Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day ⁻¹ in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml ⁻¹ ; interquartile range [IQR], 0.60 to 1.50 ng ml ⁻¹ ) and tenofovir (TFV; median, 15.0 ng ml ⁻¹ ; IQR, 8.8 to 23.3 ng ml ⁻¹ ), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10 ⁶ cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations.

Carbon dioxide is an appealing renewable feedstock for industrial chemical processes. This does not mean, however, that all chemical processes using CO₂ are environmentally-friendly. Perspectives on the sustainability of CO₂ utilization and artificial photosynthesis are provided. The discussions focus on the photocatalytic production of C_x (x ≥ 2) compounds, where all the carbon in the products is derived from CO₂ . This area of research, while promising, has received far less attention than analogous systems leading to C₁ products.

Systematic variation of the ligand environment has allowed design of the absorbance characteristics of polypyridyl complexes of ruthenium(II) to produce “black absorbers” which absorb throughout the visible region. The presence of acceptor ligands with low-lying π* levels red shift the energies of the lowest energy MLCT bands, while MLCT and π → π* bands originating on other ligands can be used to fill in the higher-energy regions of the spectrum. Incorporation of anionic ligands or other electron-donating ligands causes a red shift in MLCT band energies compared to bpy by manipulation of dπ energy levels. Attention to these design principles has led to the synthesis of complexes which absorb appreciably in the near IR, and are free from complications caused by thermally accessible dd states. Although their emission energies (and energy gaps) are at low energy in the near IR, the use of lowest lying, delocalised acceptor ligands provides lifetime enhancements (compared to bpy) that can be dramatic.