PMID- 32107887 OWN - NLM STAT- MEDLINE DCOM- 20201104 LR - 20240328 IS - 1758-2652 (Electronic) IS - 1758-2652 (Linking) VI - 23 IP - 2 DP - 2020 Feb TI - Rapid viral rebound after analytical treatment interruption in patients with very small HIV reservoir and minimal on-going viral transcription. PG - e25453 LID - 10.1002/jia2.25453 [doi] LID - e25453 AB - INTRODUCTION: Viral remission after analytical treatment interruption (ATI), termed post-treatment control, has been described in a small proportion of HIV-positive patients. This phenomenon has been separately associated to both low levels of HIV-1 proviral DNA as well as cell-associated RNA. We investigated whether the combination of both parameters could help predict delayed viral rebound after treatment interruption (TI). METHODS: We conducted an open single-arm ATI study in four Belgian HIV reference centres from January 2016 to July 2018. Eligible participants were adults who had fewer than 50 HIV-1 RNA copies/mL for more than two years, more than 500 CD4 cells/microL for more than three months, and were in general good health. Consenting participants who had fewer than 66 copies total HIV-1 DNA (t-DNA) and fewer than 10 copies cell-associated HIV-1 unspliced RNA (US-RNA) per million peripheral blood mononuclear cells (PBMCs), interrupted therapy and were monitored closely. Antiretroviral therapy (ART) was resumed after two consecutive viral loads exceeding 1000 copies or one exceeding 10,000 copies/mL. The primary outcome was the proportion of participants with fewer than 50 HIV-1 RNA copies/mL 48 weeks after TI. Secondary outcomes were time to viral rebound, the frequency of serious adverse events (AEs) and evolution of t-DNA and US-RNA after TI. RESULTS: All 16 consenting participants who interrupted therapy experienced rapid viral rebound two to eight weeks after TI. No serious AEs were observed. Levels of t-DNA and US-RNA increased after TI but returned to pre-ATI levels after treatment restart. None of the studied demographic, clinical and biological parameters were predictive of time of viral rebound. CONCLUSIONS: The combination of low levels of t-DNA and US-RNA in PBMCs, corresponding respectively to a small and transcriptionally silent viral reservoir, is not predictive of viral remission after TI in patients on ART. CI - (c) 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society. FAU - Pannus, Pieter AU - Pannus P AUID- ORCID: 0000-0001-9516-8305 AD - Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. AD - Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Rutsaert, Sofie AU - Rutsaert S AD - Department of General Internal Medicine, HIV Cure Research Centre, Ghent University Hospital and Ghent University, Ghent, Belgium. FAU - De Wit, Stephane AU - De Wit S AD - Saint Pierre University Hospital, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Allard, Sabine D AU - Allard SD AD - HIV Reference Centre, Universitair Ziekenhuis Brussel, Brussels, Belgium. FAU - Vanham, Guido AU - Vanham G AD - Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. AD - Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. FAU - Cole, Basiel AU - Cole B AD - Department of General Internal Medicine, HIV Cure Research Centre, Ghent University Hospital and Ghent University, Ghent, Belgium. FAU - Nescoi, Coca AU - Nescoi C AD - Saint Pierre University Hospital, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Aerts, Joeri AU - Aerts J AD - Vrije Universiteit Brussel, Brussels, Belgium. FAU - De Spiegelaere, Ward AU - De Spiegelaere W AD - Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium. FAU - Tsoumanis, Achilleas AU - Tsoumanis A AD - Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. FAU - Couttenye, Marie-Madeleine AU - Couttenye MM AD - Antwerp University Hospital, University of Antwerp, Antwerp, Belgium. FAU - Herssens, Natacha AU - Herssens N AD - Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. FAU - De Scheerder, Marie-Angelique AU - De Scheerder MA AUID- ORCID: 0000-0002-2929-9961 AD - Department of General Internal Medicine, HIV Cure Research Centre, Ghent University Hospital and Ghent University, Ghent, Belgium. FAU - Vandekerckhove, Linos AU - Vandekerckhove L AD - Department of General Internal Medicine, HIV Cure Research Centre, Ghent University Hospital and Ghent University, Ghent, Belgium. FAU - Florence, Eric AU - Florence E AD - Departments of Clinical and Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. LA - eng SI - ClinicalTrials.gov/NCT02590354 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - J Int AIDS Soc JT - Journal of the International AIDS Society JID - 101478566 RN - 0 (DNA, Viral) SB - IM MH - Adult MH - CD4-Positive T-Lymphocytes/virology MH - DNA, Viral MH - Female MH - HIV Infections/drug therapy/*virology MH - HIV-1/genetics/*physiology MH - Humans MH - Leukocytes, Mononuclear/virology MH - Male MH - Middle Aged MH - Remission Induction MH - Transcription, Genetic MH - Viral Load MH - Virus Replication PMC - PMC7046528 OTO - NOTNLM OT - HIV OT - cell-associated HIV RNA OT - post-treatment control OT - total HIV DNA OT - treatment interruption OT - viral reservoir EDAT- 2020/02/29 06:00 MHDA- 2020/11/05 06:00 PMCR- 2020/02/27 CRDT- 2020/02/29 06:00 PHST- 2019/09/10 00:00 [received] PHST- 2020/01/20 00:00 [accepted] PHST- 2020/02/29 06:00 [entrez] PHST- 2020/02/29 06:00 [pubmed] PHST- 2020/11/05 06:00 [medline] PHST- 2020/02/27 00:00 [pmc-release] AID - JIA225453 [pii] AID - 10.1002/jia2.25453 [doi] PST - ppublish SO - J Int AIDS Soc. 2020 Feb;23(2):e25453. doi: 10.1002/jia2.25453.