Early Infant HIV Treatment in Botswana

NCT02369406 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: U01AI114235
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

The overall objective of this study is to determine whether very early antiretroviral treatment (ART) initiation in HIV-infected infants limits the seeding of viral reservoirs and maintains immune responses, potentially allowing future periods off ART.

Conditions

HIV; Pediatric AIDS

Keywords

Botswana; Immunology; Antiretroviral Therapy

Outcome Measures

Primary Outcomes (4)

• To determine the proportion of infants who have treatment-limiting adverse events within the first 14 days of treatment

  14 days

• To determine the proportion of infants who fail to achieve at least a 1.5 log10 copies/mL reduction in HIV-1 RNA by the 14th day of treatment

  14 days

• To determine the proportion of infants in the antepartum cohort with trough drug concentrations below defined therapeutic ranges at 7 and 14 days of treatment (trough concentrations will be evaluated for NVP, ZDV, 3TC)

  14 days

• To evaluate virologic and immunologic outcomes of very early ART in infancy

  Virologic outcomes after early ART: We will evaluate how the timing of HIV infection and the timing of ART initiation affect the size and composition of the viral reservoir over time. Immunologic outcomes after early ART: We will evaluate how immune activation and immune activity against HIV-1 contribute to the size and composition of the HIV-1 reservoir over time in infants treated early with suppressive ART. Control Group Comparisons. We will evaluate virologic and immunologic outcomes at a single time point in children for whom ART initiation was later than in the prospective cohorts, and compared with immunologic testing of stored specimens from HIV exposed uninfected and HIV unexposed children.

  84-96 weeks

Secondary Outcomes (3)

• Number of participants with HIV-1 RNA levels <40 copies/mL

  up to 576 weeks

• Number of participants with reservoir HIV-1 DNA (in copies/million peripheral blood mononuclear cells, PBMCs) below the level of detection for total virus

  up to 576 weeks

• Median CD4 cell count (cells/mm3) and 95% confidence intervals among participants

  up to 576 weeks

Study Arms (3)

Antepartum Cohort

EXPERIMENTAL

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.

Drug: Nevirapine; Drug: Kaletra; Drug: Lamivudine; Drug: Zidovudine

Peripartum Cohort

EXPERIMENTAL

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.

Drug: Nevirapine; Drug: Kaletra; Drug: Lamivudine; Drug: Zidovudine

Control Cohort

NO INTERVENTION

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.

Interventions

Nevirapine DRUG

Also known as: NVP

Antepartum Cohort; Peripartum Cohort

Kaletra DRUG

Also known as: LPV/r

Antepartum Cohort; Peripartum Cohort

Lamivudine DRUG

Also known as: 3TC

Antepartum Cohort; Peripartum Cohort

Zidovudine DRUG

Also known as: ZDV

Antepartum Cohort; Peripartum Cohort

Eligibility Criteria

• Age: 0 Days - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Mother/guardian ≥18 years of age and able to provide informed consent
• Gestational age at birth ≥35 weeks
• Birth weight ≥2000 grams
• Age is less than 7 days\*
• 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\*\*
• Ability to initiate ART within 7 days after birth
• Eligible for ART through the Botswana government program
• Ability to be followed in BHP clinic for up to 240 weeks from enrollment#
• 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.
• Mother/guardian ≥18 years of age and able to provide informed consent
• Age is greater than 4 days and less than 57 days
• 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
• 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\*\*
• Ability to initiate ART at enrollment

You may not qualify if:

• Hospitalization for life-threatening medical illness
• Medical condition making it unlikely that the infant will survive to 96 weeks
• 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.
• \) \< 85% reported adherence to prescribed doses or interruption of ART for more than 7 consecutive days since its initiation.

Sponsors & Collaborators

• Brigham and Women's Hospital: collaborator
• Botswana Harvard Health Partnership: collaborator
• University of California, San Diego: collaborator
• Harvard School of Public Health (HSPH): lead
• Ragon Institute of MGH, MIT and Harvard: collaborator

Study Sites (1)

Botswana Harvard HIV/AIDS Institute Partnership

Gaborone, Botswana

Location

Related Publications (11)

• 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.

  PMID: 35858580 RESULT

• 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.

  PMID: 29852062 RESULT

• 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.

  PMID: 31927562 RESULT

• 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.

  PMID: 31776292 RESULT

• 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.

  PMID: 33605999 RESULT

• Ajibola G, Moyo S, Mohammed T, Moseki S, Jack D, Sakoi M, Batlang O, Maswabi K, Bennett K, Hughes MD, Lockman S, Makhema JM, Lichterfeld M, Kuritzkes DR, Shapiro RL. HIV diagnostic algorithm requires confirmatory testing for initial indeterminate or positive screens in the first week of life. AIDS. 2020 Jun 1;34(7):1029-1035. doi: 10.1097/QAD.0000000000002532.

  PMID: 32287064 RESULT

• Davey S, Ajibola G, Maswabi K, Sakoi M, Bennett K, Hughes MD, Isaacson A, Diseko M, Zash R, Batlang O, Moyo S, Lockman S, Lichterfeld M, Kuritzkes DR, Makhema J, Shapiro R. Mother-to-Child HIV Transmission With In Utero Dolutegravir vs. Efavirenz in Botswana. J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):235-241. doi: 10.1097/QAI.0000000000002338.

  PMID: 32195745 RESULT

• 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.

  PMID: 34324451 RESULT

• 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.

  PMID: 28350554 RESULT

• 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.

  PMID: 37201510 RESULT

• 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.

  PMID: 36729692 RESULT

MeSH Terms

Interventions

Nevirapine; lopinavir-ritonavir drug combination; Lamivudine; Zidovudine

Intervention Hierarchy (Ancestors)

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

Study Officials

• Roger L Shapiro, MD, MPH

  Harvard School of Public Health (HSPH)

  PRINCIPAL INVESTIGATOR

• Daniel R. Kuritzkes, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Mathias Lichterfeld, MD, PhD

  Ragon Institute of MGH, MIT and Harvard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 12, 2015
• First Posted: February 24, 2015
• Study Start: May 4, 2015
• Primary Completion: November 6, 2020
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

BO (1)