Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial

NCT ID: NCT02431975

Last Updated: 2020-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2020-04-30

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.

Detailed Description

Prevention of mother-to-child transmission (PMTCT) programs using antiretrovirals (ARVs) have had tremendous success in sub-Saharan Africa. However, HIV transmission continues to occur because (1) implementation of PMTCT is incomplete and (2) ARV interventions are not 100% effective in blocking infection. Thus the challenge of providing treatment to HIV-infected children is far from over. The capacity of early ART treatment to favorably influence the viral reservoir and potentially lead to post-treatment cessation viral control needs to be described in the population of infants, and to identify useful public health strategies.

Conditions

HIV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early ART

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.

Group Type: EXPERIMENTAL

Nevirapine

Intervention Type: 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.

Zidovudine

Intervention Type: 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.

Lamivudine

Intervention Type: 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.

LPV/r

Intervention Type: 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.

Interventions

Nevirapine

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.

Intervention Type: DRUG

Zidovudine

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.

Intervention Type: DRUG

Lamivudine

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.

Intervention Type: DRUG

LPV/r

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.

Intervention Type: DRUG

Other Intervention Names

NVP; Viramune; ZDV; Retrovir; 3TC; Epivir; Ritonavir-boosted lopinavir

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Maximum Eligible Age: 48 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Louise Kuhn

Professor of Epidemiology, Department of Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Louise Kuhn, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Rahima Moosa Mother and Child Hospital

Johannesburg, Gauteng, South Africa

Countries

South Africa

References

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.

Reference Type: DERIVED

PMID: 34185838 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31993578 (View on PubMed)

Other Identifiers

U01HD080441

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAO5011

Identifier Type: -

Identifier Source: org_study_id