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International Journal of Antimicrobial... May 2024To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes.
OBJECTIVE
To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes.
METHODS
Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analyzed using the Stanford University HIV Drug Resistance Database.
RESULTS
Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with ART duration of ≥3 years who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, p<0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new generation NNRTIs in patients with CRF08_BC; doravirine (r=1.0), rilpivirine (r=0.93), and etravirine (r=0.86) resistance highly correlated with efavirenz/nevirapine.
CONCLUSIONS
The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.
PubMed: 38795930
DOI: 10.1016/j.ijantimicag.2024.107215 -
Chemosphere May 2024This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces...
This study focuses on the removal and risk assessment of twenty emerging contaminants (ECs) and heavy metals in a REMIX water treatment plant (RWTP) that produces drinking water from combination of wastewater reuse and desalination. The membrane biological reactor (MBR) exhibit removal rates exceeding 95% of pharmaceuticals like acetaminophen, trimethoprim, diclofenac, naproxen, and emtricitabine. The efficiency of brackish reverse osmosis (BWRO) in removing ECs is highlighted, showing substantial efficacy with reduction rates of 99.5%, 75.5%, and 51.2% for sulfamethoxazole, venlafaxine, and benzotriazole, respectively. The advanced oxidation process based on Fenton process reveals removal (>95%) of emtricitabine, efavirenz, and carbamazepine. The study confirms that the combination of treatment units within the RWTP effectively removes heavy metals (>90%), complying with acceptable limits. Risk quotient (RQ) calculations indicate the efficiency of the RWTP in EC removal, serving as benchmarks for public acceptance of reclaimed water. In the context of heavy metals, the study concludes negligible cancer risks associated with reclaimed water consumption over a lifetime. Quantitative structure-activity relationship and occurrence, persistence, bioaccumulation and toxicity (OPBT) models were used to assess EC risk. The study screened and identified potential persistant, bio accumulating and toxic PBT ECs. Critical control points (CCPs) in the RWTP are identified, with brackish and seawater reverse osmosis (BWRO and SWRO) and advanced oxidation process (AOP) recognized as pivotal in hazard management. The study provides valuable insights on the removal of ECs and heavy metals in a wastewater reuse process and demonstrates potential of adopted process configuration in supplying safe drinking water from wastewater recycling.
PubMed: 38777194
DOI: 10.1016/j.chemosphere.2024.142396 -
Journal of Environmental Management May 2024In this work, exfoliated graphite was used to adsorb antiretroviral drugs from river water and wastewater. The exfoliated graphite was prepared from natural graphite by...
In this work, exfoliated graphite was used to adsorb antiretroviral drugs from river water and wastewater. The exfoliated graphite was prepared from natural graphite by intercalating it with the acids and exfoliating it at 800 °C. It was characterized using Fourier Transform Infrared Spectroscopy which showed phenolic, alcoholic, and carboxylic functional groups between 1000 cm-1 and 1700 cm-1. Energy-dispersive X-ray spectroscopy results showed carbon as the main element with splashes of oxygen. The Scanning Electron Microscopy images showed increased c-axis distance between graphene layers after intercalation, which further increased after the exfoliation. The exfoliation resulted in elongated distorted cylinders, which were confirmed by the lower density (0.0068 g/mL) of exfoliated graphite material compared to the natural graphite (0.54 g/mL). The X-ray diffraction pattern showed the characteristics of hexagonal phase graphitic structure by the diffraction plane (002) at 26.74°. Raman spectroscopy results showed the natural graphite, graphite intercalated, and exfoliated graphite contained the D, G, D', and G' peaks at about 1350 cm-1, 1570 cm-1, 2440 cm-1, and 2720 cm-1, respectively indicating that the material's crystallinity was not affected by the modification. The highest antiretroviral drugs removal (95-99%), from the water was achieved with a solution pH of 7, an adsorbent mass of 30 mg, and an adsorption time of 30 min. The kinetic model and adsorption isotherm studies showed that the experimental data fit well in pseudo-second-order kinetics and is well explained by Freundlich's adsorption isotherm. The maximum adsorption capacity of the exfoliated graphite for antiretroviral drugs ranges between 1.660 and 197.0, 1.660-232.5, and 1.650-237.7 mg/g for abacavir, nevirapine, and efavirenz, respectively. The obtained removal percentages were 100% in river water, 63-100% in influent and 70-100% in effluent wastewater unspiked samples.
PubMed: 38772233
DOI: 10.1016/j.jenvman.2024.121200 -
HIV/AIDS (Auckland, N.Z.) 2024Currently, Dolutegravir (DTG)-based regimens are administered to women on Option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect...
BACKGROUND
Currently, Dolutegravir (DTG)-based regimens are administered to women on Option B plus to prevent mother-to-child transmission (MTCT) of the virus. However, its effect on reducing MTCT of human immunodeficiency virus (HIV) among HIV-exposed infants over the previously used Efavirenz (EFV)-based regimen is unknown.
OBJECTIVE
This study aimed to compare the effects of DTG-based and EFV-based regimens on the MTCT of HIV among HIV-exposed infants in Ethiopia.
METHODS
An uncontrolled before-and-after study design was conducted among 958 mother-infant pairs (479 on EFV-based and 479 on DTG-based regimens) enrolled in the prevention of mother-to-child transmission (PMTCT) care from September 2015 to February 2023. The outcome variable was the HIV infection status among the exposed infants. A log-binomial model was employed, and the proportion was computed to compare the incidence of MTCT of HIV in both groups. The risk ratio (RR) with a 95% confidence interval (CI) was calculated to assess the predictor variables.
RESULTS
Mothers on DTG-based regimens were approximately 44% (adjusted risk ratio (aRR): 0.56; 95% CI: 0.44, 0.70) less likely to transmit HIV to their infants than those on EFV-based regimens. In addition, poor or fair adherence to antiretroviral therapy (ART) (aRR: 5.82; 95% CI: 3.41, 9.93), home delivery (aRR: 3.61; 95% CI: 2.32, 5.62), mixed feeding practice (aRR: 1.83; 95% CI: 1.45, 2.3) and not receiving antiretroviral prophylaxis (aRR: 3.26; 95% CI: 1.6, 6.64) were found to increase the risk of MTCT of HIV infection, whereas older maternal age (aRR: 0.93; 95% CI: 0.9, 0.96) was a protective factor.
CONCLUSION
Mother-to-child transmission of HIV was less frequently observed in mother-infant pairs exposed to the DTG-based regimens as compared to those exposed to the EFV-based regimens. Thus, DTG-based first-line ART regimens supplementation should be sustained to achieve global and national targets for zero new infections in HIV-exposed infants.
PubMed: 38765704
DOI: 10.2147/HIV.S456261 -
Contraception May 2024To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). (Review)
Review
OBJECTIVE
To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs).
DESIGN
Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality.
RESULTS
We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations.
CONCLUSION
Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.
PubMed: 38762199
DOI: 10.1016/j.contraception.2024.110490 -
AIDS Research and Therapy May 2024Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse...
BACKGROUND
Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas.
CASE PRESENTATION
A 55-year-old male had been on TDF/FTC/EFV for 8 years before switching to TAF/FTC/BIC. Nineteen months after antiretroviral switch, the patient presented with multiple lesions in the upper extremities and abdomen. Diagnostic biopsies revealed non-encapsulated angiolipomas and HHV-8 and non-alcoholic fatty liver disease was ruled out. New lesions continued to appear 29 months after ART switch, after which now lesions appeared and prior lesions remained stable with no increase in size noted. No surgical intervention or change in antiretroviral therapy was needed.
CONCLUSIONS
Angiogenesis may have been suppressed with TDF/FTC/EFV treatment, however when switched to TAF/FTC/BIC, promoted the growth of angiolipomas. Clinicians should be aware of the impact of switching to modern ART therapies resulting in possible adipogenesis.
Topics: Humans; Male; Middle Aged; HIV Infections; Angiolipoma; Tenofovir; Anti-HIV Agents; Drug Substitution; Antiretroviral Therapy, Highly Active
PubMed: 38734689
DOI: 10.1186/s12981-024-00620-9 -
Journal of Preventive Medicine and... Apr 2024This study investigated factors associated with the retention of people living with HIV on antiretroviral therapy (ART) during the first 3 years of treatment.
OBJECTIVES
This study investigated factors associated with the retention of people living with HIV on antiretroviral therapy (ART) during the first 3 years of treatment.
METHODS
A retrospective study using electronic health records was conducted at a tertiary hospital in Jakarta, Indonesia. Adult HIV-positive patients who started ART from 2010 until 2020 were included. A binary logistic regression model was used to identify factors associated with ART retention in the first 3 years.
RESULTS
In total, 535 respondents were included in the analysis. The ART retention rates for the first, second, and third years were 83.7%., 79.1%, and 77.2%, respectively. The multivariate analysis revealed a negative association between CD4 count when starting ART and retention. Patients with CD4 counts >200 cells/mL were 0.65 times less likely to have good retention than those with CD4 counts ≤ 200 cells/mL. The year of starting ART was also significantly associated with retention. Patients who started ART in 2010-2013 or 2014-2016 were less likely to have good retention than those who started ART in 2017-2020, with adjusted odds ratios of 0.52 and 0.40, respectively. Patients who received efavirenz-based therapy were 1.69 times more likely to have good retention than those who received nevirapine (95% CI, 1.05-2.72).
CONCLUSIONS
Our study revealed a decline in ART retention in the third year. The CD4 count, year of enrollment, and an efavirenz-based regimen were significantly associated with retention. Patient engagement has long been a priority in HIV programs, with interventions being implemented to address this issue.
PubMed: 38726581
DOI: 10.3961/jpmph.23.512 -
Journal of Lipid Research May 2024Cytochrome P450 46A1 (CYP46A1) is the CNS-specific cholesterol 24-hydroxylase that controls cholesterol elimination and turnover in the brain. In mouse models,...
Cytochrome P450 46A1 (CYP46A1) is the CNS-specific cholesterol 24-hydroxylase that controls cholesterol elimination and turnover in the brain. In mouse models, pharmacologic CYP46A1 activation with low-dose efavirenz or by gene therapy mitigates the manifestations of various brain disorders, neurologic, and nonneurologic, by affecting numerous, apparently unlinked biological processes. Accordingly, CYP46A1 is emerging as a promising therapeutic target; however, the mechanisms underlying the multiplicity of the brain CYP46A1 activity effects are currently not understood. We proposed the chain reaction hypothesis, according to which CYP46A1 is important for the three primary (unifying) processes in the brain (sterol flux through the plasma membranes, acetyl-CoA, and isoprenoid production), which in turn affect a variety of secondary processes. We already identified several processes secondary to changes in sterol flux and herein undertook a multiomics approach to compare the brain proteome, acetylproteome, and metabolome of 5XFAD mice (an Alzheimer's disease model), control and treated with low-dose efavirenz. We found that the latter had increased production of phospholipids from the corresponding lysophospholipids and a globally increased protein acetylation (including histone acetylation). Apparently, these effects were secondary to increased acetyl-CoA production. Signaling of small GTPases due to their altered abundance or abundance of their regulators could be affected as well, potentially via isoprenoid biosynthesis. In addition, the omics data related differentially abundant molecules to other biological processes either reported previously or new. Thus, we obtained unbiased mechanistic insights and identified potential players mediating the multiplicity of the CYP46A1 brain effects and further detailed our chain reaction hypothesis.
PubMed: 38719151
DOI: 10.1016/j.jlr.2024.100555 -
Bioscience Trends Apr 2024This study aimed to compare the efficacy and effect on lipid profiles of Ainuovirine (ANV)- and efavirenz (EFV) -based regimens in treatment-naïve people living with...
Efficacy and effect on lipid profiles of Ainuovirine-based regimen versus Efavirenz-based regimen in treatment-naïve people with HIV-1 at week 24: A real-world, retrospective, multi-center cohort study.
This study aimed to compare the efficacy and effect on lipid profiles of Ainuovirine (ANV)- and efavirenz (EFV) -based regimens in treatment-naïve people living with HIV-1 (PLWH) at week 24. The proportion of PLWH achieving HIV-1 RNA < the limit of quantification in the ANV group was significantly higher than that in the EFV group (89.18% vs. 76.04%, P = 0.002). The mean change of log HIV-1 RNA from baseline was greater (-4.34 vs. -4.18, P < 0.001), the median change from baseline in CD4+ T cell count increased more (106.00 cells/μL vs. 92.00 cells/μL, P = 0.007) in the ANV group, while the CD4+/CD8+ ratio was similar (0.15 vs. 0.20, P = 0.167) between the two groups. The mean changes from baseline in total cholesterol (-0.02 for ANV vs. 0.25 mmol/L for EFV, P < 0.001), triglyceride (-0.14 for ANV vs. 0.11 mmol/L for EFV, P = 0.024), and low-density lipoprotein cholesterol (-0.07 for ANV vs. 0.15 mmol/L for EFV, P < 0.001) was significantly different between the two groups. The percentage of patients with improved lipid profiles was significantly higher in the ANV group (37.44 %) than in the EFV group (29.55%, P = 0.0495). The incidence of any adverse events in the ANV group was significantly lower than that in the EFV group at week 12 (6.2% vs. 30.7%, P < 0.001) and was comparable at week 24 (3.6% vs. 5.5%, P = 0.28). The ANV-based regimen was well tolerated and lipid-friendly in treatment-naïve PLWH.
PubMed: 38684402
DOI: 10.5582/bst.2024.01070 -
Environmental Science and Pollution... May 2024This study focused on the efficacy of a calcined layered double hydroxide (CLDH) clay in adsorbing two antiretroviral drugs (ARVDs), namely efavirenz (EFV) and...
This study focused on the efficacy of a calcined layered double hydroxide (CLDH) clay in adsorbing two antiretroviral drugs (ARVDs), namely efavirenz (EFV) and nevirapine (NVP), from wastewater. The clay was synthesized using the co-precipitation method, followed by subsequent calcination in a muffle furnace at 500 °C for 4 h. The neat and calcined clay samples were subjected to various characterization techniques to elucidate their physical and chemical properties. Response surface modelling (RSM) was used to evaluate the interactions between the solution's initial pH, adsorbent loading, reaction temperature, and initial pollutant concentration. Additionally, the adsorption kinetics, thermodynamics, and reusability of the adsorbent were evaluated. The results demonstrated that NVP exhibited a faster adsorption rate than EFV, with both reaching equilibrium within 20-24 h. The pseudo-second order (PSO) model provided a good fit for the kinetics data. Thermodynamics analysis revealed that the adsorption process was spontaneous and exothermic, predominantly governed by physisorption interactions. The adsorption isotherms followed the Freundlich model, and the maximum adsorption capacities for EFV and NVP were established to be 2.73 mg/g and 2.93 mg/g, respectively. Evaluation of the adsorption mechanism through computational analysis demonstrated that both NVP and EFV formed stable complexes with CLDH, with NVP exhibiting a higher affinity. The associated adsorption energies were established to be -731.78 kcal/mol for NVP and -512.6 kcal/mol for EFV. Visualized non-covalent interaction (NCI) graphs indicated that hydrogen bonding played a significant role in ARVDs-CLDH interactions, further emphasizing physisorption as the dominant adsorption mechanism.
Topics: Adsorption; Clay; Kinetics; Hydroxides; Thermodynamics; Anti-Retroviral Agents; Water Pollutants, Chemical; Benzoxazines; Wastewater; Alkynes; Cyclopropanes
PubMed: 38649603
DOI: 10.1007/s11356-024-33406-7