1. Plasma, intracellular and lymph node antiretroviral concentrations and HIV DNA change during primary HIV infection: Results from the INACTION P25 study.
- Author
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De Nicolò A, Palermiti A, Dispinseri S, Marchetti G, Trunfio M, De Vivo E, D'Avolio A, Muscatello A, Gori A, Rusconi S, Bruzzesi E, Gabrieli A, Bernasconi DP, Bandera A, Nozza S, and Calcagno A
- Subjects
- Humans, Male, Adult, Female, Anti-HIV Agents therapeutic use, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents blood, Oxazines, Middle Aged, RNA, Viral blood, Plasma chemistry, Plasma virology, Piperazines blood, Emtricitabine therapeutic use, Emtricitabine pharmacokinetics, Emtricitabine blood, Heterocyclic Compounds, 3-Ring pharmacokinetics, Heterocyclic Compounds, 3-Ring therapeutic use, Heterocyclic Compounds, 3-Ring blood, Pyridones therapeutic use, Darunavir therapeutic use, Darunavir pharmacokinetics, Darunavir blood, HIV-1 drug effects, Viral Load, Alanine blood, Anti-Retroviral Agents therapeutic use, Anti-Retroviral Agents pharmacokinetics, Anti-Retroviral Agents blood, HIV Infections drug therapy, HIV Infections virology, DNA, Viral blood, Leukocytes, Mononuclear virology, Lymph Nodes virology, Tenofovir therapeutic use, Tenofovir pharmacokinetics, Tenofovir blood
- Abstract
Despite its effectiveness, combination antiretroviral treatment (cART) has a limited effect on HIV DNA reservoir, which establishes early during primary HIV infection (PHI) and is maintained by latency, homeostatic T-cells proliferation, and residual replication. This limited effect can be associated with low drug exposure in lymphoid tissues and/or suboptimal adherence to antiretroviral drugs (ARVs). The aim of this study was to assess ARV concentrations in plasma, peripheral blood mononuclear cells (PBMCs) and lymph nodes (LNs), and their association to HIV RNA and HIV DNA decay during PHI. Participants were randomised to receive standard doses of darunavir/cobicistat (Arm I), dolutegravir (Arm II) or both (Arm III), with a backbone of tenofovir alafenamide and emtricitabine. Total HIV DNA was measured using digital-droplet PCR in PBMCs at baseline, 12 and 48 weeks. Drug concentrations in plasma and PBMCs were determined at 2, 12 and 48 weeks (LNs at 12 weeks) by UHPLC-MS/MS. Seventy-two participants were enrolled, mostly male (n=68), with a median age of 34 years and variable Fiebig stages (V-VI 57.7%, I-II 23.9%, and III-IV 18.3%). Twenty-six patients were assigned to Arm I, 27 to Arm II and 19 to Arm III. After 48 weeks, most patients had undetectable viremia, with minor differences in HIV RNA decay between arms. Patients with Fiebig I-II showed faster HIV RNA and HIV DNA decay. Intracellular tissue penetration was high for nucleoside analogues and low-moderate for darunavir and dolutegravir. Only tenofovir diphosphate concentrations in PBMCs showed correlation with HIV DNA decay. Overall, these results indicate that the timing of treatment initiation and intracellular tenofovir penetration are primary and secondary factors, respectively, affecting HIV reservoir., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2024
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