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1.
Ghana Med J ; 58(1): 101-108, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38957273

ABSTRACT

Objective: To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy. Design: This was a retrospective chart review. Setting: A tertiary health facility-based study in Abakaliki, Nigeria. Participants: Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25. Main outcome measures: Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated. Results: The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m2, and a 2.6% increase in the prevalence of overweight and obesity. Conclusions: Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain. Funding: None declared.


Subject(s)
Body Mass Index , HIV Infections , HIV Integrase Inhibitors , Heterocyclic Compounds, 3-Ring , Medication Adherence , Oxazines , Piperazines , Pyridones , Tertiary Care Centers , Humans , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Female , Male , Middle Aged , Retrospective Studies , HIV Infections/drug therapy , Adult , Nigeria , Medication Adherence/statistics & numerical data , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/adverse effects , Viral Load , Treatment Outcome
3.
Medicine (Baltimore) ; 103(27): e38558, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968505

ABSTRACT

Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTG + 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTG + 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTG + 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loads < 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA level ≥ 1 × 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4 + cell count of <200 cells/µL achieved virological suppression. The median CD4 + cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTG + 3TC. Using DTG + 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.


Subject(s)
Anti-HIV Agents , Drug Therapy, Combination , HIV Infections , Heterocyclic Compounds, 3-Ring , Lamivudine , Oxazines , Piperazines , Pyridones , Tuberculosis , Humans , Pyridones/administration & dosage , Pyridones/therapeutic use , Pyridones/adverse effects , Lamivudine/therapeutic use , Lamivudine/administration & dosage , Lamivudine/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Female , HIV Infections/drug therapy , HIV Infections/complications , Male , Retrospective Studies , Adult , Piperazines/therapeutic use , Piperazines/administration & dosage , Piperazines/adverse effects , China , Middle Aged , Tuberculosis/drug therapy , Tuberculosis/complications , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects , Anti-HIV Agents/administration & dosage , Viral Load/drug effects , Coinfection/drug therapy , Treatment Outcome , CD4 Lymphocyte Count
4.
FASEB J ; 38(13): e23790, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38982638

ABSTRACT

Integrase strand transfer inhibitors (INSTIs) based antiretroviral therapy (ART) is currently used as first-line regimen to treat HIV infection. Despite its high efficacy and barrier to resistance, ART-associated neuropsychiatric adverse effects remain a major concern. Recent studies have identified a potential interaction between the INSTI, dolutegravir (DTG), and folate transport pathways at the placental barrier. We hypothesized that such interactions could also occur at the two major blood-brain interfaces: blood-cerebrospinal fluid barrier (BCSFB) and blood-brain barrier (BBB). To address this question, we evaluated the effect of two INSTIs, DTG and bictegravir (BTG), on folate transporters and receptor expression at the mouse BCSFB and the BBB in vitro, ex vivo and in vivo. We demonstrated that DTG but not BTG significantly downregulated the mRNA and/or protein expression of folate transporters (RFC/SLC19A1, PCFT/SLC46A1) in human and mouse BBB models in vitro, and mouse brain capillaries ex vivo. Our in vivo study further revealed a significant downregulation in Slc19a1 and Slc46a1 mRNA expression at the BCSFB and the BBB following a 14-day DTG oral treatment in C57BL/6 mice. However, despite the observed downregulatory effect of DTG in folate transporters/receptor at both brain barriers, a 14-day oral treatment of DTG-based ART did not significantly alter the brain folate level in animals. Interestingly, DTG treatment robustly elevated the mRNA and/or protein expression of pro-inflammatory cytokines and chemokines (Cxcl1, Cxcl2, Cxcl3, Il6, Il23, Il12) in primary cultures of mouse brain microvascular endothelial cells (BBB). DTG oral treatment also significantly upregulated proinflammatory cytokines and chemokine (Il6, Il1ß, Tnfα, Ccl2) at the BCSFB in mice. We additionally observed a downregulated mRNA expression of drug efflux transporters (Abcc1, Abcc4, and Abcb1a) and tight junction protein (Cldn3) at the CP isolated from mice treated with DTG. Despite the structural similarities, BTG only elicited minor effects on the markers of interest at both the BBB and BCSFB. In summary, our current data demonstrates that DTG but not BTG strongly induced inflammatory responses in a rodent BBB and BCSFB model. Together, these data provide valuable insights into the mechanism of DTG-induced brain toxicity, which may contribute to the pathogenesis of DTG-associated neuropsychiatric adverse effect.


Subject(s)
Blood-Brain Barrier , Heterocyclic Compounds, 3-Ring , Oxazines , Piperazines , Pyridones , Animals , Mice , Piperazines/pharmacology , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Oxazines/pharmacology , Inflammation/chemically induced , Inflammation/metabolism , Mice, Inbred C57BL , Female , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/adverse effects , HIV Infections/drug therapy , HIV Infections/metabolism , Male , Anti-Retroviral Agents/adverse effects , Brain/metabolism , Brain/drug effects
5.
Sci Rep ; 14(1): 16004, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992288

ABSTRACT

The formation of symbionts by using different combinations of endophytic bacteria, microalgae, and fungi to purify antibiotics-containing wastewater is an effective and promising biomaterial technology. As it enhances the mixed antibiotics removal performance of the bio-system, this technology is currently extensively studied. Using exogenous supplementation of various low concentrations of the phytohormone strigolactone analogue GR24, the removal of various antibiotics from simulated wastewater was examined. The performances of Chlorella vulgaris monoculture, activated sludge-C. vulgaris-Clonostachys rosea, Bacillus licheniformis-C. vulgaris-C. rosea, and endophytic bacteria (S395-2)-C. vulgaris-C. rosea co-culture systems were systematically compared. Their removal capacities for tetracycline, oxytetracycline, and chlortetracycline antibiotics from simulated wastewater were assessed. Chlorella vulgaris-endophytic bacteria-C. rosea co-cultures achieved the best performance under 0.25 mg L-1 antibiotics, which could be further enhanced by GR24 supplementation. This result demonstrates that the combination of endophytic bacteria with microalgae and fungi is superior to activated sludge-B. licheniformis-microalgae-fungi systems. Exogenous supplementation of GR24 is an effective strategy to improve the performance of antibiotics removal from wastewater.


Subject(s)
Anti-Bacterial Agents , Microalgae , Microalgae/metabolism , Anti-Bacterial Agents/pharmacology , Chlorella vulgaris/metabolism , Coculture Techniques , Lactones/metabolism , Wastewater/chemistry , Wastewater/microbiology , Heterocyclic Compounds, 3-Ring/isolation & purification , Sewage/microbiology , Water Pollutants, Chemical , Biodegradation, Environmental , Water Purification/methods
7.
Front Immunol ; 15: 1416004, 2024.
Article in English | MEDLINE | ID: mdl-39044833

ABSTRACT

Introduction: Conventional rosacea treatments are not uniformly pervasive, and the adverse reactions can potentially constrain their utility. The clinical use of JAK1 inhibitors upadacitinib and abrocitinib in the treatment of refractory rosacea has rarely been explored. Case report: We presented two cases of patients who received the JAK1 inhibitor upadacitinib and four cases of patients who received the JAK1 inhibitor abrocitinib for the treatment of refractory rosacea. Discussion: The JAK1 inhibitors upadacitinib and abrocitinib may be promising medical options for patients with refractory rosacea. However, the long-term safety and efficacy of upadacitinib and abrocitinib require prospective controlled studies to assess them more comprehensively.


Subject(s)
Heterocyclic Compounds, 3-Ring , Janus Kinase Inhibitors , Rosacea , Humans , Rosacea/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Female , Middle Aged , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Sulfonamides/therapeutic use , Male , Treatment Outcome , Adult , Janus Kinase 1/antagonists & inhibitors
8.
Sci Rep ; 14(1): 16785, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039129

ABSTRACT

A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80- < 90%, and < 80% groups, respectively. Across all PDC groups, more than 90% of patients who received B/F/TAF were receiving treatment at 1 year. There was no significant difference in the risk of discontinuation between the lower PDC groups (80- < 90% and < 80%) and the PDC ≥ 90% group (0.400 [0.096, 1.661]; 2.244 [0.663, 7.594], hazard ratio [95% confidence interval], respectively). A drug resistance test was implemented for 15 patients, none of whom discontinued B/F/TAF after the test. The results suggest that events that could cause discontinuation, such as virologic failure, were not associated with PDC.


Subject(s)
Alanine , Anti-HIV Agents , Emtricitabine , HIV Infections , Medication Adherence , Pyridones , Tenofovir , Humans , Tenofovir/therapeutic use , Tenofovir/analogs & derivatives , Male , Female , HIV Infections/drug therapy , HIV Infections/virology , Emtricitabine/therapeutic use , Japan , Middle Aged , Retrospective Studies , Adult , Anti-HIV Agents/therapeutic use , Alanine/therapeutic use , Alanine/analogs & derivatives , Pyridones/therapeutic use , Piperazines/therapeutic use , Treatment Outcome , Amides/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Adenine/analogs & derivatives , Adenine/therapeutic use , Databases, Factual , Drug Combinations
9.
BMC Infect Dis ; 24(1): 720, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39039487

ABSTRACT

BACKGROUND: Antiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens. METHODS: A retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed. RESULTS: The study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported. CONCLUSIONS: DTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH.


Subject(s)
Anti-HIV Agents , HIV Infections , Heterocyclic Compounds, 3-Ring , Lamivudine , Oxazines , Pyridones , Viral Load , Humans , Retrospective Studies , HIV Infections/drug therapy , HIV Infections/virology , Viral Load/drug effects , Female , Male , Pyridones/therapeutic use , Lamivudine/therapeutic use , Lamivudine/administration & dosage , Adult , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , Oxazines/therapeutic use , Middle Aged , CD4 Lymphocyte Count , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Piperazines/therapeutic use , HIV-1/drug effects , Drug Therapy, Combination , RNA, Viral/blood , Treatment Outcome
10.
J Int AIDS Soc ; 27(7): e26268, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38978403

ABSTRACT

INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.


Subject(s)
Blood Pressure , HIV Infections , Hypertension , Tenofovir , Weight Gain , Humans , Male , Female , South Africa , HIV Infections/drug therapy , Adult , Middle Aged , Tenofovir/therapeutic use , Tenofovir/adverse effects , Tenofovir/analogs & derivatives , Weight Gain/drug effects , Hypertension/drug therapy , Blood Pressure/drug effects , Blood Pressure/physiology , Pyridones/therapeutic use , Piperazines/therapeutic use , Oxazines/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Glomerular Filtration Rate/drug effects , Alanine/therapeutic use , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects
11.
AIDS Res Ther ; 21(1): 45, 2024 07 10.
Article in English | MEDLINE | ID: mdl-38987825

ABSTRACT

BACKGROUND: The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. METHODS: Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. RESULTS: All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. CONCLUSIONS: RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.


Subject(s)
Anti-HIV Agents , Emtricitabine , HIV Infections , Tenofovir , Humans , HIV Infections/drug therapy , Pilot Projects , Male , Female , Adult , Tenofovir/therapeutic use , Tenofovir/administration & dosage , Tenofovir/analogs & derivatives , Middle Aged , Anti-HIV Agents/therapeutic use , Emtricitabine/therapeutic use , Emtricitabine/administration & dosage , Alanine/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , HIV-1/drug effects , Piperazines/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Viral Load/drug effects , Amides/therapeutic use , RNA, Viral/blood , Pyridones
12.
Sci Rep ; 14(1): 16290, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009738

ABSTRACT

Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , Piperazines , Polymorphism, Single Nucleotide , Humans , HEK293 Cells , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Piperazines/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Amides/metabolism , Pyridones/metabolism , Heterocyclic Compounds, 4 or More Rings/metabolism
13.
Clin Rheumatol ; 43(8): 2503-2511, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38954278

ABSTRACT

Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.


Subject(s)
Adrenal Cortex Hormones , Arthritis, Rheumatoid , Azetidines , Herpes Zoster , Janus Kinase Inhibitors , Humans , Arthritis, Rheumatoid/drug therapy , Herpes Zoster/chemically induced , Herpes Zoster/prevention & control , Herpes Zoster/epidemiology , Retrospective Studies , Male , Female , Middle Aged , Aged , Janus Kinase Inhibitors/adverse effects , Janus Kinase Inhibitors/therapeutic use , Risk Factors , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Azetidines/adverse effects , Azetidines/therapeutic use , Sulfonamides/adverse effects , Sulfonamides/administration & dosage , Sulfonamides/therapeutic use , Piperidines/adverse effects , Piperidines/therapeutic use , Piperidines/administration & dosage , Incidence , Pyrazoles/adverse effects , Purines/adverse effects , Pyrimidines/adverse effects , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , COVID-19/epidemiology , Adult , SARS-CoV-2 , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use
14.
Front Public Health ; 12: 1385441, 2024.
Article in English | MEDLINE | ID: mdl-39015389

ABSTRACT

Background: The effect of dolutegravir (DTG)-based regimens on reducing attrition from care among women enrolled in the prevention of mother-to-child transmission (PMTCT) care program is unknown. Therefore, this study aimed to compare the incidence of attrition among women exposed to DTG-based with those exposed to efavirenz (EFV)-based first-line antiretroviral therapy (ART) in Ethiopia. Methods: An uncontrolled before-and-after study was conducted involving 932 women (with 466 on EFV-based and 466 on DTG-based regimens) who were enrolled in the PMTCT care program from September 2015 to February 2023. The outcome variable was attrition (i.e., maternal death or loss to follow-up before their infants' final HIV status was determined). A Kaplan-Meier estimator was employed to estimate the probability of attrition. The Cox proportional hazards regression model was fitted to identify predictor variables. The adjusted hazard ratio (aHR) with the corresponding 95% confidence interval (CI) was calculated to examine the risk difference in the comparison groups. Results: The cumulative incidence of attrition among women was 5.2% (3.0% for those placed in the DTG-based regimen arm and 7.3% for those placed in the EFV-based regimen arm). Women on DTG-based regimens had a 57% (aHR: 0.43; 95% CI: 0.23-0.80) lower risk of attrition from care compared to those on EFV-based regimens. Women who delivered their infants at home (aHR: 2.35; 95% CI: 1.14-4.85), had poor/fair adherence (aHR: 3.23; 95% CI: 1.62-6.45), had unsuppressed/unknown viral load status (aHR: 2.61; 95% CI: 1.42-4.79), and did not disclose their status to partners (aHR: 2.56; 95% CI: 1.34-4.92) had a higher risk of attrition from PMTCT care compared to their counterparts. Conclusion: The cumulative incidence of attrition among women receiving PMTCT care is optimal. In addition, the risk of attrition among women receiving DTG-based regimens is lower than that among women receiving EFV-based regimens. Thus, DTG-based first-line ART regimen supplementation should be sustained to achieve a national retention target of 95% and above.


Subject(s)
Alkynes , Benzoxazines , Cyclopropanes , HIV Infections , Heterocyclic Compounds, 3-Ring , Infectious Disease Transmission, Vertical , Oxazines , Piperazines , Pyridones , Humans , Female , Ethiopia/epidemiology , Benzoxazines/therapeutic use , Adult , HIV Infections/drug therapy , HIV Infections/epidemiology , Heterocyclic Compounds, 3-Ring/therapeutic use , Pregnancy , Infectious Disease Transmission, Vertical/prevention & control , Anti-HIV Agents/therapeutic use , Young Adult , Medication Adherence/statistics & numerical data , Adolescent
15.
Pediatr Infect Dis J ; 43(8): 789-794, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39018516

ABSTRACT

INTRODUCTION: Dolutegravir (DTG) dispersible tablet (DTG-DT) is a pediatric-friendly formulation. We aimed to describe the pharmacokinetics and virologic responses of generic DTG-DT in children weighing <20 kg. METHODS: Children living with HIV-1 and <7 years of age weighing 6 to <20 kg were eligible. A generic 10-mg scored DTG-DT was administered to children using 3 weight bands (WB): WB1 (6 to <10 kg), WB2 (10 to <14 kg) and WB3 (14 to <20 kg), at doses of 20 mg (higher than World Health Organization recommendation of 15 mg), 20 mg and 25 mg, respectively. Steady-state intensive pharmacokinetics (PK) was performed in fasting condition with blood sampling at predose and 1, 2, 3, 4, 6 and 24 hours postdose. DTG PK parameters were estimated using a noncompartmental analysis, and DTG trough concentrations (C 24 ) and 24-hour area under the concentration-time curve were calculated. Comparisons were made with ODYSSEY and IMPAACT 2019. And 90% effective concentration of 0.32 mg/L was used as a reference individual DTG C 24 concentration. RESULTS: From August 2021 to March 2023, 29 Thai children with a median (interquartile range) age of 3.2 (1.5-4.8) years were enrolled; 8 in WB1, 9 in WB2 and 12 in WB3. All children were treatment experienced and 59% had HIV RNA <200 copies/mL. Overall geometric mean (coefficient of variation percentage) DTG C 24 was 1.0 (46%) mg/L [WB1, 0.9 (53%); WB2, 0.9 (27%); WB3, 1.2 (51%)]. Geometric mean (coefficient of variation percentage) 24-hour area under the concentration-time curve was 83.2 (24%) mg h/L [WB1, 84.3 (31%); WB2, 76.9 (16%); WB3, 87.6 (25%)]. At weeks 24 and 48, 90% and 92% of participants had plasma HIV RNA <200 copies/mL. CONCLUSIONS: Generic DTG-DT provided adequate drug exposure in children weighing 6 to <20 kg. The exploratory dose of DTG 20 mg for children weighing 6 to <10 kg showed similar PK parameters to World Health Organization doses in the other WB.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , Heterocyclic Compounds, 3-Ring , Child , Child, Preschool , Female , Humans , Infant , Male , Body Weight , Drugs, Generic/pharmacokinetics , Heterocyclic Compounds, 3-Ring/pharmacokinetics , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/administration & dosage , HIV Infections/drug therapy , HIV Integrase Inhibitors/pharmacokinetics , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/administration & dosage , Oxazines , Piperazines , Pyridones , Southeast Asian People , Tablets , Thailand , Viral Load
16.
Rev Gastroenterol Peru ; 44(2): 162-166, 2024.
Article in Spanish | MEDLINE | ID: mdl-39019812

ABSTRACT

Crohn's disease (CD) is a chronic, progressive inflammatory disease with complications that impact the well-being of patients. The therapeutic advances achieved in recent decades, especially through the advent of biological therapy, have allowed for a transformation in the approach and management of CD, thereby modifying the course of this disease. However, a significant number of patients do not experience a satisfactory response to these drugs or lose it during the course of the disease. In this scenario, a viable alternative is to switch medications. Upadacitinib, a novel Janus kinase inhibitor, has emerged as a promising strategy for the management of CD. We presented two cases of patients with CD refractory to conventional therapy and biological therapy, who responded successfully to treatment with upadacitinib.


Subject(s)
Crohn Disease , Heterocyclic Compounds, 3-Ring , Humans , Crohn Disease/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Adult , Female , Male , Janus Kinase Inhibitors/therapeutic use
17.
PLoS One ; 19(7): e0306714, 2024.
Article in English | MEDLINE | ID: mdl-38990897

ABSTRACT

BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. METHODS: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. RESULTS: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). CONCLUSIONS: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.


Subject(s)
Arthritis, Rheumatoid , Azetidines , Janus Kinase Inhibitors , Piperidines , Purines , Pyrazoles , Sulfonamides , Humans , Arthritis, Rheumatoid/drug therapy , Male , Female , Middle Aged , Janus Kinase Inhibitors/therapeutic use , Janus Kinase Inhibitors/adverse effects , Azetidines/therapeutic use , Azetidines/adverse effects , Retrospective Studies , Aged , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Purines/therapeutic use , Purines/adverse effects , Sulfonamides/therapeutic use , Sulfonamides/adverse effects , Piperidines/therapeutic use , Piperidines/adverse effects , Pyrimidines/therapeutic use , Pyrimidines/adverse effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Triazoles/therapeutic use , Triazoles/adverse effects , Risk Factors , Adult , Pyridines
18.
BMC Infect Dis ; 24(1): 665, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961336

ABSTRACT

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1ß, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell's median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1ß, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.


Subject(s)
Cytokines , HIV Infections , Heterocyclic Compounds, 3-Ring , Oxazines , Piperazines , Pyridones , Humans , HIV Infections/drug therapy , Cytokines/blood , Male , Female , Adult , Middle Aged , Heterocyclic Compounds, 3-Ring/therapeutic use , Heterocyclic Compounds, 3-Ring/adverse effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Oxazines/therapeutic use , Piperazines/therapeutic use , Piperazines/administration & dosage , Pyridones/therapeutic use , Pyridones/administration & dosage , Viral Load/drug effects , Drug Therapy, Combination , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count
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