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Journal of the International AIDS... Apr 2024Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and...
INTRODUCTION
Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV.
METHODS
We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula.
RESULTS
Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16).
CONCLUSIONS
Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings.
Topics: Adult; Infant, Newborn; Humans; Male; Female; Middle Aged; Cross-Sectional Studies; Developing Countries; Diabetes Mellitus, Type 2; Overweight; HIV Infections; Liver Cirrhosis; Obesity; Dyslipidemias
PubMed: 38566493
DOI: 10.1002/jia2.26238 -
Radiology. Cardiothoracic Imaging Apr 2024Purpose To assess early subclinical coronary artery disease (CAD) burden and its relation to myocardial function in asymptomatic persons living with HIV (PLWH) who are...
Purpose To assess early subclinical coronary artery disease (CAD) burden and its relation to myocardial function in asymptomatic persons living with HIV (PLWH) who are at low risk for cardiovascular disease (CVD). Materials and Methods In this prospective, HIPAA-compliant study (ClinicalTrials.gov NCT01656564 and NCT01399385) conducted from April 2010 to May 2013, 74 adult PLWH without known CVD and 25 matched healthy controls underwent coronary MRI to measure coronary vessel wall thickness (VWT) and echocardiography to assess left ventricular function. Univariable and multivariable linear regression analyses were used to evaluate statistical associations. Results For PLWH, the mean age was 49 years ± 11 (SD), and the median Framingham risk score was 3.2 (IQR, 0.5-6.6); for matched healthy controls, the mean age was 46 years ± 8 and Framingham risk score was 2.3 (IQR, 0.6-6.1). PLWH demonstrated significantly greater coronary artery VWT than did controls (1.47 mm ± 0.22 vs 1.34 mm ± 0.18; = .006) and a higher left ventricular mass index (LVMI) (77 ± 16 vs 70 ± 13; = .04). Compared with controls, PLWH showed altered association between coronary artery VWT and both E/A (ratio of left ventricular-filling peak blood flow velocity in early diastole [E wave] to that in late diastole [A wave]) ( = .03) and LVMI ( = .04). In the PLWH subgroup analysis, coronary artery VWT increase was associated with lower E/A ( < .001) and higher LVMI ( = .03), indicating restricted diastolic function. In addition, didanosine exposure was associated with increased coronary artery VWT and decreased E/A ratio. Conclusion Asymptomatic low-CVD-risk PLWH demonstrated increased coronary artery VWT in association with impaired diastolic function, which may be amenable to follow-up studies of coronary pathogenesis to identify potential effects on the myocardium and risk modification strategies. Coronary Vessel Wall Thickness, Diastolic Function, HIV, MRI, Echocardiography, Atherosclerosis Clinical trial registration nos. NCT01656564 and NCT01399385 © RSNA, 2024.
Topics: Adult; Humans; Middle Aged; Cardiovascular Diseases; Diastole; Heart; HIV Infections; Prospective Studies
PubMed: 38573125
DOI: 10.1148/ryct.230102 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2020The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production...
The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds.
The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, ., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto's molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT < 4.0 MPa. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.
PubMed: 32194332
DOI: 10.1016/j.jsps.2020.01.010 -
Frontiers in Neurology 2021We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal...
Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature.
We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients. First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms "HIV," "AIDS," "ritonavir," "didanosine," "maculopathy," "retinopathy," "visual loss," and "toxicity" to retrieve the appropriate literature on the subject. Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treatment. Patient 2: A 55-year-old man complained of slowly progressive peripheral visual field constriction for the past 5 years. History disclosed didanosine therapy for 13 years, however, stopped 4 years before the onset of visual symptoms. No alteration of therapy was offered to patient 2 as didanosine therapy was interrupted 9 years previously. Since 2011, 11 cases of ritonavir maculopathy have been reported in the literature. Relentless worsening of vision was reported in 3/7 patients despite cessation of ritonavir therapy. Didonasine peripheral retinopathy was first described in 1992, and a total of 24 patients have been reported since. Relentlessly progressive peripheral retinopathy was diagnosed despite the previous cessation of therapy in 14 patients. Ritonavir causes a slowly progressive atrophic maculopathy, and didanosine toxicity results in a relentlessly progressing peripheral atrophic retinopathy. The relentless progression of both toxic retinopathies reflects permanent alterations of the retinal metabolism by these medications. Both ritonavir and didanosine toxic retinopathies are rare events, but their clinical presentation is highly specific.
PubMed: 34220672
DOI: 10.3389/fneur.2021.663297 -
Cureus Mar 2023Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an...
Noncirrhotic portal hypertension (NCPH) has recently been found in human immunodeficiency virus (HIV)-infected patients taking didanosine. Here, we describe an HIV-infected patient with portal hypertension due to hepatoportal sclerosis who presented with hematemesis at the emergency department (ED). CT angiography of the abdomen and pelvis with and without contrast revealed a diminutive portal vein with corresponding massive lower esophageal varices and superior mesenteric vein to the right gonadal vein varices. Esophagogastroduodenoscopy (EGD) revealed grade II varices were found in the lower third of the esophagus, for which the patient's symptoms improved with emergency endoscopic band ligation, octreotide and didanosine discontinuation. Our case demonstrates a rare complication that can occur with continued didanosine use in an HIV-positive patient. We highlight the need for a standard diagnostic upper gastrointestinal endoscopy to screen for portal hypertension and high-risk esophageal varices in patients with long-term didanosine use as seen in our patient.
PubMed: 37082489
DOI: 10.7759/cureus.36364 -
Pharmaceutics Apr 2021Fluoroquinolones (FQs) are a widespread class of broad-spectrum antibiotics prescribed as a first line of defense, and, in some cases, as the only treatment against...
Fluoroquinolones (FQs) are a widespread class of broad-spectrum antibiotics prescribed as a first line of defense, and, in some cases, as the only treatment against bacterial infection. However, when administered orally, reduced absorption and bioavailability can occur due to chelation in the gastrointestinal tract (GIT) with multivalent metal cations acquired from diet, coadministered compounds (sucralfate, didanosine), or drug formulation. Predicting the extent to which this interaction reduces in vivo antibiotic absorption and systemic exposure remains desirable yet challenging. In this study, we focus on quinolone interactions with magnesium, calcium and aluminum as found in dietary supplements, antacids (Maalox) orally administered therapies (sucralfate, didanosine). The effect of FQ-metal complexation on absorption rate was investigated through a combined molecular and pharmacokinetic (PK) modeling study. Quantum mechanical calculations elucidated FQ-metal binding energies, which were leveraged to predict the magnitude of reduced bioavailability via a quantitative structure-property relationship (QSPR). This work will help inform clinical FQ formulation design, alert to possible dietary effects, and shed light on drug-drug interactions resulting from coadministration at an earlier stage in the drug development pipeline.
PubMed: 33919271
DOI: 10.3390/pharmaceutics13050594 -
MSystems Apr 2020As of today (7 April 2020), more than 81,000 people around the world have died from the coronavirus disease 19 (COVID-19) pandemic. There is no approved drug or vaccine...
As of today (7 April 2020), more than 81,000 people around the world have died from the coronavirus disease 19 (COVID-19) pandemic. There is no approved drug or vaccine for COVID-19, although more than 10 clinical trials have been launched to test potential drugs. In an urgent response to this pandemic, I developed a bioinformatics pipeline to identify compounds and drug candidates to potentially treat COVID-19. This pipeline is based on publicly available single-cell RNA sequencing (scRNA-seq) data and the drug perturbation database "Library of Integrated Network-Based Cellular Signatures" (LINCS). I developed a ranking score system that prioritizes these drugs or small molecules. The four drugs with the highest total score are didanosine, benzyl-quinazolin-4-yl-amine, camptothecin, and RO-90-7501. In conclusion, I have demonstrated the utility of bioinformatics for identifying drugs than can be repurposed for potentially treating COVID-19 patients.
PubMed: 32291351
DOI: 10.1128/mSystems.00297-20 -
PloS One 2023Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have...
BACKGROUND
Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting.
METHODS
We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir.
RESULTS
There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths.
INTERPRETATION
Nirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.
Topics: Adult; Humans; Aged; Outpatients; COVID-19; COVID-19 Vaccines; Retrospective Studies; Ritonavir; COVID-19 Drug Treatment; Didanosine; Drug-Related Side Effects and Adverse Reactions; Antiviral Agents
PubMed: 37856531
DOI: 10.1371/journal.pone.0293302 -
Medicine Nov 2019To assess the utility of spleen stiffness as a diagnostic tool in individuals with human immunodeficiency virus (HIV) and non-cirrhotic portal hypertension (NCPH).The...
To assess the utility of spleen stiffness as a diagnostic tool in individuals with human immunodeficiency virus (HIV) and non-cirrhotic portal hypertension (NCPH).The Philips EPIQ7, a new point shearwave elastography (pSWE) technique, was used to assess liver and spleen stiffness in 3 patient groups. Group 1: HIV and NCPH (n = 11); Group 2: HIV with past didanosine (ddI) exposure without known liver disease or NCPH (n = 5); Group 3: HIV without known liver disease or ddI exposure (n = 9).Groups were matched for age, HIV chronicity, and antiretroviral treatment (including cumulative ddI exposure in Groups 1 and 2). Differences in liver and spleen stiffness (in kPa) between groups were analyzed using the Mann-Whiney U test.Liver and spleen stiffness were both significantly higher in NCPH versus ddI-exposed (P = .019 and P = .006) and ddI-unexposed controls (P = .038 and P < .001). Spleen stiffness was more effective than liver stiffness at predicting NCPH, area under receiver operating characteristic (AUROC) 0.812 versus 0.948. Combining the 2 variables improved the diagnostic performance, AUROC 0.961. The optimal cut-off for predicting NCPH using splenic stiffness was 25.4 kPa, with sensitivity 91%, specificity 93%, positive predictive value (PPV) 91%, negative predictive value (NPV) 93%, positive likelihood ratio 12.73, negative likelihood ratio 0.10. Spleen and liver stiffness scores were strongly correlated (P = .0004, 95% confidence interval [CI] 18, 59).Elevated spleen stiffness is observed in HIV with NCPH and can be quantified easily using pSWE with high diagnostic accuracy. Novel strategies such as pSWE for longitudinal monitoring of patients with HIV and NCPH should be considered.
Topics: Cross-Sectional Studies; Elasticity Imaging Techniques; Female; HIV Infections; Humans; Hypertension, Portal; Male; Middle Aged; Prospective Studies; Spleen
PubMed: 31764798
DOI: 10.1097/MD.0000000000017961 -
PloS One 2020Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the...
Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54-61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9-5.9,), being a female (aOR = 2.1; CI95% = 1.1-4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2-4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5-5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1-3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted.
Topics: Aged; Aged, 80 and over; Anti-HIV Agents; Cote d'Ivoire; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Middle Aged; Physical Functional Performance; Postural Balance; Prevalence; Risk Factors; Self Report; Senegal; Standard of Care
PubMed: 33091061
DOI: 10.1371/journal.pone.0240906