Humans ; Tenofovir/therapeutic use* ; Emtricitabine/therapeutic use* ; HIV Infections/drug therapy* ; Anti-HIV Agents/therapeutic use*

BACKGROUND: Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-naïve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-naïve PWH in China. METHODS: This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs . ≥100,000 copies/mL) and CD4 + cell count (<200 vs . ≥200 cell/µL). Median time to TND VL was assessed by Kaplan-Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). RESULTS: We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. CONCLUSIONS In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.
Adult ; Humans ; Anti-HIV Agents/therapeutic use* ; China ; Emtricitabine/pharmacology* ; HIV Infections/drug therapy* ; HIV-1 ; Lamivudine/pharmacology* ; Lipids ; Retrospective Studies

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*

Adenine/analogs & derivatives* ; Anti-HIV Agents/therapeutic use* ; Cobicistat/therapeutic use* ; Drug Combinations ; Emtricitabine/therapeutic use* ; HIV ; HIV Infections/drug therapy* ; Humans ; Postoperative Complications ; Quinolones ; Viral Load

Although surgery is the mainstay of local treatment for skin cancer, definitive radiation therapy (RT) has been also applied for patients who are unable to tolerate surgery. Definitive RT regimens usually consist of daily treatment for 4–7 weeks. Such protracted daily RT regimens, however, would not be feasible for non-compliant patients or patients who are unable to make multiple daily trips for weeks. Without treatment, however, skin cancers can continuously progress and cause distressing symptoms. A cyclical hypofractionated RT (QUAD Shot: 14 Gy in 4 fractions, twice-daily treatments with 6 hours interval on 2 consecutive days) can be a practical RT regimen for those patients. In this report, we present the successful treatment course of repeated QUAD Shots in a 79-year-old patient with neglected skin cancer that was disfiguring his face yet declined definitive surgery and protracted RT. We also evaluated and compared biologically equivalent doses between QUAD Shots and conventionally fractionated protracted RT regimens.
Aged ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Humans ; Skin Neoplasms ; Skin

Pioglitazone is known to have antidiabetic effects through decreasing peripheral, hepatic and vascular insulin resistance by the stimulation of PPAR gamma. To address the possible genetic factors affecting the pharmacokinetics (PK) of pioglitazone, 27 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 15 mg pioglitazone and reference drug PK parameters were used. We used Illumina Human610 Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters. We found 35 significant SNPs (P < 0.0001) in C(max), 1,118 significant SNPs (P < 0.0001) in T(max) and 1,259 significant SNPs (P < 0.0001) in AUC(inf) from whole genome analysis. For clinical pharmacological purpose, we selected SNPs from several phase I and II drug metabolizing enzyme and analyzed PK parameters with genotypes. Four SNPs (rs7761731 and rs3799872 from CYP39A1; rs156697 from GSTO2; rs1558139 from CYP4F2) showed significant associations with pioglitazone C(max). In the T(max) group, seven SNPs from 3 genes (rs3766198 from CYP4B1; rs2270422 from GSTZ1; rs2054675, rs10500282, rs3745274, rs8192719, and rs11673270 from CYP2B6) had significant associations. In the AUC(inf) group, seven SNPs from 4 genes (rs11572204 from CYP2J2; rs4148280 from UGT2A1, rs4646422 from CYP1A1; rs3745274, rs8192719, rs11673270, and rs707265 from CYP2B6) showed significant associations with pioglitazone absorption. These results showed that genetic makeup could affect the PK parameters and these informations could be provide information for personalized pioglitazone therapy.
Absorption ; Cytochrome P-450 CYP1A1 ; DNA ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Genome ; Genotype ; Humans ; Insulin Resistance ; Linear Models ; Male ; Mass Screening* ; Pharmacogenetics ; Pharmacokinetics* ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; PPAR gamma ; Therapeutic Equivalency ; Volunteers

BACKGROUND: The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. RESULTS: A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. CONCLUSION: Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.
Anti-Retroviral Agents ; Antiretroviral Therapy, Highly Active* ; Atazanavir Sulfate ; Creatinine* ; Darunavir ; Emtricitabine ; Follow-Up Studies ; HIV ; Humans ; Incidence* ; Integrases ; Lopinavir ; Medical Records ; Protease Inhibitors ; Retrospective Studies ; RNA-Directed DNA Polymerase ; Tenofovir

OBJECTIVE: To analyze the fatigue resistance, debonding force, and failure type of fiber-reinforced composite, polyethylene ribbon-reinforced, and braided stainless steel wire lingual retainers in vitro. METHODS: Roots of human mandibular central incisors were covered with silicone, mimicking the periodontal ligament, and embedded in polymethylmethacrylate. The specimens (N = 50), with two teeth each, were randomly divided into five groups (n = 10/group) according to the retainer materials: (1) Interlig (E-glass), (2) everStick Ortho (E-glass), (3) DentaPreg Splint (S2-glass), (4) Ribbond (polyethylene), and (5) Quad Cat wire (stainless steel). After the recommended adhesive procedures, the retainers were bonded to the teeth by using flowable composite resin (Tetric Flow). The teeth were subjected to 10,00,000 cyclic loads (8 Hz, 3 - 100 N, 45degrees angle, under 37 +/- 3degrees C water) at their incisoproximal contact, and debonding forces were measured with a universal testing machine (1 mm/min crosshead speed). Failure sites were examined under a stereomicroscope (x40 magnification). Data were analyzed by one-way analysis of variance. RESULTS: All the specimens survived the cyclic loading. Their mean debonding forces were not significantly different (p > 0.05). The DentaPreg Splint group (80%) showed the highest incidence of complete adhesive debonding, followed by the Interlig group (60%). The everStick Ortho group (80%) presented predominantly partial adhesive debonding. The Quad Cat wire group (50%) presented overlying composite detachment. CONCLUSIONS: Cyclic loading did not cause debonding. The retainers presented similar debonding forces but different failure types. Braided stainless steel wire retainers presented the most repairable failure type.
Adenine ; Adhesives ; Animals ; Carbamates ; Cats ; Collodion ; Composite Resins ; Deoxycytidine ; Drug Combinations ; Fatigue ; Humans ; Incidence ; Incisor ; Organophosphonates ; Periodontal Ligament ; Polyethylene ; Polyethylenes ; Polymethyl Methacrylate ; Quinolones ; Recurrence ; Retention (Psychology) ; Silicones ; Splints ; Stainless Steel ; Thiazoles ; Tooth ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

OBJECTIVES: The objective of this paper is to assess which wide type monitor configurations are preferred when physicians use an Electronic Medical Record (EMR) system in an outpatient clinic setting. METHODS: We selected three kinds of monitor configurations available for adoption at outpatient clinics with reference to monitor market trends. Fifteen attending physicians of the Seoul National University Bundang Hospital used each monitor configuration in their outpatient clinics. After completing the outpatient sessions, they selected the best monitor configuration for criteria described in five questionnaire items. We counted the number of votes and reviewed opinions of participants. RESULTS: The Wide Quad High Definition (WQHD) 27-inch single monitor configuration was most preferred for all questionnaire items. All participants answered that the WQHD 27-inch single monitor configuration was the best for desk space utilization. Eleven out of fifteen participants chose the WQHD 27-inch single monitor configuration as the most suitable monitor for outpatient practice. CONCLUSIONS: This study found that physicians preferred the WQHD 27-inch single monitor configuration in outpatient clinic settings. Healthcare organizations need to consider this finding when they purchase wide type monitors for EMR systems instead of the standard type monitor.
Adenine ; Adoption ; Ambulatory Care Facilities ; Carbamates ; Computer Terminals ; Delivery of Health Care ; Deoxycytidine ; Drug Combinations ; Electronic Health Records ; Electronics ; Electrons ; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ; Humans ; Organophosphonates ; Organothiophosphorus Compounds ; Outpatients ; Personal Satisfaction ; Quinolones ; Thiazoles ; User-Computer Interface ; Surveys and Questionnaires