Tenofovir disoproxil fumarate tdf

To select patients for antiviral therapy, the EASL treatment criteria were applied.²² (link) In the absence of contraindications, tenofovir disoproxil fumarate (TDF; Gilead Sciences, Foster City, USA), one 300-mg pill per day, was provided free of charge. Adherence to treatment was assessed by clinicians every 3 months using the Morisky scale.²³ (link)

Infected mice with detectable viremia were treated orally for two weeks with cART composed of drugs that block new infections. The cART regimen consisting of Truvada^® [tenofovir disoproxil fumarate (TDF; 300 mg/tablet), emtricitabine (FTC; 200 mg/tablet) (Gilead Sciences)] and Isentress® [raltegravir (RAL; 400 mg/tablet) (Merck)], scaled down to the equivalent mouse dosage using the appropriate conversion factor, was administered in a drinking water formulation (sweetened water gel, Medidrop® Sucralose, ClearH₂0). For 200 ml Medidrop^®, ½ Truvada tablet, and ½ Isentress tablet were crushed to powder, mixed by vigorous shaking, and changed weekly as per doses calculated previously⁶⁴ . Mice were bled by retro-orbital bleeding, and peripheral blood cell populations and plasma viral loads were analyzed periodically using RT-qPCR. The oral cART regimen was withdrawn after two weeks and exosome treatment was initiated. Exosomes derived from HEK293T cells packed with nLuc, ZFP, or ZPAMt were retro-orbitally injected at a concentration of 100 × 10⁹ in 100 ul sterile PBS once a week for 6 weeks.

Six Indian-origin, SPF RMs (M. mulatta) were sourced from the YNPRC colony and single-housed at YNPRC in an animal BSL-2 facility as previously described (7 (link)). All RMs were male, between 43 and 46 months old at time of infection, and were Mamu-B*08^– and -B*17^– with 2 being Mamu-A*01⁺ (Supplemental Table 6). RMs were infected i.v. with 300 TCID₅₀ SIVmac₂₃₉ and at d35 p.i. began a 3-drug, daily ART regimen consisting of an integrase inhibitor (2.5 mg/kg dolutegravir/DTG; ViiV Healthcare) and 2 nucleoside reverse transcriptase inhibitors (40 mg/kg emtricitabine/FTC and 5.1 mg/kg tenofovir disoproxil fumarate/TDF; Gilead Sciences) coformulated in 15% kleptose (Roquette America) for subcutaneous administration (63 (link)). The anti–IL-10 mAb (see Formulation of the anti–IL-10 mAb) was delivered i.v. without pretreatment at d211 p.i. at 10 mg/kg and again 27 days later (d238 p.i.) at 20 mg/kg. Notably, RBf16 only received 14.45 mg/kg at the second anti–IL-10 mAb administration because of limited compound yields. Necropsy was performed on all RMs at d263 p.i. with tissues, including LN biopsies, collected postmortem. A schematic of the study design, generated with BioRender (biorender.com), is given in Figure 5A.