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OBJECTIVE: This study examined the prevalence, severity and risk factors of anaemia among adult people living with HIV attending an antiretroviral therapy centre in Woreta Primary Hospital, Woreta town, Ethiopia. DESIGN: Hospital-based retrospective cross-sectional study. SETTING: Public health facility that provides HIV care in Woreta town. PARTICIPANTS: A total of 289 medical records of adults living with HIV/AIDS on highly active antiretroviral therapy from February 2019 to September 2023 at government hospital were reviewed using a systematic sampling method. The data were entered using Epi-info V.7 and exported to SPSS V.23 for data analysis. The data were analysed using bivariate and then multivariate logistic regression models in order to identify variables associated with anaemia. At the 95% CI level, variables having a p value of <0.05 were deemed to be statistically significant predictors. PRIMARY OUTCOME: Prevalence and severity of anaemia and its predictors among adult patients living with HIV on antiretroviral therapy in Woreta Primary Hospital. RESULTS: The total prevalence of anaemia was 31.5% (95% CI 28.9 to 33.8). The prevalence of mild, moderate and severe anaemia was 20.42%, 10.38% and 0.70%, respectively. Predictors independently linked with anaemia were female sex (adjusted OR (AOR) 1.08), age ≥40 years (AOR 1.21), lived with HIV >10 years (AOR 2.31), CD4 counts <200 cells/µL (AOR 3.81), non-suppressed viral load (AOR 1.28), history of opportunistic infections (AOR 1.54), WHO clinical stages III and IV (AOR 1.37 and 2.23, respectively) and history of parasitic infestation (AOR 2.81). CONCLUSIONS: A sizeable proportion of participants were found anaemic. Female sex, older age, longer periods lived with the virus, lower CD4 count, non-suppressed viral load, history of opportunistic infections, WHO clinical stages III and IV and history of parasitic infestation were the contributing factors. Therefore, to improve the anaemic status and living circumstances of patients living with HIV, immediate action on the linked factors is needed, such as monitoring for maintenance of CD4 counts >200 cells/µL and avoiding progression of HIV to the advanced WHO clinical stages, suppressed viral load, preventing opportunistic infections and parasitic infestation.
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Anemia , Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piridonas , Humanos , Femenino , Masculino , Adulto , Estudios Transversales , Estudios Retrospectivos , Anemia/epidemiología , Etiopía/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prevalencia , Persona de Mediana Edad , Factores de Riesgo , Piridonas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Recuento de Linfocito CD4 , Adulto Joven , Inhibidores de Integrasa VIH/uso terapéutico , Índice de Severidad de la Enfermedad , PiperazinasAsunto(s)
Fármacos Anti-VIH , Farmacorresistencia Viral , Emtricitabina , Infecciones por VIH , VIH-1 , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Piridonas , Tenofovir , Humanos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Emtricitabina/uso terapéutico , Piridonas/uso terapéutico , Piperazinas/uso terapéutico , Tenofovir/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Oxazinas/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Hepatitis B/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/uso terapéutico , Masculino , Femenino , AmidasAsunto(s)
Alopecia , Colitis Ulcerosa , Compuestos Heterocíclicos con 3 Anillos , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Alopecia/tratamiento farmacológico , Alopecia/etiología , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , AdultoRESUMEN
BACKGROUND: An increase in the prevalence of HIV drug resistance (HIVDR) has been reported in recent years, especially in persons on non-nucleoside reverse transcriptase inhibitors (NNRTIs) due to their low genetic barrier to mutations. However, there is a paucity of epidemiological data quantifying HIVDR in the era of new drugs like dolutegravir (DTG) in sub-Saharan Africa. We, therefore, sought to determine the prevalence and correlates of viral load (VL) suppression in adult people with HIV (PWH) on a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) or tenofovir alafenamide/emtricitabine/dolutegravir (TAFED) and describe patterns of mutations in individuals failing treatment. METHODS: We conducted a cross-sectional study among 384 adults living with HIV aged ≥15 years between 5th June 2023 and 10th August 2023. Demographic, laboratory and clinical data were collected from electronic health records using a data collection form. Viral load suppression was defined as plasma HIV-1 RNA VL of <1000 copies/ml after being on ART for ≥ 6 months. SPSS version 22 to analyze the data. Descriptive statistics and logistic regression were the statistical methods used. RESULTS: The median (interquartile range (IQR)) age was 22 (IQR 18, 38) years, and 66.1% (n = 254) were females. VL suppression was 90.4% (n = 347); (95% confidence interval (CI) 87.6%-93.6%) after switching to TLD/TAFED. Among the virally suppressed, the majority (67.1%, n = 233) were female. Those who missed ≥2 doses in the last 30 days prior to the most recent review were less likely to attain viral suppression compared to those who did not miss any dose (adjusted odds ratio (AOR) 0.047; 95% CI 0.016-0.136; p<0.001). Four participants had resistance mutations to lamivudine and tenofovir. The most common NRTI mutations were M184MV and K65R while K101E was the most common NNRTI mutation. CONCLUSION: Our findings show that viral suppression was high after switching to TLD/TAFED; but lower than the last 95% target of the UNAIDS. Adherence to antiretroviral therapy was a significant correlate of VL suppression. We, therefore, recommend prompt switching of PWH to TLD/TAFED regimen and close monitoring to enhance adherence to therapy.
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Fármacos Anti-VIH , Farmacorresistencia Viral , Infecciones por VIH , VIH-1 , Lamivudine , Mutación , Piperazinas , Piridonas , Tenofovir , Carga Viral , Humanos , Femenino , Adulto , VIH-1/genética , VIH-1/efectos de los fármacos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Farmacorresistencia Viral/genética , Carga Viral/efectos de los fármacos , Zambia/epidemiología , Estudios Transversales , Tenofovir/uso terapéutico , Tenofovir/farmacología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Piperazinas/uso terapéutico , Lamivudine/uso terapéutico , Lamivudine/farmacología , Piridonas/uso terapéutico , Oxazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/farmacología , Emtricitabina/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Adolescente , Combinación de MedicamentosRESUMEN
BACKGROUND: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting. SETTING: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory. METHODS: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test. RESULTS: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log10 HIV-RNA was 4.79 (± 0.87) log10 copies/mL and CD4 505 (±253) cells/mm3. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log10 copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. CONCLUSION: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.
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Fármacos Anti-VIH , Emtricitabina , Infecciones por VIH , Tenofovir , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Femenino , Adulto , Tenofovir/uso terapéutico , Tenofovir/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , VIH-1/genética , Adenina/análogos & derivados , Adenina/uso terapéutico , Piperazinas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Darunavir/uso terapéutico , Alanina/uso terapéutico , Alanina/análogos & derivados , Resultado del Tratamiento , ARN Viral , Sulfonamidas/uso terapéutico , Persona de Mediana Edad , Cobicistat/uso terapéutico , Reino Unido , Combinación de Medicamentos , Amidas , PiridonasRESUMEN
BACKGROUND: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. METHODS: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. DISCUSSION: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. TRIAL REGISTRATION: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538.
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Adalimumab , Ansiedad , Artritis Psoriásica , Compuestos Heterocíclicos con 3 Anillos , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/psicología , Adalimumab/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/diagnóstico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: A dolutegravir (DTG)-based antiretroviral regimen has been rolled out for pregnant women in low- and middle-income countries since 2020. However, available safety data are limited to a few clinical trials and observational studies. Hence, we present real-world pregnancy and birth outcome safety data from a large sample multicenter cohort study in Ethiopia. METHODS: A retrospective cohort study was conducted in fourteen hospitals across Ethiopia from 2017 to 2022. HIV-infected pregnant women were followed from the date of prevention of mother-to-child transmission (PMTCT) care enrolment until the infant was 6-8 weeks old. The primary safety outcome was a composite of adverse pregnancy events comprising spontaneous abortion, intrauterine fetal death (IUFD) before onset of labor, preterm birth, and maternal death. Additionally, a composite adverse birth outcome was assessed, comprising intrapartum fetal demise, low birth weight, and neonatal death. Finally, a composite of adverse pregnancy or birth outcome was also investigated. The exposure of interest was the antiretroviral treatment (ART) regimen used during pregnancy for PMTCT of HIV. RESULTS: During the study period, 2643 women were enrolled in routine PMTCT care. However, 2490 (92.2%) participants were eligible for the study. A total of 136/1724 (7.9%, 95% CI: 6.7-9.3%) women experienced adverse pregnancy outcomes. Fewer women in the DTG-based group (5.4%, 95% CI: 3.7-7.5%) had adverse pregnancy outcomes than in the Efavirenz (EFV)-based group (8.3%, 95% CI: 6.6-10.3%), P = 0.004. After controlling for baseline differences, the DTG group had a 43% lower risk of adverse pregnancy outcomes (adjusted odd ratio (AOR), 0.57; 95% CI, 0.32-0.96%) and a 53% lower risk of preterm birth (AOR, 0.47; 95% CI, 0.22-0.98%) compared to the EFV group. A total of 103/1616 (6.4%, 95% CI: 5.2-7.7%) women had adverse birth outcomes. Although the difference was not statistically significant, fewer women in the DTG group (30/548; 5.5%, 95% CI: 3.7-7.7%) than in the EFV group (57/830; 6.9%, 95% CI: 5.2-8.8%) had adverse birth outcomes. CONCLUSIONS: In this study, we observed that DTG-based regimens were associated with better pregnancy and birth outcome safety profiles, reaffirming the WHO recommendation. However, a prospective study is recommended to assess uncaptured maternal and perinatal adverse outcomes, such as congenital abnormalities, and infant growth and neurocognitive development.
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Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Transmisión Vertical de Enfermedad Infecciosa , Oxazinas , Piperazinas , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , Piridonas , Humanos , Embarazo , Femenino , Etiopía/epidemiología , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Adulto , Estudios Retrospectivos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Adulto Joven , Ciclopropanos , Benzoxazinas/uso terapéutico , Benzoxazinas/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Alquinos , Estudios de Cohortes , Nacimiento Prematuro/epidemiologíaRESUMEN
Purpose: Amyopathic dermatomyositis (ADM) is a rare, idiopathic, connective tissue disease and melanoma differentiation-associated protein 5 (MDA5) antibody-positive ADM is more treatment-resistant, especially in patients with interstitial lung disease (ILD). The purpose of this article is to report a case of anti-MDA5-positive ADM successfully treated with JAK inhibitor Upadacitinib.Materials and methods: A 35-year-old Chinese woman presented with recurrent itchy erythema on her face and scalp for 4 years. Upon examination, there were heliotrope erythema and eyelid edema, reddish rash on neck and scalp. Biopsy of the lesions was consistent with DM and a line blot assay confirmed the presence of anti-MDA5 antibodies. This patient was treated with oral Upadacitinib at a dosage of 30 mg daily.Results: After 6 weeks of treatment, she achieved complete clinical remission with no reported side effects or instances of relapse. The antibody titer of anti-MDA5 was also decreased.Conclusions: Upadacitinib may be a potential drug candidate in patients with treatment-resistant ADM, especially in cases with refractory cutaneous conditions.
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Dermatomiositis , Compuestos Heterocíclicos con 3 Anillos , Helicasa Inducida por Interferón IFIH1 , Humanos , Femenino , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/patología , Helicasa Inducida por Interferón IFIH1/inmunología , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Resultado del Tratamiento , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificaciónRESUMEN
INTRODUCTION: This study compared the clinical effectiveness of switching from tumor necrosis factor inhibitor (TNFi) to upadacitinib (TNFi-UPA), another TNFi (TNFi-TNFi), or an advanced therapy with another mechanism of action (TNFi-other MOA) in patients with rheumatoid arthritis (RA). METHODS: Data were drawn from the Adelphi RA Disease Specific Programme™, a cross-sectional survey administered to rheumatologists and their consulting patients in Germany, France, Italy, Spain, the UK, Japan, Canada, and the USA from May 2021 to January 2022. Patients who switched treatment from an initial TNFi were stratified by subsequent therapy of interest: TNFi-UPA, TNFi-TNFi, or TNFi-other MOA. Physician-reported clinical outcomes including disease activity (with formal DAS28 scoring available for 29% of patients) categorized as remission, low/moderate/high disease activity, as well as pain were recorded at initiation of current treatment and ≥ 6 months from treatment switch. Fatigue and treatment adherence were measured ≥ 6 months from treatment switch. Inverse-probability-weighted regression adjustment compared outcomes by subsequent class of therapy: TNFi-UPA versus TNFi-TNFi, or TNFi-UPA versus TNFi-other MOA. RESULTS: Of 503 patients who switched from their first TNFi, 261 were in TNFi-UPA, 128 in TNFi-TNFi, and 114 in TNFi-other MOA groups. At the time of switch, most patients had moderate/high disease activity (TNFi-UPA: 73%; TNFi-TNFi: 52%; TNFi-other MOA: 60%). After adjustment for differences in characteristics at point of switch, patients in TNFi-UPA group (n = 261) were significantly more likely to achieve physician-reported remission (67.7% vs. 40.3%; p = 0.0015), no pain (55.7% vs. 25.4%; p = 0.0007), and complete adherence (60.0% vs. 34.2%; p = 0.0049) compared with patients in TNFi-TNFi group (n = 121). Similar findings were observed for TNFi-UPA versus TNFi-other MOA groups (n = 111). CONCLUSION: Patients who switched from TNFi to UPA had significantly better clinical outcomes of remission, no pain, and complete adherence than those who cycled TNFi or switched to another MOA.
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Antirreumáticos , Artritis Reumatoide , Compuestos Heterocíclicos con 3 Anillos , Inhibidores del Factor de Necrosis Tumoral , Humanos , Artritis Reumatoide/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Estudios Transversales , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Resultado del Tratamiento , Anciano , Sustitución de Medicamentos/estadística & datos numéricos , Adulto , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Millions of people living with HIV (PLWH) take oral antiretroviral therapy (ART), which requires a lifetime of consistent medication adherence. The relationship between adherence and poor HIV outcomes is well documented. Newer ART regimens that include dolutegravir (DTG) could be more forgiving, but empirical evidence on the relationship between adherence and viral suppression under DTG is only emerging. METHODS: In this observational cohort study (secondary analysis of data from a randomized trial), we used data from 313 ART clients from a large HIV clinic in Kampala, Uganda. Over the 4-year study period (January 2018-January 2022), 91% switched from non-DTG regimens to DTG regimens. We measured adherence using Medication Event Monitoring Systems-caps and extracted prescription information and viral load measures from electronic health records. We estimated unadjusted linear regressions and adjusted models that included individual and time fixed-effects. RESULTS: Under non-DTG regimens, 96% of participants were virally suppressed (defined as viral load < 200 copies/ml) when adherence was 90% or higher in the 3 months before viral load measurement. Viral suppression was 32 percentage points lower when adherence was between 0% and 49% (95% CI -0.44, -0.20, p < 0.01), 12 percentage points lower when adherence was between 50% and 79% (95% CI -0.23, -0.02, p < 0.01), and not significantly different when adherence was between 80% and 89% (effect of 0.00, 95% CI -0.06, 0.07, p = 0.81). In contrast, for participants taking DTG, there was no statistically significant difference in viral suppression among any of the four adherence levels; more than 95% were virally suppressed at each adherence level. On average, switching to DTG increased viral suppression by 6 percentage points in our adjusted models (95% CI 0.00, 0.13, p = 0.03). CONCLUSIONS: There was no significant association between adherence levels and viral suppression among PLWH taking DTG regimens, suggesting a high degree of forgiveness for missed doses. The use of DTG should be prioritized over older regimens, particularly for those with low adherence. CLINICAL TRIAL NUMBER: NCT03494777.
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Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Cumplimiento de la Medicación , Oxazinas , Piperazinas , Piridonas , Carga Viral , Humanos , Uganda , Piridonas/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Femenino , Cumplimiento de la Medicación/estadística & datos numéricos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adulto , Carga Viral/efectos de los fármacos , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Estudios de Cohortes , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéuticoRESUMEN
INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. MATERIALS & METHODS: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. DISCUSSION: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.
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Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Piridonas , Humanos , Femenino , Embarazo , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Piperazinas/efectos adversos , Piperazinas/uso terapéutico , Adulto , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Preescolar , Lactante , Recién Nacido , Obesidad/inducido químicamente , Obesidad/epidemiología , Resistencia a la Insulina , Masculino , Aumento de Peso/efectos de los fármacos , Estudios de Cohortes , Sudáfrica/epidemiologíaRESUMEN
PURPOSE OF REVIEW: To analyze the efficacy and safety of Janus kinase inhibitors (JAKi) in the treatment of pediatric AD. RECENT FINDINGS: Adolescents with moderate and severe atopic dermatitis (AD) need systemic therapies, as stated several recent practice guidelines. (JAKi) have shown their efficacy in the treatment of adult AD, however, there is a lack of information concerning efficacy and safety of their use in pediatric AD. We found that the JAKi's abrocitinib (ABRO), baricitinib (BARI), and upadacitinib (UPA), are all an effective treatment option with a very fast onset of action for adolescents with moderate-to-severe AD. BARI was not effective in children between 2 and 10 years with moderate-to-severe AD. Fortunately, major safety issues with JAKi in adolescents with AD have not been documented in the trials, so far, contrasting with the reports in adults with AD, where these events have very rarely occurred. There are some reports of herpes zoster (HZ) infection in adolescents on JAKi, but it is not a major safety concern. Acne is a relatively common AE with UPA in adolescents; however, it is responsive to standard treatment. This review will help the clinician to choose among the JAKi according to the needs and clinical features of patients with moderate and severe AD. In the following years, with the advent of new biologicals and JAKi, these therapies will fall into place in each phase of the evolution of patients with AD.
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Dermatitis Atópica , Inhibidores de las Cinasas Janus , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Inhibidores de las Cinasas Janus/administración & dosificación , Niño , Adolescente , Purinas/uso terapéutico , Administración Oral , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Resultado del TratamientoAsunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Costos de los Medicamentos , Piridonas/economía , Piridonas/uso terapéutico , Profilaxis Pre-Exposición/economía , Profilaxis Pre-Exposición/métodos , Compuestos Heterocíclicos con 3 Anillos/economía , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Oxazinas/uso terapéutico , PiperazinasRESUMEN
BACKGROUND: There is a need to understand health care resource utilization (HCRU) and costs associated with treatment-experienced people with HIV (PWH) switching treatment regimens. OBJECTIVE: To describe HCRU and cost during lines of antiretroviral therapy (ART) for treatment-experienced PWH switching to or restarting guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multitablet regimens and single-tablet regimens. METHODS: This retrospective claims study used data from Optum Research Database (January 1, 2010, to March 31, 2020) to identify lines of therapy (LOTs) for treatment-experienced adults who switched to or restarted INSTI-based regimens between January 1, 2018, and December 31, 2019. The first LOT during the study period was included in the analysis. We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). Analysis of HCRU by site of service was conducted following inverse probability treatment weighting. Multivariable regression was conducted using a generalized linear model with stepwise covariate selection to estimate HIV-related medical costs and control for remaining differences after inverse probability treatment weighting. RESULTS: 4,251 PWH were identified: B/F/TAF (n = 2,727; 64.2%), DTG/ABC/3TC (n = 898; 21.1%), DTG+FTC/TAF (n = 539; 12.7%), and DTG+FTC/TDF (n = 87; 2.1%). PWH treated with DTG+FTC/TAF had a significantly higher mean of all-cause ambulatory visits than PWH treated with B/F/TAF (1.8 vs 1.6, P < 0.001). A significantly smaller proportion of PWH treated with DTG/ABC/3TC had an all-cause ambulatory visit vs PWH treated with B/F/TAF (90.6% vs 93.9%, P < 0.001). All-cause total costs were not significantly different between regimens. Mean (SD) medical HIV-related costs per month during the LOT were not significantly different between B/F/TAF $699 (3,602), DTG/ABC/3TC $770 (3,469), DTG+FTC/TAF $817 (3,128), and DTG+FTC/TDF $3,570 (17,691). After further controlling for unbalanced measures, HIV-related medical costs during the LOT were higher (20%) but did not reach statistical significance for DTG/ABC/3TC (cost ratio = 1.20, 95% CI = 0.851-1.694; P = 0.299), 49% higher for DTG+FTC/TAF (cost ratio = 1.489, 95% CI = 1.018-2.179; P = 0.040), and almost 11 times greater for DTG+FTC/TDF (cost ratio = 10.759, 95% CI = 2.182-53.048; P = 0.004) compared with B/F/TAF. CONCLUSIONS: HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs.
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Fármacos Anti-VIH , Infecciones por VIH , Piridonas , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Piridonas/economía , Piridonas/uso terapéutico , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/economía , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Tenofovir/uso terapéutico , Tenofovir/economía , Aceptación de la Atención de Salud/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Combinación de Medicamentos , Oxazinas/uso terapéutico , Oxazinas/economía , Emtricitabina/uso terapéutico , Emtricitabina/economía , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/economía , Piperazinas/economía , Piperazinas/uso terapéutico , Lamivudine/economía , Lamivudine/uso terapéutico , Inhibidores de Integrasa VIH/economía , Inhibidores de Integrasa VIH/uso terapéutico , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Sustitución de Medicamentos/economía , Amidas , Ciclopropanos , Didesoxiadenosina/análogos & derivadosRESUMEN
INTRODUCTION: Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited. METHODS: Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30 mg, VEDO 300 mg intravenously every 8 weeks (Q8W), UST 90 mg SC Q8W, or oral TOFA 5 mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator. RESULTS: The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15 mg versus VEDO and TOFA (p < 0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30 mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators. CONCLUSION: In patients with active UC, greater clinical efficacy, and similar safety after 1 year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.
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Anticuerpos Monoclonales Humanizados , Colitis Ulcerosa , Compuestos Heterocíclicos con 3 Anillos , Piperidinas , Pirimidinas , Ustekinumab , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Femenino , Adulto , Persona de Mediana Edad , Ustekinumab/uso terapéutico , Resultado del Tratamiento , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Pirroles/uso terapéutico , Pirroles/efectos adversos , Pirroles/administración & dosificación , Quimioterapia de Mantención/métodosRESUMEN
Introduction: VESTED (NCT03048422) compared the safety and efficacy of three antiretroviral treatment (ART) regimens in pregnant and postpartum women: dolutegravir+emtricitabine/tenofovir alafenamide fumarate; dolutegravir+emtricitabine/tenofovir disoproxil fumarate (TDF); efavirenz/emtricitabine/TDF. Vertical HIV transmission (VT) occurred to 4/617 (0.60%) live-born infants, who were evaluated for HIV drug resistance (HIVDR) and other risk factors. Setting: In 2018-2020, pregnant (weeks-14-28) women living with HIV and ≤14 days of ART were enrolled at 22 international sites and followed with their infants through 50 weeks postpartum. Methods: HIV sequences derived by single genome amplification (SGA) from longitudinally collected specimens were assessed from VT Cases for HIVDR in protease, reverse transcriptase, integrase, and the nef 3'polypurine tract (3'PPT). Results: The four Case mothers were prescribed efavirenz-based-ART for 1-7 days prior to randomization to study ART. Their infants received postnatal nevirapine+/-zidovudine prophylaxis and were breastfed. A total of 833 SGA sequences were derived. The "major" (Stanford HIVDR Score ≥60) non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation (K103N) was detected persistently in one viremic mother, and likely contributed to VT of HIVDR. Major NNRTI HIVDR mutations were detected in all three surviving infants. No integrase, nor high frequencies of 3'PPT mutations conferring dolutegravir HIVDR were detected. The timing of HIV infant diagnosis, plasma HIV RNA levels and HIVDR suggests one in utero, one peripartum, one early, and one late breastfeeding transmission. Conclusions: VT was rare. New-onset NNRTI HIVDR in Case mothers was likely from efavirenz-ART prescribed prior to study dolutegravir-ART, and in one case appeared transmitted to the infant despite nevirapine prophylaxis.
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Fármacos Anti-VIH , Farmacorresistencia Viral , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Farmacorresistencia Viral/genética , Embarazo , Fármacos Anti-VIH/uso terapéutico , Adulto , Recién Nacido , Piperazinas/uso terapéutico , Ciclopropanos , VIH-1/genética , VIH-1/efectos de los fármacos , Tenofovir/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Alquinos , Piridonas/uso terapéutico , Emtricitabina/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/virología , Benzoxazinas/uso terapéutico , Oxazinas/uso terapéuticoRESUMEN
INTRODUCTION: HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the WHO in 2019 for first-line, second-line and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance. METHODS AND ANALYSIS: Nested within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST is a multicentre study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virological failure on dolutegravir-based ART. At the time of virological failure, whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (1) individuals who experienced virological failure on dolutegravir and (2) those who started or switched to such a regimen and were at risk of virological failure. For population (1), the outcome will be any InSTI drug resistance mutations, and for population (2) virological failure is defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virological failure and limited power for analysing factors associated with individual InSTI drug resistance mutations. ETHICS AND DISSEMINATION: The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in International epidemiology Databases to Evaluate AIDS and have obtained ethics approval from their local ethics committee to collect additional data. TRIAL REGISTRATION NUMBER: NCT06285110.
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Farmacorresistencia Viral , Infecciones por VIH , Inhibidores de Integrasa VIH , VIH-1 , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piperazinas , Piridonas , Humanos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Oxazinas/uso terapéutico , VIH-1/genética , VIH-1/efectos de los fármacos , Piperazinas/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/epidemiología , Farmacorresistencia Viral/genética , Inhibidores de Integrasa VIH/uso terapéutico , Adulto , Adolescente , Estudios Multicéntricos como Asunto , Carga Viral , Genotipo , Femenino , Masculino , África del Sur del Sahara/epidemiologíaRESUMEN
We describe and analyze resistance-associated mutations (RM) and virological failures (VF) on antiretroviral therapy using the latest approved integrase inhibitors (INIs) dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB), together with their companion drugs in fixed-dose formulations: BIC/emtricitabine/tenofovir; CAB/rilpivirine; DTG/abacavir/lamivudine; DTG/emtricitabine/tenofovir; and DTG/lamivudine. Systematic literature searches were conducted in PubMed and other electronic databases for clinical studies published between January 2010 and May 2023, according to preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA), which analyzed VFs and RMs of INIs. Fifty clinical studies were included in the synthesis. VF in antiretroviral treatment (ART)-naïve patients occurred in 0.7-4.0%, 0.6-1.4%, and 0.6-9.0% of patients treated with DTG, BIC, and CAB, respectively. VF was reported in patients with previous ART in 0-8.1%, 0-2.0%, and 0.4-2.3% of those treated with DTG, BIC, and CAB, respectively. RMs were detected in ART-naïve patients in only one study with DTG (0.3%), none of the studies with BIC, and three of the studies with CAB (0.1-5.4%). In ART-experienced patients, RMs were detected in 0-1.9% of DTG-treated patients. No cases of RM were detected in the 11 BIC studies reviewed. In the case of CAB, RMs were detected in eight studies, ranging from 0.3% to 1.9% of patients. In conclusion, RM rates in the studies reviewed were generally low using the latest INIs. This review identified BIC as the INI with the lowest number of observed VF and lack of RM.
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Farmacorresistencia Viral , Infecciones por VIH , Inhibidores de Integrasa VIH , VIH-1 , Compuestos Heterocíclicos con 3 Anillos , Compuestos Heterocíclicos de 4 o más Anillos , Oxazinas , Piperazinas , Piridonas , Humanos , Piridonas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Piridazinas/uso terapéutico , Piridazinas/farmacología , Insuficiencia del Tratamiento , Amidas/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , DicetopiperazinasRESUMEN
OBJECTIVES.: To analyze the budget impact of upadacitinib (UPA) 15 mg + methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients with an inadequate response to conventional disease-modifying antirheumatic drugs (cDMARD-IR) from the perspective of social security and the private health sector in Argentina. MATERIALS AND METHODS.: A budget impact analysis model was developed for a hypothetical cohort of 100,000 adults with health insurance coverage who were diagnosed with RA over a 5-year time horizon. The model parameters were obtained through literature review and validated by local experts. The costs are expressed in 2024 US dollars (USD). RESULTS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR resulted in minimal increase, with a five-year total cumulative incremental cost of USD 1,855 for social security and USD 1,812 for the private health sector, representing 2% of the total budget. The acquisition cost of UPA was the most influential variable in the sensitivity analysis. CONCLUSIONS.: The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR can provide an effective treatment option with a minimal increase in costs for the healthcare system in Argentina, which is especially important in developing countries where health system budgets are more limited. Providing evidence-based estimates is a valuable tool for informing healthcare policies and can help policymakers make informed decisions about the allocation of healthcare resources to improve patient outcomes while also managing costs.Motivation for the study. Rheumatoid arthritis (RA) is a disease that hasn't cure, so it's important to know the budget impact of treatment with upadacitinib (UPA) 15 mg + methotrexate (MTX) in patients with moderate to severe RA who didn't respond well to conventional antirheumatic drugs. Main findings. UPA + MTX would entail a minimal increase in costs for the healthcare system in Argentina, potentially making this effective treatment option more accessible to patients with RA. Access to this treatment can improve the outcome of patients with RA. Public health implications. In resource-constrained settings such as Argentina, providing evidence-based cost estimates can help healthcare managers allocate resources efficiently while improving patient outcomes. This study provides evidence to inform healthcare policies and decisions regarding the inclusion of UPA + MTX in treatment guidelines or formularies for RA management.
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Antirreumáticos , Artritis Reumatoide , Presupuestos , Compuestos Heterocíclicos con 3 Anillos , Metotrexato , Argentina , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/economía , Antirreumáticos/economía , Antirreumáticos/uso terapéutico , Metotrexato/economía , Metotrexato/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/economía , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Índice de Severidad de la Enfermedad , Quimioterapia CombinadaRESUMEN
Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa.