-
Annals of Medicine and Surgery (2012) Dec 2023The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to... (Review)
Review
OBJECTIVE
The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to quantify the association between fall risk and various categories of drugs used in ART.
MATERIAL AND METHODS
PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to January 2023. Any observational study or controlled trial that reported on the relationship of at least one antiretroviral drug with falls in PLHIVs was included. Data on the frequency of single fallers, multiple fallers (≥2 falls), and non-fallers were extracted and studied for each drug and drug category. The pooled results were reported as an odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
A total of five observational studies (51 675 participants) were included out of 414 articles obtained through a literature review. Stavudine use was found to be associated with an increased risk of single falls in PLHIVs (OR: 1.69, 95% CI: 1.08-2.66, =0.02). However, efavirenz (OR: 0.82, 95% CI=0.76-0.89, <0.001) and zidovudine (OR: 0.82, 95% CI=0.77-0.92, <0.001) were found protective against the single falls. Didanosine had no significant association with fall risk (OR: 1.23, 95% CI: 0.78-1.93, =0.37). Likewise, protease inhibitors, integrase inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were discovered to have no significant association with fall risk.
CONCLUSION
Most drug categories of ART have no significant association with the risk of falls in PLHIVs. However, certain drugs, such as didanosine and stavudine, which have the inherent effect of causing balance deficits and neuropathy, should be used cautiously.
PubMed: 38098550
DOI: 10.1097/MS9.0000000000001411 -
Journal of Acquired Immune Deficiency... Feb 2022Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study...
BACKGROUND
Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study explores changes in body fat distribution in relation to ARV exposure.
METHODS
We conducted a prospective study of adults with perinatal HIV (n = 70) using dual-energy X-ray absorptiometry and standard anthropometrics. Trunk to limb fat ratio and waist to hip ratio were compared cross-sectionally to 47 matched controls. Furthermore, changes in body composition and ARV exposure were evaluated longitudinally in a subset of 40 PLWH with a median follow-up of 7 years.
RESULTS
Cross-sectional comparisons of PLWH with controls revealed significantly higher waist to hip ratio, trunk to limb fat ratio, HOMA-IR, and triglycerides, whereas BMI did not differ. Among PLWH with longitudinal follow-up, the prevalence of overweight increased from 27.5% to 52.5% and obesity from 12.5% to 25%; waist to hip and trunk to limb fat ratios also increased (P < 0.0001). Changes in waist to hip ratio were positively correlated with longer exposure during follow-up to darunavir (r = 0.36; P = 0.02), whereas increases in trunk to limb fat ratio were positively correlated with longer exposure to stavudine (r = 0.39; P = 0.01) and didanosine (r = 0.39; P = 0.01) but inversely associated with emtricitabine (r = -0.33; P = 0.04). Increases in waist to hip ratio were correlated with increases in triglyceride levels (r = 0.35; P = 0.03).
CONCLUSION
This study presents strong evidence for persistent and worsening central adiposity in young adults with lifelong HIV and extensive ARV exposure. As this cohort ages, continued evaluation of the body composition and metabolic impact of lifelong ARV therapy is warranted to optimize long-term health.
Topics: Absorptiometry, Photon; Antiviral Agents; Body Composition; Body Mass Index; Child, Preschool; Cross-Sectional Studies; HIV Infections; Humans; Obesity; Obesity, Abdominal; Prospective Studies; Young Adult
PubMed: 34693931
DOI: 10.1097/QAI.0000000000002841 -
Cytokine Dec 2020Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We... (Clinical Trial)
Clinical Trial
BACKGROUND
Lipodystrophy is common in HIV-infected patients receiving protease inhibitors (PIs), stavudine, and zidovudine. Adipocytokines may be altered in lipodystrophy. We evaluated risk factors, adipocytokine levels, insulin resistance, and lipid profiles in HIV-infected adolescents with different lipodystrophy types.
METHODS
A cross-sectional study was conducted in 80 perinatally HIV-infected adolescents receiving PI-based highly active antiretroviral therapy for ≥ 6 months. Patients underwent oral glucose tolerance tests and measurements of high-molecular-weight (HMW) adiponectin, leptin, resistin, insulin, and lipids. They were classified into 3 groups based on the clinical findings: no lipodystrophy, isolated lipoatrophy, and any lipohypertrophy (isolated lipohypertrophy or combined type).
RESULTS
Of the 80 patients (median age, 16.7 years), 18 (22.5%) had isolated lipoatrophy, while 8 (10%) had any lipohypertrophy (four with isolated lipohypertrophy, and four with the combined type). In a multivariate analysis, longer exposure to stavudine (OR: 1.03; 95% CI, 1.01-1.06; p = 0.005) and indinavir (OR: 1.03; 95% CI, 1.01-1.06; p = 0.012) were associated with lipoatrophy, while longer exposure to didanosine (OR: 1.04; 95% CI, 1.01-1.08; p = 0.017) and indinavir (OR: 1.10; 95% CI, 1.00-1.21; p = 0.045) were associated with any lipohypertrophy. Leptin levels were highest in the any-lipohypertrophy group and lowest in the isolated-lipoatrophy group (p = 0.013). HMW adiponectin levels were significantly lowest in the any-lipohypertrophy group and highest in the no-lipodystrophy group (p = 0.001). There were no significant differences in the levels of resistin among the three groups (p = 0.234). The prevalence of insulin resistance (p = 0.002) and prediabetes/diabetes (p < 0.001) were significantly highest in the any-lipohypertrophy group. Patients with lipoatrophy and those without lipodystrophy had comparable degrees of insulin resistance (p = 0.292). In multiple linear regression analysis, adjusted for age, sex, and waist-height ratio, HMW adiponectin levels were associated with Matsuda index (β = 0.5; p = 0.003) and quantitative insulin sensitivity check index (QUICKI) (β = 40.1; p = 0.010) and almost significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.054). Leptin and resistin levels were not associated with HOMA-IR, Matsuda index, or QUICKI (all p > 0.05).
CONCLUSIONS
Abnormal glucose metabolism and dysregulation of adipocytokines were common in the HIV-infected adolescents with lipohypertrophy and the combined type. Preventive screening for cardiovascular diseases caused by metabolic alterations should be routinely performed.
Topics: Adipokines; Adolescent; Adult; Blood Glucose; Cross-Sectional Studies; Female; HIV Protease Inhibitors; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Male
PubMed: 32920318
DOI: 10.1016/j.cyto.2020.155145 -
AIDS Research and Human Retroviruses Mar 2020Mitochondrial DNA (mtDNA) haplogroup has been associated with disease risk and longevity. Among persons with HIV (PWH), mtDNA haplogroup has been associated with AIDS... (Observational Study)
Observational Study
Mitochondrial DNA (mtDNA) haplogroup has been associated with disease risk and longevity. Among persons with HIV (PWH), mtDNA haplogroup has been associated with AIDS progression, neuropathy, cognitive impairment, and gait speed decline. We sought to determine whether haplogroup is associated with frailty and its components among older PWH. A cross-sectional analysis was performed of AIDS Clinical Trials Group A5322 (HAILO) participants with available genome-wide genotype and frailty assessments. Multivariable logistic regression models adjusted for age, gender, education, smoking, hepatitis C, and prior use of didanosine/stavudine. Among 634 participants, 81% were male, 49% non-Hispanic white, 31% non-Hispanic black, and 20% Hispanic. Mean age was 51.0 (standard deviation 7.5) years and median nadir CD4 count was 212 (interquartile range 72, 324) cells/μL; 6% were frail, 7% had slow gait, and 21% weak grip. H haplogroup participants were more likely to be frail/prefrail ( = .064), have slow gait ( = .09), or weak grip ( = .017) compared with non-H haplogroup participants (not all comparisons reached statistical significance). In adjusted analyses, PWH with haplogroup H had a greater odds of being frail versus nonfrail [odds ratio (OR) 4.0 (95% confidence interval 1.0-15.4)] and having weak grip [OR 2.1 (1.1, 4.1)], but not slow gait [OR 1.6 (0.5, 5.0)] compared with non-H haplogroup. Among black and Hispanic participants, haplogroup was not significantly associated with frailty, grip, or gait. Among antiretroviral therapy (ART)-treated PWH, mtDNA haplogroup H was independently associated with weak grip and frailty. This association could represent a mechanism of weakness and frailty in the setting of HIV and ART.
Topics: Adult; Aging; CD4 Lymphocyte Count; Cohort Studies; Cross-Sectional Studies; DNA, Mitochondrial; Female; Frailty; HIV Infections; Haplotypes; Hispanic or Latino; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Factors; Walking Speed
PubMed: 31822125
DOI: 10.1089/AID.2019.0233 -
Analytical Sciences : the International... Jan 2024There is a great concern among the researcher to remove the problem of the persistent organic pollutants in wastewater. Pharmaceutical agrochemical and personal care...
There is a great concern among the researcher to remove the problem of the persistent organic pollutants in wastewater. Pharmaceutical agrochemical and personal care products are generally considered Persistent organic pollutants. Therefore, it is a matter of concern to develop new techniques how to remove these pollutants safely at low cost. This study mainly focuses on the commonly used antiviral drug didanosine and one most commonly used dye rose bengal. In this study, an organic dye rose bengal and TiO nanoparticles have been used in combination with UV light to achieve the photodegradation of selected pharmaceutical products and the dye was also degraded by using TiO Nanoparticles. The formation of three oxidation products was detected by using a very popular separation technique thin layer and column chromatography. The isolated photoproduct was characterized by using advanced characterization techniques like FTIR (Fourier transform infrared spectroscopy), UV Spectroscopy, and Proton and C NMR (Nuclear Magnetic Resonance spectroscopy). The role of singlet oxygen as an active species in this reaction was confirmed by using DO as a reaction medium. The role of singlet oxygen in this photochemical reaction was also established by the addition of sodium azide. The TiO nanophotocatalyst efficiently degrade the didanosine and rose bengal in the presence of the UV light. In the TiO-induced photocatalytic degradation of didanosine and dyes, the hydroxyl and superoxide radical anion play a prominent role. The finding of this manuscript is very useful to develop an efficient low-cost method for the treatment of wastewater contaminated by antiviral drugs, similar pharmaceutical products and dyes. This study was also very helpful to establish a plausible mechanism behind the phototoxicity of the didanosine.
Topics: Rose Bengal; Didanosine; Wastewater; Singlet Oxygen; Persistent Organic Pollutants; Nanoparticles; Superoxides; Coloring Agents; Pharmaceutical Preparations; Antiviral Agents; Titanium; Catalysis
PubMed: 37847356
DOI: 10.1007/s44211-023-00446-x -
The Journal of Infectious Diseases Aug 2021Liver fibrosis is associated with poor liver-related outcomes and mortality. People with human immunodeficiency virus (PWH) may be at increased risk. We aimed to... (Comparative Study)
Comparative Study
BACKGROUND
Liver fibrosis is associated with poor liver-related outcomes and mortality. People with human immunodeficiency virus (PWH) may be at increased risk. We aimed to estimate the prevalence and factors associated with liver fibrosis in PWH compared to population controls.
METHODS
This was a cross-sectional cohort study comparing 342 PWH with 2190 population controls aged 50-70 years.Transient elastography was performed and elevated liver stiffness measurement (LSM) defined as 7.6 kPa as a proxy for significant liver fibrosis. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were computed by logistic regression.
RESULTS
The prevalence of elevated LSM was higher in PWH than in uninfected controls (12% vs 7%; P < .01). Human immunodeficiency virus (HIV) infection was independently associated with elevated LSM. In multivariate analysis, elevated LSM was associated with HIV (aOR, 1.84 [95% CI, 1.17-2.88]; P < .01); higher age (per decade: aOR, 3.34 [95% CI, 1.81-6.18]; P < .01); alanine aminotransferase (ALT) (per 10 IU/L: aOR, 1.25 [95% CI, 1.05-1.49]; P < .01); body mass index (BMI) (per 1 kg/m2: aOR, 1.17 [95% CI, 1.05-1.29]; P < .01), and previous exposure to didanosine (per year: aOR, 2.26 [95% CI, 1.01-5.06]; P = .04).
CONCLUSIONS
The prevalence of elevated LSM was higher in PWH compared to population controls. Higher age, BMI, ALT, previous exposure to didanosine, and positive HIV status were independently associated with higher odds of elevated LSM.
Topics: Aged; Cross-Sectional Studies; Didanosine; Elasticity Imaging Techniques; HIV; HIV Infections; Hepatitis, Viral, Human; Humans; Liver; Liver Cirrhosis; Middle Aged; Population Control; Prevalence
PubMed: 33320268
DOI: 10.1093/infdis/jiaa763 -
Scientific Reports Oct 2019We investigated the effects of treating differentiated retinal pigment epithelial (RPE) cells with didanosine (ddI), which is associated with retinopathy in individuals...
We investigated the effects of treating differentiated retinal pigment epithelial (RPE) cells with didanosine (ddI), which is associated with retinopathy in individuals with HIV/AIDS. We hypothesized that such treatment would cause depletion of mitochondrial DNA and provide insight into the consequences of degradation of RPE mitochondrial function in aging and disease. Treatment of differentiated ARPE-19 or human primary RPE cells with 200 µM ddI for 6-24 days was not cytotoxic but caused up to 60% depletion of mitochondrial DNA, and a similar reduction in mitochondrial membrane potential and NDUFA9 protein abundance. Mitochondrial DNA-depleted RPE cells demonstrated enhanced aerobic glycolysis by extracellular flux analysis, increased AMP kinase activation, reduced mTOR activity, and increased resistance to cell death in response to treatment with the oxidant, sodium iodate. We conclude that ddI-mediated mitochondrial DNA depletion promotes a glycolytic shift in differentiated RPE cells and enhances resistance to oxidative damage. Our use of ddI treatment to induce progressive depletion of mitochondrial DNA in differentiated human RPE cells should be widely applicable for other studies aimed at understanding RPE mitochondrial dysfunction in aging and disease.
Topics: Adenylate Kinase; Cell Differentiation; Cell Line; DNA, Mitochondrial; Didanosine; Epithelial Cells; Glycolysis; Humans; Mechanistic Target of Rapamycin Complex 1; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; Retinal Pigment Epithelium
PubMed: 31653972
DOI: 10.1038/s41598-019-51761-1 -
AIDS Research and Therapy Mar 2022The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the...
BACKGROUND
The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.
METHODS
All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Abdominal and inguinal subcutaneous fat samples were obtained from the HIV+ patients with hemophilia and HIV- healthy volunteers (n = 6 per group), and analyzed via DNA microarray, real-time PCR, flow cytometry and immunohistochemistry.
RESULTS
The time from initial NRTI treatment to collecting samples were 21.7 years in average. Cytometric analysis revealed infiltration of inflammatory M1 macrophages into HIV-infected adipose tissue and depletion of adipose-derived stem cells, possibly due to exhaustion following sustained adipocyte death. Genetic analysis revealed that adipose tissue from HIV+ group had increased immune activation, mitochondrial toxicity, chronic inflammation, progressive fibrosis and adipocyte dysfunction (e.g. insulin resistance, inhibited adipocyte differentiation and accelerated apoptosis). Of note, both triglyceride synthesis and lipolysis were inhibited in adipose tissue from patients with HIV.
CONCLUSIONS
Our findings provide important insights into the pathogenesis of HIV-associated lipodystrophy, suggesting that fat redistribution may critically depend on adipocytes' sensitivity to drug-induced mitochondrial toxicity, which may lead either to atrophy or metabolic complications.
Topics: Anti-HIV Agents; DNA, Mitochondrial; HIV Infections; HIV-Associated Lipodystrophy Syndrome; Hemophilia A; Humans; Lipodystrophy; Subcutaneous Fat
PubMed: 35246167
DOI: 10.1186/s12981-022-00432-9 -
Journal of Vitreoretinal Diseases 2022This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.
PURPOSE
This article describes a case of didanosine (DDI)-associated retinal toxicity in a patient with a heterozygous pathogenic variant in the CRB1 gene.
METHODS
Case report.
RESULTS
A middle-aged patient with HIV controlled on HAART therapy, and a remote 10-year year history of treatment with DDI and tenofivir, presented with external ophthalmoplegia and well-circumscribed, midperipheral patterns of bilateral pigmentary retinopathy and chorioretinal atrophy in both eyes. Genetic testing revealed a heterozygous pathogenic variant in the gene that encodes a protein (Crumbs homolog 1) involved in regulation of cell polarity and junctions and is localized adjacent to mitochondria in the ellipsoid and myoid area.
CONCLUSIONS
This case highlights a potential role for genetic susceptibility to retinal toxicity in DDI-associated retinal toxicity. Large, prospective pharmacogenomics studies may be informative to further elucidate the role of genetic risk factors in drug-induced retinal toxicity.
PubMed: 37007923
DOI: 10.1177/24741264211044599 -
Xenobiotica; the Fate of Foreign... May 2020HIV replication in the brain is unopposed due to reduced antiretroviral drug penetration into the central nervous system (CNS). Prevalence of HIV-associated...
HIV replication in the brain is unopposed due to reduced antiretroviral drug penetration into the central nervous system (CNS). Prevalence of HIV-associated neurocognitive disorder (HAND) has increased severely in patients living with HIV despite current treatments. The aims of this study were to evaluate the brain bio-distribution of alternative nucleoside reverse transcriptase inhibitors, abacavir, stavudine and didanosine in the CNS and to determine their localization patterns in the brain.Sprague-Dawley rats received 50 mg kg single i.p dose of each drug. Mass spectrometric techniques were then used to investigate the pharmacokinetics and localization patterns of these drugs in the brain using LC-MS/MS and mass spectrometric imaging (MSI), respectively.Abacavir, stavudine and didanosine reached the Brain C with concentration of 831.2, 1300 and 43.37 ngmL, respectively. Based on MSI analysis Abacavir and Stavudine were located in brain regions that are strongly implicated in the progression of HAND.Abacavir and Stavudine penetrated into CNS, reaching a C that was above the IC for HIV (457.6 and 112.0 ngmL, respectively), however, it was noted ddI showed poor entry within the brain, therefore, it is recommended that this drug cannot be considered for treating CNS-HIV.
Topics: Animals; Brain; Didanosine; Dideoxynucleosides; HIV Infections; Rats; Reverse Transcriptase Inhibitors; Stavudine; Tandem Mass Spectrometry
PubMed: 31403353
DOI: 10.1080/00498254.2019.1655605