Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2/PHASE3
67 participants
INTERVENTIONAL
2015-05-04
2029-06-30
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Antepartum Cohort
40 children who test HIV-positive within 96 hours after birth (antepartum HIV infection) and are able to initiate ART \< 7 days after birth. This cohort will include at least 15 children who start ART \< 3 days after birth.
All infants in the antepartum cohort will initiate ART with Nevirapine, Zidovudine, Lamivudine, and later switch to Kaletra, Zidovudine, Lamivudine.
Nevirapine
Kaletra
Lamivudine
Zidovudine
Peripartum Cohort
10 children who test HIV-negative within 96 hours after birth but test HIV-positive \<57 days after birth (peripartum HIV infection) and who are able to initiate ART \<57 days after birth. This cohort will include at least 10 children who start ART \< 21 days after birth.
The majority of infants in the peripartum cohort will be able to start Kaletra, Zidovudine, Lamivudine as their first regimen, but a minority may start Nevirapine, Zidovudine, Lamivudine and then switch to Kaletra, Zidovudine, Lamivudine.
Nevirapine
Kaletra
Lamivudine
Zidovudine
Control Cohort
25 HIV-infected children who initiated ART at later age ranges (30-365 days for antepartum infection, 57-365 days for peripartum infection or for those with unknown timing of infection) will be enrolled for a single visit that will occur between 24 and 36 months of age. These children will serve as a control group for virologic and immunologic comparisons with children in the prospective cohorts.
No interventions assigned to this group
Interventions
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Nevirapine
Kaletra
Lamivudine
Zidovudine
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Gestational age at birth ≥35 weeks
3. Birth weight ≥2000 grams
4. Age is less than 7 days\*
5. HIV-infection identified by testing conducted within 96 hours after birth NOTE: HIV-infection is defined as DNA PCR positive on at least one specimen, with confirmation specimen either positive or pending\*\*
6. Ability to initiate ART within 7 days after birth
7. Eligible for ART through the Botswana government program
8. Ability to be followed in BHP clinic for up to 240 weeks from enrollment#
9. Blood samples collected and submitted for real-time safety lab evaluations; results may be pending at the time of entry.
* At least half of infants in the antepartum cohort must be \< 3 days at enrollment, including 3 of the first 6 infants enrolled.
* Participants will be offered extended follow-up for up to 576 weeks. However, willingness to participate in optional extended follow-up is not an inclusion criterion.
1. Mother/guardian ≥18 years of age and able to provide informed consent
2. Age is greater than 4 days and less than 57 days
3. HIV-negative within 96 hours after birth NOTE: HIV-negative is defined as HIV-negative by DNA PCR on a single specimen or HIV-negative on 2 separate confirmatory specimens following a re-test of an HIV-positive sample
4. HIV-positive between 96 hours and 56 days after birth NOTE: DNA PCR positive on at least one specimen with confirmation specimen either positive or pending repeat draw or result\*\*
5. Ability to initiate ART at enrollment
6. Eligible for ART through the Botswana government program
7. Ability to be followed in BHP clinic for ART for up to 240 weeks after enrollment#
8. Blood samples collected and submitted for real-time safety lab evaluations (results may be pending at the time of entry).
* An enrolled infant later determined to be HIV uninfected by confirmatory testing will end participation in the study and this enrollment will not be counted against the total number of enrollments planned.
* Participants will be offered extended follow-up for up to 576 weeks. However, willingness to participate in optional extended follow-up is not an inclusion criterion.
1. Mother/guardian ≥18 years of age and able to provide informed consent
2. 24-36 months of age
3. HIV-infection documented within 365 days after birth
4. ART initiated within the following timeframe based on timing of HIV-infection diagnosis \> 30-365 days after birth if HIV-infection diagnosed within 96 hours after birth OR \> 57-365 days after birth if infant was HIV-negative based on testing performed within 96 hours after birth (or if unknown HIV status \< 96 hours from birth) and then found to be HIV-positive based on testing performed between 96 hours and 365 days after birth.
5. After 6 months of ART, no more than one HIV RNA measurement \> 400 copies/mL
Exclusion Criteria
2. Medical condition making it unlikely that the infant will survive to 96 weeks
3. If lab values are available prior to enrollment, the following Division of AIDS 2014 graded results, from samples collected within 7 days prior to entry without subsequent testing, will exclude an infant:
* Grade ≥3 ALT
* Grade ≥3 AST
* Grade ≥4 hemoglobin
Note: Baseline lab values may not be available at the time of ART start. However, as soon as these values are available (occasionally within \<24 hours), they will be used to make rapid treatment decisions. Neonates with baseline Grade 4 hemoglobin will be called immediately to have ZDV discontinued if the value is confirmed. Neonates with baseline Grade 3 or 4 ALT or AST will be called immediately to stop either NVP or LPV/r if the value is confirmed. Neonates who remain on ART may remain on study. Neonates who discontinue all ART for pre-ART laboratory abnormalities will not be counted against total enrollments.
1\) \< 85% reported adherence to prescribed doses or interruption of ART for more than 7 consecutive days since its initiation.
0 Days
3 Years
ALL
No
Sponsors
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Ragon Institute of MGH, MIT and Harvard
OTHER
Brigham and Women's Hospital
OTHER
Botswana Harvard Health Partnership
UNKNOWN
University of California, San Diego
OTHER
Harvard School of Public Health (HSPH)
OTHER
Responsible Party
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Roger Shapiro
Principal Investigator
Principal Investigators
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Roger L Shapiro, MD, MPH
Role: PRINCIPAL_INVESTIGATOR
Harvard School of Public Health (HSPH)
Daniel R. Kuritzkes, MD
Role: PRINCIPAL_INVESTIGATOR
Brigham and Women's Hospital
Mathias Lichterfeld, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Ragon Institute of MGH, MIT and Harvard
Locations
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Botswana Harvard HIV/AIDS Institute Partnership
Gaborone, , Botswana
Countries
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References
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Hartana CA, Garcia-Broncano P, Rassadkina Y, Lian X, Jiang C, Einkauf KB, Maswabi K, Ajibola G, Moyo S, Mohammed T, Maphorisa C, Makhema J, Yuki Y, Martin M, Bennett K, Jean-Philippe P, Viard M, Hughes MD, Powis KM, Carrington M, Lockman S, Gao C, Yu XG, Kuritzkes DR, Shapiro R, Lichterfeld M. Immune correlates of HIV-1 reservoir cell decline in early-treated infants. Cell Rep. 2022 Jul 19;40(3):111126. doi: 10.1016/j.celrep.2022.111126.
Ibrahim M, Maswabi K, Ajibola G, Moyo S, Hughes MD, Batlang O, Sakoi M, Auletta-Young C, Vaughan L, Lockman S, Jean-Philippe P, Yu X, Lichterfeld M, Kuritzkes DR, Makhema J, Shapiro RL. Targeted HIV testing at birth supported by low and predictable mother-to-child transmission risk in Botswana. J Int AIDS Soc. 2018 May;21(5):e25111. doi: 10.1002/jia2.25111.
Maswabi K, Ajibola G, Bennett K, Capparelli EV, Jean-Philippe P, Moyo S, Mohammed T, Batlang O, Sakoi M, Lockman S, Makhema J, Lichterfeld M, Kuritzkes DR, Hughes MD, Shapiro RL. Safety and Efficacy of Starting Antiretroviral Therapy in the First Week of Life. Clin Infect Dis. 2021 Feb 1;72(3):388-393. doi: 10.1093/cid/ciaa028.
Garcia-Broncano P, Maddali S, Einkauf KB, Jiang C, Gao C, Chevalier J, Chowdhury FZ, Maswabi K, Ajibola G, Moyo S, Mohammed T, Ncube T, Makhema J, Jean-Philippe P, Yu XG, Powis KM, Lockman S, Kuritzkes DR, Shapiro R, Lichterfeld M. Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile. Sci Transl Med. 2019 Nov 27;11(520):eaax7350. doi: 10.1126/scitranslmed.aax7350.
Ajibola G, Garcia-Broncano P, Maswabi K, Bennett K, Hughes MD, Moyo S, Mohammed T, Jean-Philippe P, Sakoi M, Batlang O, Lockman S, Makhema J, Kuritzkes DR, Lichterfeld M, Shapiro RL. Viral Reservoir in Early-Treated Human Immunodeficiency Virus-Infected Children and Markers for Sustained Viral Suppression. Clin Infect Dis. 2021 Aug 16;73(4):e997-e1003. doi: 10.1093/cid/ciab143.
Mistry R, Wilke R, Challiss RA. Modulation of NMDA effects on agonist-stimulated phosphoinositide turnover by memantine in neonatal rat cerebral cortex. Br J Pharmacol. 1995 Feb;114(4):797-804. doi: 10.1111/j.1476-5381.1995.tb13275.x.
Gribakin FG. [Peculiarities of transmission of the receptor signal in photoreceptors]. Zh Evol Biokhim Fiziol. 1981 Sep-Oct;17(5):498-502. Russian.
Helbing C, Gallimore C, Atkinson BG. Characterization of a Rana catesbeiana hsp30 gene and its expression in the liver of this amphibian during both spontaneous and thyroid hormone-induced metamorphosis. Dev Genet. 1996;18(3):223-33. doi: 10.1002/(SICI)1520-6408(1996)18:33.0.CO;2-B.
Ibrahim M, Moyo S, Mohammed T, Mupfumi L, Gaseitsiwe S, Maswabi K, Ajibola G, Gelman R, Batlang O, Sakoi M, Auletta-Young C, Makhema J, Lockman S, Shapiro RL. Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana. J Acquir Immune Defic Syndr. 2017 Aug 15;75(5):e128-e131. doi: 10.1097/QAI.0000000000001384.
Hartana CA, Broncano PG, Maswabi K, Ajibola G, Moyo S, Mohammed T, Maphorisa C, Makhema J, Powis KM, Lockman S, Burbelo PD, Gao C, Yu XG, Kuritzkes DR, Shapiro R, Lichterfeld M. Immune Modulation of HIV-1 Reservoir Size in Early-Treated Neonates. J Infect Dis. 2023 Aug 11;228(3):281-286. doi: 10.1093/infdis/jiad173.
Ajibola G, Maswabi K, Hughes MD, Bennett K, Pretorius-Holme M, Capparelli EV, Jean-Philippe P, Moyo S, Mohammed T, Batlang O, Sakoi M, Ricci L, Lockman S, Makhema J, Kuritzkes DR, Lichterfeld M, Shapiro RL. Brief Report: Long-Term Clinical, Immunologic, and Virologic Outcomes Among Early-Treated Children With HIV in Botswana: A Nonrandomized Controlled Clinical Trial. J Acquir Immune Defic Syndr. 2023 Apr 15;92(5):393-398. doi: 10.1097/QAI.0000000000003147.
Moraka NO, Garcia-Broncano P, Hu Z, Ajibola G, Bareng OT, Pretorius-Holme M, Maswabi K, Maphorisa C, Mohammed T, Gaseitsiwe S, VanZyl GU, Kuritzkes DR, Lichterfeld M, Moyo S, Shapiro RL. Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana. AIDS. 2021 Dec 1;35(15):2413-2421. doi: 10.1097/QAD.0000000000003041.
Other Identifiers
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