Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen.
| العنوان: | Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen. |
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| المؤلفون: | Ferreira RC; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada., Reynolds SJ; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.; Rakai Health Sciences Program, Kalisizo, Uganda., Capoferri AA; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Baker O; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Brown EE; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Klock E; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Miller J; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Lai J; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Saraf S; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Kirby C; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Lynch B; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Hackman J; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Gowanlock SN; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario., Tomusange S; Rakai Health Sciences Program, Kalisizo, Uganda., Jamiru S; Rakai Health Sciences Program, Kalisizo, Uganda., Anok A; Rakai Health Sciences Program, Kalisizo, Uganda., Kityamuweesi T; Rakai Health Sciences Program, Kalisizo, Uganda., Buule P; Rakai Health Sciences Program, Kalisizo, Uganda., Bruno D; Genomic Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT., Martens C; Genomic Unit, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT., Rose R; BioInfoExperts, LLC, Thibodaux, LA., Lamers SL; BioInfoExperts, LLC, Thibodaux, LA., Galiwango RM; Rakai Health Sciences Program, Kalisizo, Uganda., Poon AFY; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario., Quinn TC; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD., Prodger JL; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario.; Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario., Redd AD; Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. |
| المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2023 May 16. Date of Electronic Publication: 2023 May 16. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | The principal barrier to an HIV cure is the presence of a latent viral reservoir (LVR) made up primarily of latently infected resting CD4+ (rCD4) T-cells. Studies in the United States have shown that the LVR decays slowly (half-life=3.8 years), but this rate in African populations has been understudied. This study examined longitudinal changes in the inducible replication competent LVR (RC-LVR) of ART-suppressed Ugandans living with HIV (n=88) from 2015-2020 using the quantitative viral outgrowth assay, which measures infectious units per million (IUPM) rCD4 T-cells. In addition, outgrowth viruses were examined with site-directed next-generation sequencing to assess for possible ongoing viral evolution. During the study period (2018-19), Uganda instituted a nationwide rollout of first-line ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen that consisted of one NNRTI and the same two NRTI. Changes in the RC-LVR were analyzed using two versions of a novel Bayesian model that estimated the decay rate over time on ART as a single, linear rate (model A) or allowing for an inflection at time of DTG initiation (model B). Model A estimated the population-level slope of RC-LVR change as a non-significant positive increase. This positive slope was due to a temporary increase in the RC-LVR that occurred 0-12 months post-DTG initiation (p<0.0001). This was confirmed with model B, which estimated a significant decay pre-DTG initiation with a half-life of 7.7 years, but a significant positive slope post-DTG initiation leading to a transient estimated doubling-time of 8.1 years. There was no evidence of viral failure in the cohort, or consistent evolution in the outgrowth sequences associated with DTG initiation. These data suggest that either the initiation of DTG, or cessation of NNRTI use, is associated with a significant temporary increase in the circulating RC-LVR. |
| التعليقات: | Update in: EBioMedicine. 2024 Mar 4;:105040. (PMID: 38485563) |
| معلومات مُعتمدة: | UM1 AI164565 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20230609 Latest Revision: 20240412 |
| رمز التحديث: | 20240413 |
| مُعرف محوري في PubMed: | PMC10246077 |
| DOI: | 10.1101/2023.05.12.23289896 |
| PMID: | 37292785 |
| قاعدة البيانات: | MEDLINE |
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