Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial.

Tytuł:: Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial.
Autorzy:: Payne H; Institute of Child Health, University College London, London, United Kingdom. .; Department of Paediatrics and Child Health, Family Center for Research With Ubuntu, Stellenbosch University, Cape Town, South Africa. .; Department of Paediatric Infectious Diseases, Imperial College London, Room 235, Medical School Building, Norfolk Place, London, W21PG, United Kingdom. .
Chan MK; MRC Clinical Trials Unit at University College London, London, United Kingdom.
Watters SA; Department of Infection and Immunity, University College London, London, United Kingdom.; Department of Clinical Microbiology and Virology, University College London Hospitals NHS Trust, London, United Kingdom.
Otwombe K; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Hsiao NY; Division of Medical Virology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.
Babiker A; MRC Clinical Trials Unit at University College London, London, United Kingdom.
Violari A; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Cotton MF; Department of Paediatrics and Child Health, Family Center for Research With Ubuntu, Stellenbosch University, Cape Town, South Africa.
Gibb DM; MRC Clinical Trials Unit at University College London, London, United Kingdom.
Klein NJ; Institute of Child Health, University College London, London, United Kingdom.
Źródło:: AIDS research and therapy [AIDS Res Ther] 2021 Sep 29; Vol. 18 (1), pp. 63. Date of Electronic Publication: 2021 Sep 29.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : BioMed Central, 2004-
MeSH Terms:: HIV Infections*/drug therapy
HIV-1*/genetics
Child ; DNA, Viral/genetics ; Humans ; Leukocytes, Mononuclear ; Viral Load ; Virus Latency
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Grant Information:: MC_UU_00004/03 United Kingdom MRC_ Medical Research Council; 095182/Z/10/Z United Kingdom WT_ Wellcome Trust
Contributed Indexing:: Keywords: ART; CHER; Children; HIV-1 proviral DNA; Reservoir
Substance Nomenclature:: 0 (DNA, Viral)
Entry Date(s):: Date Created: 20210930 Date Completed: 20211013 Latest Revision: 20220317
Update Code:: 20240105
PubMed Central ID:: PMC8482761
DOI:: 10.1186/s12981-021-00389-1
PMID:: 34587974
: Czasopismo naukowe

Pełny tekst

Background: Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial.
Methods: Infants with HIV < 12 weeks old with CD4% ≥ 25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4% < 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥ 24 weeks ART and two consecutive undetectable HIV-1 RNA 12-24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression.
Findings: Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p = 0.0003) and 248 weeks (p = 0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p = 0.0225) and 248 weeks (p = 0.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p = 0.0042).
Intepretation: Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of "immune-attenuation" through early HIV-1 exposure.
Funding: Wellcome Trust, National Institutes of Health, Medical Research Council.
(© 2021. The Author(s).)

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