Evidence map›Paper›PMID 39155436›Full record

SynthesisJournal of the International AIDS Society2024

The impact of analytical treatment interruptions and trial interventions on time to viral re-suppression in people living with HIV restarting ART in cure-related clinical studies: a systematic review and meta-analysis.

Ming Jie Lee, Miles Eason, Antonella Castagna, Galli Laura, Marie-Angelique De Scheerder, James Riley, Pablo Tebas, Jesper Gunst, Ole Søgaard, Eric Florence and 5 more

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Journal of the International AIDS Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Trial
  2. Article
  3. Observational
  4. Review
  5. Article
  6. Observational
  7. Article
  8. Article
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.

Ming Jie Lee *Department of Infectious Disease, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-5244-0070
Miles Eason *Faculty of Medicine, Imperial College London, London, UK.
Antonella CastagnaClinic of Infectious Diseases, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
Galli LauraInfectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Marie-Angelique De ScheerderDepartment of General Internal Medicine, Ghent University Hospital, Gent, Belgium.
James RileyCenter for Cellular Immunotherapies, Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Pablo TebasCenter for Cellular Immunotherapies, Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jesper GunstDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.ORCID https://orcid.org/0000-0002-3787-0259
Ole SøgaardDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Eric FlorenceDepartments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Eugene KroonSEARCH Research Foundation, Bangkok, Thailand.
Mark De SouzaSEARCH Research Foundation, Bangkok, Thailand.
Beatriz MotheIrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain.
Marina CaskeyLaboratory of Molecular Immunology, The Rockefeller University, New York, New York, USA.
Sarah FidlerDepartment of Infectious Disease, Imperial College London, London, UK.ORCID https://orcid.org/0000-0003-1676-7583

Funding

BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination ImmunotherapyUM1AI164570 · NIAID · WISTAR INSTITUTE · PI Luis J Montaner, James L. Riley · 2021 to 2026
$34.7M
University of Pennsylvania HIV Clinical Trials UnitUM1AI069534 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ian Frank, PABLO TEBAS · 2012 to 2026
$33.0M
NIAID NIH HHS UM1 AI069534NIAID NIH HHS UM1 AI164570UK Medical Research Council MR/W024454/1
6 · The paper itself

Abstract

introductionTo assess the effectiveness of novel HIV curative strategies, "cure" trials require periods of closely monitored antiretroviral therapy (ART) analytical treatment interruptions (ATIs). We performed a systematic review and meta-analysis to identify the impact of ATI with or without novel therapeutics in cure-related studies on the time to viral re-suppression following ART restart.

methodsMedline, Embase and Web of Science databases were searched for human studies involving ATIs from 1 January 2015 till 22 April 2024. The primary outcome was time to first viral re-suppression (plasma HIV viral load [VL] <50 copies/ml) stratified by receipt of interventional drug with ATI (IA) or ATI-only groups. Random-effects proportional meta-analysis and multivariable Cox proportional hazards analysis were performed using R.

resultsOf 1073 studies screened, 13 were included that met the inclusion criteria with VL data available after restarting ART (n = 213 participants). There was no difference between time to viral suppression in IA or ATI-only cohorts (p = 0.22). For 87% of participants, viral suppression within 12 weeks of ART restart was achieved, and all eventually had at least one VL <50 copies/ml during follow-up. After adjusting for covariables, while participants in the IA cohort were associated with less rapid suppression (adjusted hazard ratio [aHR] 0.61, 95% CI 0.40-0.94, p = 0.026), other factors include greater log VL at ART restart (aHR 0.56, 95% CI 0.46-0.68, p<0.001), duration since HIV diagnosis (aHR 0.93, 95% CI 0.89-0.96) and longer intervals between HIV VL monitoring (aHR 0.66, 95% CI 0.59-0.74, p<0.001). However, the use of integrase inhibitors was associated with more rapid viral suppression (aHR 1.74, 95% CI 1.16-2.59). DISCUSSION: When designing studies involving ATIs, information on time to viral re-suppression after restarting ART is important to share with participants, and should be regularly monitored and reported, to assess the impact and safety of specific trial interventions in ATI studies.

conclusionsThe majority of participants achieved viral suppression after restarting ART in ATI studies. ART regimens containing integrase inhibitors and frequent VL monitoring should be offered for people restarting ART after ATI studies to ensure rapid re-suppression.

Indexed as

Anti-HIV AgentsHIV InfectionsViral LoadHumansTime FactorsTreatment OutcomeWithholding TreatmentAnti-HIV Agentsantiretroviral therapyATIHIVHIV curetreatment interruptionviral suppression

Identifiers

PMID39155436
PMCPMC11330850

What OpenQuestion holds

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Registered trials

None linked

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.