Evidence map›Paper›PMID 34324451›Full record

Trial reportAIDS (London, England)2021

Patterns of pretreatment drug resistance mutations of very early diagnosed and treated infants in Botswana.

Natasha Onalenna Moraka, Pilar Garcia-Broncano, Zixin Hu, Gbolahan Ajibola, Ontlametse T Bareng, Molly Pretorius-Holme, Kenneth Maswabi, Comfort Maphorisa, Terence Mohammed, Simani Gaseitsiwe and 5 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial
In one paragraph

Trial report in AIDS (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02369406 (BHP Early Infant Treatment Study), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02369406 phase2 / phase3active not recruitingnot on this map

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

TypeinterventionalSponsorHarvard School of Public Health (HSPH)Ran2015 to 2029Enrolled67ConditionsHIV, Pediatric AIDSArmsNevirapine, Kaletra, Lamivudine, Zidovudine
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 3 countries.

Natasha Onalenna MorakaBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Pilar Garcia-BroncanoRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
Zixin HuDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School.
Gbolahan AjibolaBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Ontlametse T BarengBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Molly Pretorius-HolmeDepartment of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health.
Kenneth MaswabiBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Comfort MaphorisaBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Terence MohammedBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Simani GaseitsiweBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Gert U VanZylDivision of Medical Virology, Stellenbosch University Tygerberg, Cape Town, South Africa.
Daniel R KuritzkesDivision of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School.
Mathias LichterfeldRagon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts.
Sikhulile MoyoBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Roger L ShapiroBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Botswana Harvard AIDS Institute Partnership · BWHarvard University · USBrigham and Women's Hospital · USRagon Institute of MGH, MIT and Harvard · USStellenbosch University · ZA

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SONIA JAIN · 1994 to 2026
$78.4M
Early Infant TreatmentU01AI114235 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI KURITZKES, DANIEL R., LICHTERFELD, MATHIAS · 2014 to 2020
$5.1M
Training in HIV Genomics, Treatment, and Cure Research in BotswanaD43TW009610 · FIC · THE BOTSWANA HARVARD HEALTH PARTNERSHIP · PI SHAHIN LOCKMAN, Joseph Moeketsi Makhema · 2013 to 2026
$4.4M
Expansion of research and mentoring to improve birth outcomes and treatment outcomes among HIV-affected children in BotswanaK24AI131924 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Roger L Shapiro · 2018 to 2026
$1.6M
FIC NIH HHS D43 TW009610NCATS NIH HHS UL1 TR001442NIAID NIH HHS K24 AI131924NIAID NIH HHS P30 AI036214NIAID NIH HHS U01 AI114235Wellcome Trust 107752/Z/15/Z
6 · The paper itself

Abstract

objectiveTo describe the occurrence of HIV drug resistance mutations (DRMs) in both intact and defective HIV-1 cell-associated DNA (HIV-1 CAD) among early-treated infants.

designThe Botswana EIT Study (ClinicalTrials.gov NCT02369406) initiated antiretroviral therapy (ART) in the first week of life and evaluated HIV-1 in plasma and peripheral blood mononuclear cells (PBMCs). METHODOLOGY: We analyzed 257 near-HIV-1 full-length sequences (nFLS) obtained by Illumina next-generation sequencing from infants near birth. Sanger sequencing of pol was performed for mothers at delivery and children with clinical failure through 96 weeks. DRMs were identified using the Stanford HIV Drug Resistance Database.

resultsIn 27 infants, median PBMC HIV-1 proviral load was 492 copies/ml [IQR: 78-1246 copies/ml] at a median of 2 days (range 1-32); 18 (66.7%) had no DRMs detected; six (22.2%) had DRMs detected in defective DNA only, and three (11.1%) had DRMs in both defective and intact DNA (P = 0.09). A total of 60 of 151 (37.7%) defective sequences had at least one DRM: 31.8% NNRTI, 15.2% NRTI, 5.3% protease inhibitor, and 15.5% INSTI-associated mutations. In intact sequences, 33 of 106 (31.1%) had at least 1 DRM: 29.2% NNRTI, 7.5% NRTI, 0.9% protease inhibitor, and no INSTI-associated mutations. For all three infants with intact sequence DRMs, corresponding DRMs occurred in maternal plasma at delivery. Archived DRMs were detectable at a later clinical rebound on only one occasion.

conclusionDefective HIV-1 cell-associated DNA sequences may overestimate the prevalence of drug resistance among early-treated children. The impact of DRMs from intact proviruses on long-term treatment outcomes warrants further investigation.

Indexed as

Anti-HIV AgentsHIV InfectionsBotswanaDrug Resistance, ViralGenotypeHumansLeukocytes, MononuclearMutationAnti-HIV Agents

Identifiers

PMID34324451
PMCPMC8631156
OpenAlexW3186028821

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.