No single-tablet antiretroviral (ARV) regimens (STRs) are approved for patients with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) on hemodialysis (HD). Based on known pharmacokinetic (PK) properties, abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) STR may represent a promising option. This case series presents the safety and efficacy of ABC/3TC/DTG STR in patients with HIV and ESRD on HD. Patients were included if they were HIV-positive, maintained on intermittent HD for ESRD, switched to an ARV regimen containing ABC/3TC/DTG, and had at least one set of virologic data before and after the switch. Average age (±standard deviation) was 59 (±8) years. The majority of patients were cis-gender male and non-Hispanic Black. Only one demonstrated clinically significant resistance at baseline. All were on multiple-tablet regimens prior to the switch. Five patients (83%) achieved undetectable HIV-RNA after the switch while only four patients (46%) were undetectable immediately prior. No decline in immune function was noted. ABC/3TC/DTG STR was well tolerated. Only one patient self-reported an adverse event (nausea), which resolved without drug discontinuation. Based on these data, it appears that ABC/3TC/DTG may be a safe and effective ARV-STR option for patients with HIV and ESRD on HD. A larger trial including a PK analysis is needed to confirm these findings.

γ-Lactamases are versatile enzymes used for enzymatic kinetic resolution of racemic Vince lactam (2-azabicyclo[2.2.1]hept-5-en-3-one) in the industry. Optically pure enantiomers and their hydrolytic products are widely employed as key chemical intermediates for developing a wide range of carbocyclic nucleoside medicines, including US FDA-approved drugs peramivir and abacavir. Owing to the broad applications in the healthcare industry, the resolution process of Vince lactam has witnessed tremendous progress during the past decades. Some of the most important advances are the enzymatic strategies involving γ-lactamases. The strong industrial demand drives the progress in various strategies for discovering novel biocatalysts. In the past few years, several new scientific breakthroughs, including the genome-mining strategy and elucidation of several crystal structures, boosted the research on γ-lactamases. So far, several families of γ-lactamases for resolution of Vince lactam have been discovered, and their number is continuously increasing. The purpose of this mini-review is to describe the discovery strategy and classification of these intriguing enzymes and to cover our current knowledge on their potential biological functions. Moreover, structural properties are described in addition to their possible catalytic mechanisms. Additionally, recent advances in the newest approaches, such as immobilization to increase stability, and other engineering efforts are introduced.

The implementation of a de novo personalized medicine program in a rural community health system serving an underserved population is described. Focusing on the safe use of drugs impacted by genetic variations in the non-oncology setting, we first addressed drug-gene pairs designated by the US FDA in black-box warnings (codeine, clopidogrel, abacavir, carbamazepine). The program's first success was a policy change to remove codeine from the pediatric formulary, rather than a testing recommendation. Pilot studies were then conducted with primary care providers to get them familiar with pharmacogenetic testing, and a consultative outpatient clinic for patients was developed. The assessment, planning, implementation, challenges, successes and lessons learned are described.

Combination abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) is approved as a first-line treatment for antiretroviral naïve patients. This report investigated the immunovirological outcome and total HIV-1 DNA decay in a small cohort of naïve HIV-1-positive patients treated with this regimen. In the presence of viral suppression and increased lymphocyte T CD4+ cells, the quantitative analysis of total HIV-1 DNA content revealed a significant decay after 12 months of treatment. Subsequently, we deintensificated the treatment of these patients from (ABC/3TC/DTG) to lamivudine plus dolutegravir (3TC/DTG) after 12 months of virological suppression, as a strategy of "induction-maintenance" therapy. The analysis of HIV-1 RNA viral load, total HIV-1 DNA, CD4+ T lymphocyte count and CD8+ HLA-DR+ T lymphocyte percentage after a mean 3.5 months of therapy deintensification showed no significant difference with respect to data detected after 12 months of ABC/3TC/DTG treatment in the presence of continuous viral suppression. These results indicate that the deintensification of highly active antiretroviral therapy (HAART) from ABC/3TC/DTG to 3TC/DTG effectively controls HIV-1 replication and in the early period does not induce any significant variations of total HIV-1 DNA. This suggests that HAART deintensification might be proposed as a therapeutic evolution in the treatment of HIV-1 infection.

(-)-γ-Lactam ((-)-2-azabicyclo[2.2.1]hept-5-en-3-one) has attracted increasing attention as the chiral intermediate of carbocyclic nucleosides most of which serve as pharmaceutical agents such as anti-HIV/HBV drugs abacavir and carbovir. So far, developing in vitro (+)-γ-lactamase-mediated biotransformation has been one of the most efficient approaches for the production of (-)-γ-lactam. In this study, the catalytic activity of the (+)-γ-lactamase from Sulfolobus solfataricus P2 was engineered by semi-rational design. Molecular docking and molecular dynamics simulation were carried out to target the key positions relevant to catalytic activity. Nine amino acid residues were selected for site saturation mutagenesis. To expedite the screening process, a sensitive colorimetric high-throughput screening method was established based on the Rimini test which was originally applied to distinguish primary amines from secondary amines. The screening process resulted in the achievement of several efficient mutants: V203N, V203Q, I336H, I336R, and Y388H. Synergy effects led to four final mutants (V203N/I336R, V203N/Y388H, I336R/Y388H, and V203N/I336R/Y388H) with enhanced enzyme activity after the combination of positive single mutants. The best mutant V203N/Y388H/I336R displayed a 21-fold higher enzyme efficiency (kcat/KM) compared to the wild-type enzyme. The result demonstrated that the biotransformation using the triple mutant as the catalyst reached > 49% conversion and > 99% enantiomeric excess at 80 °C after 2 h, which made it a good catalyst candidate to produce (-)-γ-lactam. The possible mechanism responsible for the improvement in the catalytic activity was explicated by analyzing the protein-ligand binding modes and interaction between the protein and the ligand.