

Secondary Outcomes (5)

• Percent of patients maintaining viral suppression

  Between 24 and104 weeks

• Prevalence of CD4 percentage greater than 30

  By 24 weeks and sustained through 104 weeks

• Prevalence of growth along curve within one standard deviation or upward trend

  Up to 104 weeks

• Prevalence of detection of specific HIV antibody classes

  24 and 104 weeks

• Size of the viral reservoir (copies/million cell)

  Up to 104 weeks

Study Arms (1)

Early ART

EXPERIMENTAL

All infants enrolled in the trial, regardless of maternal PMTCT regimen, will be initiated on a triple ARV regimen consisting of nevirapine (NVP), zidovudine (ZDV) and lamivudine (3TC) presumptively based on the initial positive result. This regimen will be continued to 42 weeks post menstrual age (PMA). At this time, infants will be switched to LPV/r, ZDV and 3TC to be continued to 104 weeks or longer unless otherwise preferred by the treating clinician or if any clinical or laboratory contraindications are identified.

Drug: Nevirapine; Drug: Zidovudine; Drug: Lamivudine; Drug: LPV/r

Interventions

Nevirapine DRUG

Standard medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medication. The initial dose of NVP will be 6 mg per kg per dose orally twice daily until 42 weeks gestational age (2 weeks of age for infants born at term) which is the dosing selected by the NIH International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network.

Also known as: NVP, Viramune

Early ART

Zidovudine DRUG

An antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretroviral. ZDV will be dosed as per standard guideline and routine practices.

Also known as: ZDV, Retrovir

Early ART

Lamivudine DRUG

An antiretroviral medication used to prevent and treat HIV/AIDS. It is effective against both HIV-1 and HIV-2. 3TC will be dosed as per standard guideline and routine practices.

Also known as: 3TC, Epivir

Early ART

LPV/r DRUG

Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir. LPV/r will be dosed as per standard guideline and routine practices.

Also known as: Ritonavir-boosted lopinavir

Early ART

Eligibility Criteria

• Age: Up to 48 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Point of care (POC) or laboratory-based test positive on a sample collected within 48 hours of birth.
• Mother willing and able to provide informed consent.

You may not qualify if:

• Expressed intention to leave the Johannesburg area permanently.
• Co-morbidities, birth defects or other conditions which in the opinion of the clinical team have a greater than 50% risk of mortality in the first days of life.
• Co-morbidities or conditions which in the opinion of the clinical team advise against initiation of ART within the first 48 hours of life.
• Active (uncontrolled) maternal psychiatric illness.

Sponsors & Collaborators

• Columbia University: lead
• National Institutes of Health (NIH): collaborator
• University of Witwatersrand, South Africa: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Rahima Moosa Mother and Child Hospital

Johannesburg, Gauteng, South Africa

Location

Related Publications (2)

• Kuhn L, Paximadis M, Da Costa Dias B, Shen Y, Mncube S, Strehlau R, Shiau S, Patel F, Burke M, Technau KG, Sherman G, Loubser S, Abrams EJ, Tiemessen CT. Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants. Clin Infect Dis. 2022 Mar 23;74(6):1047-1054. doi: 10.1093/cid/ciab586.

  PMID: 34185838 DERIVED

• Kuhn L, Strehlau R, Shiau S, Patel F, Shen Y, Technau KG, Burke M, Sherman G, Coovadia A, Aldrovandi GM, Hazra R, Tsai WY, Tiemessen CT, Abrams EJ; LEOPARD Study Team. Early antiretroviral treatment of infants to attain HIV remission. EClinicalMedicine. 2020 Jan 7;18:100241. doi: 10.1016/j.eclinm.2019.100241. eCollection 2020 Jan.

  PMID: 31993578 DERIVED

MeSH Terms

Interventions

Nevirapine; Zidovudine; Lamivudine

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine

Study Officials

• Louise Kuhn, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Epidemiology, Department of Epidemiology

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: May 1, 2015
• Study Start: August 1, 2015
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: August 4, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Based on availability of resources
• Access Criteria: Scientific justification

Locations

ZA (1)