Distribution and reduction magnitude of HIV-DNA burden in CD4+ T cell subsets depend on art initiation timing
| Autor: | Patricia Fischer, Béatrice Uring-Lambert, Geneviève Beck-Wirth, Jean-Pierre Faller, Mahsa Mosheni-Zadeh, Anne Fuchs, David Rey, Christine Cheneau, Cindy Barnig, Marie-Laure Batard, Guinevere Q. Lee, Marialuisa Partisani, Samira Fafi-Kremer, Martin Martinot, Siamak Bahram, Pierre Gantner |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male medicine.medical_specialty Time Factors Anti-HIV Agents Pyridones Art initiation 030106 microbiology Immunology Patient subgroups HIV Infections Real-Time Polymerase Chain Reaction Gastroenterology Piperazines 03 medical and health sciences chemistry.chemical_compound Young Adult T-Lymphocyte Subsets Internal medicine Antiretroviral Therapy Highly Active Oxazines medicine Immunology and Allergy Distribution (pharmacology) Humans Longitudinal Studies Prospective Studies Aged Cd4 t cell business.industry Middle Aged Antiretroviral therapy Virological failure Regimen 030104 developmental biology Infectious Diseases chemistry Dolutegravir DNA Viral Female business Heterocyclic Compounds 3-Ring Follow-Up Studies |
| Zdroj: | AIDS (London, England). 32(7) |
| ISSN: | 1473-5571 |
| Popis: | OBJECTIVE The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4 T-cell subsets in individuals starting successful dolutegravir-based regimens. DESIGN Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997). METHODS CD4 T-cells from baseline and week 48 of successful treatment were sorted into effector memory (TEM), transitional memory (TTM), central memory (TCM) and naive (TN) cell groups for total HIV-DNA measurements by qPCR. Bayesian methods were used to estimate the posterior probability of a HIV-DNA decrease more than 0.25 log copies/10 cells at week 48. RESULTS All patients achieved HIV-RNA suppression at 48 weeks. At baseline and week 48, the highest contributions to the HIV-DNA-infected pool from CD4 T cells were observed in TTM cells in the AI group (62.4 and 60.2%, respectively), but in TCM cells for the CI, VS and VF groups (54.6 and 59.4%, 58.2 and 62.9%, 62.4 and 67.2%), respectively. HIV-DNA burden declined in all subsets after 48 weeks of treatment in the AI (probability (Pr) > 91%), CI (Pr > 52%) and VF (Pr > 52%) groups, but only in TEM cells in the VS group (Pr = 95%). CONCLUSION Our study showed that dolutegravir-based treatment reduced the HIV-DNA cellular burden in individuals from the AI, CI and VF groups, though the reduction levels differed between the patient subgroups. Early treated patients had the highest probability of HIV-DNA reduction. Interestingly, in the aviremic VS group, HIV-DNA reduction was limited to TEM cells. |
| Databáze: | OpenAIRE |
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