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HIVPhase 2/3EITNCT02369406

Early Infant HIV Treatment in Botswana

A Phase 2/3 study testing Nevirapine, Kaletra and Lamivudine in people with HIV and Pediatric AIDS, run by Harvard School of Public Health (HSPH) at 1 site in Botswana.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 0 days to 3 years
Conditions the study is for
HIV, Pediatric AIDS
What is being tested?
Nevirapine, Kaletra and Lamivudine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
1 siteBotswana
Study dates
4 May 2015to 30 Jun 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 days to 3 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 34Show fewer
  • 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.
  • 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.
  • 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
  • Eligible for ART through the Botswana government program
  • Ability to be followed in BHP clinic for ART for up to 240 weeks after enrollment#
  • 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.
  • Mother/guardian ≥18 years of age and able to provide informed consent
  • 24-36 months of age
  • HIV-infection documented within 365 days after birth
  • 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.
  • After 6 months of ART, no more than one HIV RNA measurement > 400 copies/mL
  • Exclusion Criteria (for antepartum and peripartum infection cohort):
  • 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.

Who cannot join

  • 1) < 85% reported adherence to prescribed doses or interruption of ART for more than 7 consecutive days since its initiation.

Trial locations and contacts

1 site in 1 country.

Botswana1 site

  • Botswana Harvard HIV/AIDS Institute Partnership

    Gaborone

Other trials in Botswana

About this study

Official title: BHP Early Infant Treatment Study: A Clinical Treatment Trial of HIV+ Infants in Botswana

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.

Read the detailed description

HIV-1 infection during adulthood leads to a stable, long-lasting viral reservoir in CD4 T cells that persists despite suppressive antiretroviral therapy (ART), and is responsible for rapid viral rebound once treatment is stopped in most cases. In neonates, HIV-1 infection occurs at a time when the adaptive immune system is still in development, which may alter the establishment of a long-lasting viral reservoir and offer opportunities to reduce viral persistence through early antiretroviral treatment. Recently, scientific understanding of neonatal HIV infection has been challenged by the description of an infant who tested positive for HIV at birth, was treated with potent combination antiretroviral therapy (ART) within the first 30 hours of life, and achieved long-term remission of HIV infection when ART was stopped approximately 18 months later. Unfortunately, after 2 years off ART, rebound viremia occurred in this child, yet this case raises the provocative question of whether ART initiated within the first days of life for an antepartum infection, or in the first days/weeks of life for a peripartum infection, can prevent the seeding of a long-lasting reservoir of HIV infected cells in some infants (and therefore lead to long periods of HIV remission off ART).

Conditions
HIV, Pediatric AIDS
Being tested
Nevirapine, Kaletra, Lamivudine, Zidovudine
Keywords
Botswana, Immunology, Antiretroviral Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NevirapineDrug

    Also called NVP

  • KaletraDrug

    Also called LPV/r

  • LamivudineDrug

    Also called 3TC

  • ZidovudineDrug

    Also called ZDV

Study groups in NCT02369406
Study groupRoleWhat they receive
Antepartum CohortExperimental40 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.
Receives: Drug: Nevirapine; Drug: Kaletra; Drug: Lamivudine; Drug: Zidovudine
Peripartum CohortExperimental10 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.
Receives: Drug: Nevirapine; Drug: Kaletra; Drug: Lamivudine; Drug: Zidovudine
Control CohortNo intervention25 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 14 days

  2. 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

    Measured: 14 days

  3. 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)

    Measured: 14 days

  4. 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.

    Measured: 84-96 weeks

Secondary outcomes (3)

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

    Measured: up to 576 weeks

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

    Threshold of detection is expected to be approximately 5 copies/million PBMCs, but varies by sample volume available.

    Measured: up to 576 weeks

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

    Measured: up to 576 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2015 (estimated)
  2. Study start4 May 2015
  3. Primary completion6 Nov 2020
  4. Study completion30 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02369406
Sponsor's protocol ID
U01AI114235
Acronym
EIT
Status last verified
Feb 2026
First submitted
12 Feb 2015
Last updated
23 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 35858580

  • 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.

    PubMed 29852062

  • 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.

    PubMed 31927562

  • 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.

    PubMed 31776292

  • 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.

    PubMed 33605999

  • 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.

    PubMed 32287064

  • 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.

    PubMed 32195745

  • 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.

    PubMed 34324451

  • 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.

    PubMed 28350554

  • 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.

    PubMed 37201510

  • 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.

    PubMed 36729692

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Nevirapine, Kaletra and Lamivudine in people with HIV and Pediatric AIDS, run by Harvard School of Public Health (HSPH) at 1 site in Botswana.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Botswana. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the proportion of infants who have treatment-limiting adverse events within the first 14 days of treatment (time frame: 14 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02369406, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.

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