RESUMO
Distal sensory polyneuropathy (DSP) is the most common neurological problem in HIV/AIDS Patients. It represents a complex symptom that occurs because of peripheral nerve damage related to advanced HIV disease and in association with the use of antiretroviral therapy. DSP is a frequent symptom in which the specific pathophysiology is not well understood. Recently, mitochondrial toxicity and antiretroviral toxic neuropathies have been more identified as a possible etiology of DSP. This study's objective was to determine factors associated with DSP severity in HIV/AIDS patients. This cross-sectional study was followed by 50 HIV/AIDS outpatients at some hospitals in Makassar, Indonesia who met the inclusion criteria. DSP is diagnosed using non-invasive screening tools subjective peripheral neuropathy screen (SPNS) which can determine the severity of DSP in advance. Some factors were analyzed by using Pearson's chi-square test and Spearman's correlation test. Forty-three participants (86%) had diagnosed DSP which is mostly moderate in severity (48%). Statistical analysis showed significant correlation between HIV/AIDS Stage and DSP severity (p=0.032) meanwhile CD4 count, antiretroviral, body mass index (BMI), and hemoglobin level have no significant correlation to DSP severity. In conclusion, HIV/AIDS stage and DSP severity correlate where the later the stage the more severe DSP.
Assuntos
Infecções por HIV , Polineuropatias , Índice de Gravidade de Doença , Humanos , Estudos Transversais , Masculino , Indonésia/epidemiologia , Feminino , Polineuropatias/etiologia , Polineuropatias/diagnóstico , Polineuropatias/epidemiologia , Polineuropatias/fisiopatologia , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Pessoa de Meia-Idade , Contagem de Linfócito CD4 , Adulto Jovem , Síndrome da Imunodeficiência Adquirida/complicações , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Índice de Massa CorporalRESUMO
INTRODUCTION: Among many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta-analysis evaluates the relationship between tenofovir alafenamide use and lipid-profile alterations in people living with HIV. METHODS: We searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated. RESULTS: Sixty-five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low-density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low-density lipoprotein cholesterol (-9.31 mg/dl) and total cholesterol (-8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92-1.84), which became more pronounced over time. Meta-regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide. CONCLUSIONS: Tenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.
Assuntos
Fármacos Anti-HIV , Dislipidemias , Infecções por HIV , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Dislipidemias/induzido quimicamente , Alanina/uso terapêutico , Fatores de Risco , Masculino , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Feminino , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversosRESUMO
BACKGROUND: Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia. METHOD: PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia. RESULT: The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28-3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50-3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10-3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF. CONCLUSION: The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease.
Assuntos
Terapia Antirretroviral de Alta Atividade , Benzoxazinas , Dislipidemias , Infecções por HIV , Lamivudina , Humanos , Dislipidemias/epidemiologia , Dislipidemias/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Masculino , Feminino , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Pessoa de Meia-Idade , China/epidemiologia , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Benzoxazinas/administração & dosagem , Lamivudina/uso terapêutico , Lamivudina/efeitos adversos , Ciclopropanos , Alcinos , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Zidovudina/efeitos adversos , Zidovudina/uso terapêutico , Fatores de Risco , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , PrevalênciaRESUMO
Side effects are a common concern of current and potential HIV pre-exposure prophylaxis (PrEP) users, potentially leading to missed doses. We examined the relationship between reported side effects and adherence in the Ontario PrEP Cohort Study (ON-PrEP). In total, 600 predominantly gay (87.3%), White (65.8%), and male (95.0%) participants completed questionnaires assessing the presence and severity of five side effect categories (nausea, diarrhea, headache, abdominal pain, and "other") as well as their adherence to daily PrEP (any missed doses in the previous 4 days). In total, 175 participants (29%) ever reported experiencing side effects: most commonly diarrhea (7.5% of study visits), and most were of mild severity. Lower incomes (p = 0.01), identifying as bisexual (p = 0.04), and baseline concern about side effects (p < 0.001) were associated with ever reporting side effects. The odds of reporting any side effects decreased by a factor of 0.44 (95% confidence interval 0.25-0.80) with each additional year of PrEP use, however 1 in 10 participants still reported side effects after 1 year of use. The odds of reporting optimal adherence were 0.48 (0.28-0.83) times lower for participants reporting any side effects, 0.67 (0.51-0.89) times lower per additional side effect category reported, and 0.78 (0.65-0.97) times lower per incremental increase in side effect severity ratings. We found some evidence of interaction between side effect measures and duration of PrEP use, suggesting that these relationships were stronger for participants taking PrEP for longer. Clinicians should make efforts to ascertain patients' experience of side effects and consider risk counseling and alternative PrEP regimens to promote adherence.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Profilaxia Pré-Exposição , Humanos , Profilaxia Pré-Exposição/estatística & dados numéricos , Masculino , Infecções por HIV/prevenção & controle , Ontário/epidemiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Feminino , Adesão à Medicação/estatística & dados numéricos , Estudos de Coortes , Pessoa de Meia-Idade , Inquéritos e Questionários , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
Purpose: People living with HIV are twice as likely to develop cardiovascular diseases (CVDs) and myocardial infarction related to atherosclerosis than the uninfected population. This study aimed to evaluate the prevalence of subclinical atherosclerosis in a young, mid-eastern European population of PLWH receiving ART for undetectable viremia. Patients and Methods: This was a single-centre study. We included 34 patients below 50 years old, treated in Szczecin, Poland, with confirmed HIV-1 infection, treated with antiretroviral therapy (ART), and undetectable viremia. All patients underwent coronary artery computed tomography (CACT), carotid artery intima-media thickness (IMT) evaluation, and echocardiography. Results: In the primary assessment, only two (5.8%) patients had an increased CVD risk calculated using the Framingham Risk Score (FRS), but we identified coronary or carotid plaques in 26.5% of the patients. Neither traditional risk factors nor those associated with HIV significantly influenced the presence of the plaque. IMT was significantly positively correlated with age and the FRS (R=0.38, p=0.04). Relative wall thickness assessed in echocardiography was higher in those with plaque (0.49 vs 0.44, p=0.04) and significantly correlated with IMT (R=0.38, p=0.04). Conclusion: In our population, more than a quarter of PLWH with undetectable viremia had subclinical atherosclerosis in either the coronary or carotid arteries. The FRS underpredicted atherosclerosis in this population. The role of RWT as a possible early marker of atherosclerosis needs further studies.
Assuntos
Fármacos Anti-HIV , Espessura Intima-Media Carotídea , Infecções por HIV , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/complicações , Feminino , Pessoa de Meia-Idade , Adulto , Polônia/epidemiologia , Prevalência , Medição de Risco , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Dados Preliminares , Viremia/epidemiologia , Viremia/tratamento farmacológico , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Resultado do Tratamento , Placa Aterosclerótica , Angiografia por Tomografia Computadorizada , Doenças Assintomáticas , Angiografia Coronária , Fatores Etários , Resposta Viral Sustentada , Carga Viral , Fatores de Risco , Estudos TransversaisRESUMO
BACKGROUND: Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS: A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. RESULTS: Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. CONCLUSIONS: Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.
Assuntos
Fármacos Anti-HIV , Densidade Óssea , Infecções por HIV , Período Pós-Parto , Humanos , Feminino , Gravidez , Adulto , Densidade Óssea/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Absorciometria de Fóton , Adulto Jovem , Biomarcadores/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Creatinina/sangueRESUMO
BACKGROUND: Peripheral neuropathy (PN) is a common neurological complication of HIV (Human Immunodeficiency Virus) that can significantly affect patients' quality of life. In Ethiopia, children living with HIV are at an increased risk of developing peripheral neuropathy due to comorbidities such as anemia, tuberculosis, malnutrition, and poor socio-economic status. Our study aims to evaluate the prevalence of peripheral neuropathy among children living with HIV in Ethiopia using a simple clinical screening tool. METHODS: A health institution-based cross-sectional study was conducted among 148 children aged 5 to 18 years living with HIV who are receiving treatment at the antiretroviral therapy (ART) clinic of the randomly selected public health institutions in the Gamo zone. An interview and neurologic examination were conducted. A binary logistic regression model was used to identify factors associated with the outcome variable. Variables with p-value < 0.25 in the bi-variable logistic regression analysis were entered and checked for association in a multivariable logistic regression model. The level of statistical significance was declared at the p-value < 0.05. RESULT: In this study, 148 children participated, making a response rate of 97.5%. The mean ± standard deviation (SD) age of the respondents was 15.03 ± 2.99 years, and 81(54.7%) were male. The magnitude of PN was 20.9% (31/148). Children in the age category of 15-18 (adjusted odds ratio (AOR) = 1.88, 95%CI; 1.24-4.60), low BMI for age (AOR = 1.66, 95%CI; 1.12-4.15), last exposure to isoniazid within 1 year (AOR = 2.31, 95%CI; 1.12-8.53). Longer duration of HIV illness (AOR = 2.17, 95%CI; 1.54-4.64), and past tuberculosis (TB) treatment (AOR = 2.11, 95%CI; 1.08-7.48) were significantly associated factors with peripheral neuropathy. CONCLUSION: Our analysis revealed that being in the age category of 15-18 years, low BMI for age, Isoniazid exposure, longer Duration of HIV illness, and past TB treatment were significantly associated with peripheral neuropathy in children living with HIV. These disease-related factors may contribute to the development and progression of peripheral neuropathy in this population. CLINICAL TRIAL NUMBER: Not applicable.
Assuntos
Infecções por HIV , Doenças do Sistema Nervoso Periférico , Humanos , Etiópia/epidemiologia , Estudos Transversais , Masculino , Feminino , Adolescente , Criança , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Pré-Escolar , Prevalência , Fatores de Risco , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversosRESUMO
PURPOSE: Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. METHODS: This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. RESULTS: Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. CONCLUSION: This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.
Assuntos
Fármacos Anti-HIV , Didanosina , Infecções por HIV , Doenças Retinianas , Humanos , Didanosina/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Prevalência , Idoso , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/diagnóstico , Doenças Retinianas/epidemiologia , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Adulto , Fatores de Risco , Centros Médicos Acadêmicos , Retina/efeitos dos fármacos , Retina/diagnóstico por imagem , Retina/patologia , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: The pathogenesis of HIV-associated neurocognitive (NC) impairment is multifactorial, and antiretroviral (ARV) neurotoxicity may contribute. However, interventional pharmacological studies are limited. METHODS: Single-blind, randomized (1:1), controlled trial to assess the change of NC performance (Global Deficit Score, GDS, and domain scores) in PLWH with NC impairment randomized to continue their standard of care treatment or to switch to a less neurotoxic ARV regimen: darunavir/cobicistat, maraviroc, emtricitabine (MARAND-X). Participants had plasma and cerebrospinal fluid HIV RNA< 50 copies/mL, R5-tropic HIV, and were on ARV regimens that did not include efavirenz and darunavir. The change of resting-state electroencephalography was also evaluated. The outcomes were assessed at week 24 of the intervention through tests for longitudinal paired data and mixed-effect models. RESULTS: Thirty-eight participants were enrolled and 28 completed the follow-up. Global Deficit Score improved over time but with no difference between arms in longitudinal adjusted models. Perceptual functions improved in the MARAND-X, while long-term memory improved only in participants within the MARAND-X for whom the central nervous system penetration-effectiveness (CNS penetration effectiveness) score increased by ≥3. No significant changes in resting-state electroencephalography were observed. CONCLUSIONS: In this small but well-controlled study, the use of less neurotoxic ARV showed no major beneficial effect over an unchanged regimen. The beneficial effects on the memory domain of increasing CNS penetration effectiveness score suggest that ARV neuropenetration may have a role in cognitive function.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Emtricitabina/uso terapêutico , Método Simples-Cego , HIV-1 , Complexo AIDS Demência/tratamento farmacológico , Maraviroc/uso terapêutico , Darunavir/uso terapêutico , Cobicistat/uso terapêutico , Transtornos Neurocognitivos/tratamento farmacológico , Transtornos Neurocognitivos/etiologia , Eletroencefalografia , Cognição/efeitos dos fármacosRESUMO
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.
Assuntos
Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Transmissão Vertical de Doenças Infecciosas , Oxazinas , Piperazinas , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Piridonas , Humanos , Gravidez , Feminino , Etiópia/epidemiologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Estudos Retrospectivos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto Jovem , Ciclopropanos , Benzoxazinas/uso terapêutico , Benzoxazinas/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Alcinos , Estudos de Coortes , Nascimento Prematuro/epidemiologiaRESUMO
INTRODUCTION: The course of HIV infection has changed radically with the introduction of antiretroviral therapy (ART), which has significantly reduced mortality and improved quality of life. However, antiretroviral drugs can cause adverse effects, including cardiometabolic complications and diseases, which are among the most common. Compared to the adult population, there are fewer studies in the pediatric population on treatment-related complications. The purpose of this review is to provide an update on the literature regarding cardiometabolic complications and diseases in children and adolescents with HIV. AREAS COVERED: A comprehensive literature review was conducted using PubMed and related bibliographies to provide an overview of the current knowledge of metabolic complications (dyslipidemia, insulin resistance, lipodystrophy, weight gain and liver complications) and diseases (prediabetes/diabetes and cardiovascular diseases) associated with ART in children and adolescents with HIV. EXPERT OPINION: Metabolic complications are conditions that need to be closely monitored in children and adolescents with HIV, as they increase the risk of early development of non-communicable diseases, such as cardiovascular disease. Key areas for improvement include ensuring access to treatment, reducing side effects and improving diagnostic capabilities. Overcoming existing challenges will require collaborative efforts across disciplines, advances in technology, and targeted interventions to address socioeconomic disparities.
Assuntos
Fármacos Anti-HIV , Doenças Cardiovasculares , Infecções por HIV , Doenças Metabólicas , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Criança , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Adolescente , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/epidemiologia , Qualidade de VidaRESUMO
OBJECTIVES: Tuberculosis (TB) risk after initiation of antiretroviral treatment (ART) is not well described in a European setting, with an average TB incidence of 25/105 in the background population. METHODS: We included all adult persons with HIV starting ART in the RESPOND cohort between 2012 and 2020. TB incidence rates (IR) were assessed for consecutive time intervals post-ART initiation. Risk factors for TB within 6 months from ART initiation were evaluated using Poisson regression models. RESULTS: Among 8441 persons with HIV, who started ART, 66 developed TB during 34,239 person-years of follow-up (PYFU), corresponding to 1.87/1000 PYFU (95% confidence interval [CI]: 1.47-2.37). TB IR was highest in the first 3 months after ART initiation (14.41/1000 PY (95%CI 10.08-20.61]) and declined at 3-6, 6-12, and >12 months post-ART initiation (5.89 [95%CI 3.35-10.37], 2.54 [95%CI 1.36-4.73] and 0.51 [95%CI 0.30-0.86]), respectively. Independent risk factors for TB within the first 6 months after ART initiation included follow-up in Northern or Eastern Europe region, African origin, baseline CD4 count <200 cells/mm3, HIV RNA >100,000 copies/mL, injecting drug use and heterosexual transmission. CONCLUSIONS: TB IR was highest in the first 3 months post-ART initiation and was associated with baseline risk factors, highlighting the importance of thorough TB risk assessment at ART initiation.
Assuntos
Infecções por HIV , Tuberculose , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Masculino , Feminino , Adulto , Fatores de Risco , Tuberculose/epidemiologia , Europa (Continente)/epidemiologia , Incidência , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos de CoortesRESUMO
BACKGROUND: Tenofovir-containing antiretroviral therapy regimens may have long-term toxicity-related side effects. This study aimed to compare the virological efficacy of co-formulated darunavir/ritonavir plus lamivudine with darunavir/ritonavir plus tenofovir and emtricitabine or lamivudine. METHODS: The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in treatment-naïve adults living with human immunodeficiency virus (HIV). Patients were randomized on a 1:1 basis to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir/ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir/ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of <50 copies/mL at week 48 in the intention-to-treat population. The US Food and Drug Administration snapshot algorithm and a non-inferiority margin of -12% were used. The secondary objective was to analyse safety in the per-protocol population. This study has been registered at ClinicalTrials.gov (NCT02770508). RESULTS: Between November 2015 and 31 October 2020, 336 participants were assigned at random to the triple therapy arm (n=165) or the dual therapy arm (n=171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the dual therapy group (91%) achieved virological suppression (difference -2.1%, 95% confidence interval -7.0 to 2.9). Drug-related adverse events were more common in the triple therapy group (P=0.04). Two toxicity-related events led to discontinuation in each group. INTERPRETATION: Co-formulated darunavir/ritonavir plus lamivudine showed non-inferiority and a safer toxicity profile compared with the standard-of-care triple therapy regimen including tenofovir in treatment-naïve patients.
Assuntos
Fármacos Anti-HIV , Darunavir , Quimioterapia Combinada , Infecções por HIV , Lamivudina , Ritonavir , Carga Viral , Humanos , Infecções por HIV/tratamento farmacológico , Darunavir/uso terapêutico , Darunavir/administração & dosagem , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Ritonavir/uso terapêutico , Ritonavir/administração & dosagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carga Viral/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Tenofovir/uso terapêutico , Tenofovir/administração & dosagem , HIV-1/efeitos dos fármacos , Combinação de Medicamentos , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Echocardiography can be used to screen, confirm, and assist in the management of some cardiovascular diseases in people living with human immunodeficiency virus (HIV) (PLWH). Thus, complications from subclinical cardiovascular conditions or more apparent conditions, such as massive pericardial effusion with tamponade, can be promptly identified and managed to minimize cardiovascular morbidity and mortality associated with HIV infection. Since the introduction of antiretroviral therapy (ART) in Ghana approximately two decades ago, studies on the prevalence and patterns of echocardiographic abnormalities among PLWH on ART have been limited. This study was designed to assess the prevalence and patterns of echocardiographic abnormalities among PLWH on ART. METHODS: This was a cross-sectional study. PLWH on ART (cases) attending the HIV clinic at Komfo Anokye Teaching Hospital (KATH) and HIV-negative blood donors (controls) were consecutively recruited and enrolled in this study. The interviews were performed via a standardized questionnaire. After a clinical examination was performed, all patients underwent two-dimensional (2D) and Doppler transthoracic echocardiograms. The prevalence and patterns of echocardiographic abnormalities were characterized. RESULTS: There were 117 patients in each arm of the study. There were more females than males among both the cases (92 (78.6%) and controls (80 (68.4%)); however, the sex distribution was similar between the two groups (p = 0.075). For clinical characteristics such as age, weight, height and blood pressure, there were no statistically significant differences between the cases and controls. Echocardiographic abnormalities were more frequently observed and demonstrated a statistically significant difference between cases and controls, with an overall prevalence of 35.0% among cases and 19.7% among controls (p = 0.008). The echocardiographic abnormalities that demonstrated significant differences between the cases and controls were left ventricular (LV) diastolic dysfunction (28.2% versus 8.6%; p = 0.000) and LV hypertrophy (7% versus 0.9%; p = 0.017). CONCLUSION: Nearly 1 in 3 PLWH on ART had an echocardiographic abnormality in this Ghanaian study. Echocardiograms are recommended as helpful screening modalities for diagnosing cardiac abnormalities among PLWH on ART.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Gana/epidemiologia , Feminino , Masculino , Estudos Transversais , Prevalência , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Adulto , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Valor Preditivo dos Testes , Ecocardiografia Doppler , Estudos de Casos e Controles , Cardiopatias/epidemiologia , Cardiopatias/diagnóstico por imagem , Adulto Jovem , Função Ventricular Esquerda/efeitos dos fármacos , Resultado do TratamentoRESUMO
The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies.
Assuntos
Neuralgia , Inibidores da Transcriptase Reversa , Animais , Neuralgia/tratamento farmacológico , Neuralgia/induzido quimicamente , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/farmacologia , Camundongos , Masculino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/efeitos adversos , Modelos Animais de Doenças , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Camundongos Endogâmicos C57BLRESUMO
PURPOSE OF REVIEW: This review examines the impact of HIV on kidney disease, which remains significant despite advances in antiretroviral therapy (ART). The review is timely due to the shifting epidemiology of kidney disease in people with HIV (PWH), driven by increased ART access, noncommunicable diseases, and region-specific opportunistic infections like tuberculosis. RECENT FINDINGS: The literature highlights a decline in HIV-associated nephropathy (HIVAN) and a rise in tubulointerstitial diseases and noncommunicable diseases among PWH. Studies from the United States and South Africa report decreased HIVAN prevalence and increased rates of tubulointerstitial diseases linked to tenofovir disoproxil fumarate (TDF) toxicity and tuberculosis (TB). Immune complex glomerulonephritis (ICGN) and diabetic kidney disease (DKD) are also prevalent. SUMMARY: The findings underscore the need for improved diagnostic tools for opportunistic infections, management of ART-related complications, and strategies to address noncommunicable diseases in PWH. There is a need to centralize care to address all health needs simultaneously. Future research should focus on APOL1-targeted therapies and the role of SGLT2 inhibitors in CKD. Enhanced transplantation outcomes and the development of guidelines for managing DKD in PWH are critical for advancing clinical practice and improving patient outcomes.
Assuntos
Nefropatia Associada a AIDS , Humanos , Nefropatia Associada a AIDS/epidemiologia , Nefropatia Associada a AIDS/diagnóstico , Nefropatia Associada a AIDS/terapia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). METHODS: This observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. RESULTS: A total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. CONCLUSION: People with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.
Assuntos
Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Tuberculose , Carga Viral , Humanos , Síndrome Inflamatória da Reconstituição Imune/epidemiologia , Masculino , Adulto , Feminino , Incidência , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Contagem de Linfócito CD4 , Tuberculose/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Índia/epidemiologia , Pessoa de Meia-Idade , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológicoRESUMO
This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.