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| ID | Type | Description | Link |
|---|---|---|---|
| U01HD080441 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| University of Witwatersrand, South Africa | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of patients with initial viral suppression | Suppression is defined as patients with plasma HIV RNA <50 copies/mL. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of patients maintaining viral suppression | Suppression is defined as patients with plasma HIV RNA <50 copies/mL. | Between 24 and104 weeks |
| Prevalence of CD4 percentage greater than 30 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Louise Kuhn, PhD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rahima Moosa Mother and Child Hospital | Johannesburg | Gauteng | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38508485 | Derived | Barrios-Tascon A, Strehlau R, Patel F, Burke M, Shiau S, Shen Y, Arpadi SM, Abrams EJ, Tiemessen CT, Kuhn L; LEOPARD study team. Growth Trajectories Over the First Year of Life Among Early-Treated Infants with Human Immunodeficiency Virus and Infants Who are Human Immunodeficiency Virus-Exposed Uninfected. J Pediatr. 2024 Jul;270:114018. doi: 10.1016/j.jpeds.2024.114018. Epub 2024 Mar 19. | |
| 34185838 | Derived | 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. |
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Contact PI Non-identifying data
Based on availability of resources
Scientific justification
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| ID | Term |
|---|---|
| D019829 | Nevirapine |
| D015215 | Zidovudine |
| D019259 | Lamivudine |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013936 | Thymidine |
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| 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. |
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| 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. |
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| 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. |
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Patients that reached a normal CD4% level.
| By 24 weeks and sustained through 104 weeks |
| Prevalence of growth along curve within one standard deviation or upward trend | By comparing viral growth curves. | Up to 104 weeks |
| Prevalence of detection of specific HIV antibody classes | HIV antibody detection | 24 and 104 weeks |
| Size of the viral reservoir (copies/million cell) | Quantification of viral reservoir | Up to 104 weeks |
| 31993578 | 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. |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D015224 | Dideoxynucleosides |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D016047 | Zalcitabine |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |