APOC3 Gene Polymorphism and Antiretroviral Therapy-Induced Dyslipidemia in HIV-Infected Children.
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ABSTRACT:
SUBMITTER: Srinivasan R
PROVIDER: S-EPMC7876358 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: The recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia. METHODS: We determined the rs10892151 genotype distribution and serum apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n = 208) and in a group of age and sex-matched healthy volunteers (n = 200). Circulating lipid and lipoprotein levels were followed for 12 months after antiretroviral treatment initiation in the HIV-infected group. RESULTS: There were no significant variations in the frequency of the A allele between the healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7); additionally, the A allele was not related to serum apo C-III concentration. However, among patients receiving protease inhibitor (PI) treatment, carriers of the A allele had significantly increased serum triglyceride (5.76 ± 2.54 mmol/L) and total cholesterol (6.63 ± 2.85 mmol/L) concentrations together with depressed levels of HDL-cholesterol (0.75 ± 0.3 mmol/L) when compared with patients not carrying the allele (2.43 ± 1.32, 5.2 ± 2.17 and 1.24 ± 0.4 mmol/L, respectively) at the end of the study. This effect was only evident for HDL-cholesterol concentration when patients were treated with non-nucleoside reverse transcriptase inhibitors (1.05 ± 0.4 vs. 1.28 ± 0.4 mmol/L). CONCLUSIONS: The A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs.
| S-EPMC3189871 | biostudies-literature
Project description:BackgroundData describing the true extent of antiretroviral therapy (ART)-induced dyslipidemia and insulin resistance in perinatally infected children on ART in Africa are sparse.MethodsFasting total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, insulin and glucose were performed on the first 100 of 190 pediatric ART clinic attendees. Diet assessment was performed by a trained dietician. Lipoatrophy was formally graded by consensus between 2 expert HIV pediatricians. Durations of previous ART exposures, clinical stage, pre-ART viral load, nadir and current CD4 were recorded. Dual-energy X-ray absorptiometry was performed on a subset of 42 patients selected semi-randomly.ResultsPrevalences of insulin resistance, abnormal total cholesterol, LDL, HDL and triglyceride were 10%, 13%, 12%, 13% and 9%, respectively. Overall, 40% had at least 1 lipid abnormality or insulin resistance. Adjusted mean LDL cholesterol increased by 0.24 mmol/L for each additional year of cumulative lopinavir/r exposure (P = 0.03) after correcting for age, gender, body mass index, previous stavudine exposure, age at ART initiation, dietary fat and refined carbohydrate, whereas adjusted mean LDL cholesterol was 0.9 mmol/L higher in children exposed to efavirenz within the previous 6 months (P = 0.02). Adjusting for age, gender and ethnicity, dual-energy X-ray absorptiometry revealed that greater trunk fat and lower peripheral subcutaneous fat were associated with elevated triglycerides but not with total cholesterol, LDL, HDL or homeostatic model assessment. Similarly, the presence of visually obvious lipoatrophy was associated with elevated triglycerides but not with total cholesterol, LDL, HDL, homeostatic model assessment or lactate.ConclusionsPrevalences of insulin resistance and dyslipidemia were high. Cumulative lopinavir is an independent risk factor for dyslipidemia, with efavirenz exposure having only transitory effect.
| S-EPMC4707556 | biostudies-literature
Project description:Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group.A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area.Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4 cell count, HIV viral load and sputum culture for tuberculosis were performed.A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8-7.5) and 6.1 (interquartile range 3.6-8.4) years, respectively. Median CD4 cell count was 726 cells/?l, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n?=?1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P?<?0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889?m, respectively, P?<?0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P?=?0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P?=?0.025). No participant tested positive for Mycobacterium tuberculosis.In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.
| S-EPMC5106089 | biostudies-other
Project description:Balance disorders have been poorly investigated and somewhat neglected in people infected with the human immunodeficiency virus, especially in children, whose have intrinsic and extrinsic risk factors that may compromise the balance. To evaluate the foot plantar pressures and the balance in children with acquired immunodeficiency. We recruited 53 children aged between 6 and 15 years: 33 healthy children, and 20 children with positive serology for the human immunodeficiency virus. A physical examination included anthropometric, reflexes, tactile sensitivity of the foot and orthopedic evaluation. We also collected data of them using Pediatric Equilibrium Scale, baropodometry, and stabilometry. We considered significance level of 0.05 for statistics. Both groups were aged-, sex-matched and similar body mass index and scores of the Pediatric Equilibrium Scale. Three infected children had altered tactile sensitivity, and none had orthopedic or reflex alteration. Infected children had higher mean plantar pressure in the hindfoot than of the control group (p = 0.02). There was higher maximum plantar pressure in the hindfoot of the infected children than of the controls (p = 0.04). Controls had lower maximum plantar pressure in the forefoot than the infected children (p = 0.04). Infected children had larger displacement of the center of pressure (p = 0.006), larger mean velocity of displacement (p = 0.006), and longer duration between successive peaks of displacement than the controls (p = 0.02). Children living with the human immunodeficiency virus discharges great plantar pressures in the hindfoot and to present balance disturbances in the absence of neurological symptomatology.
| S-EPMC6416285 | biostudies-other
Project description:BackgroundWorldwide prevalence of dyslipidemia in HIV-infected children on antiretroviral medications (ARVs) is rising due to extensive use of treatment during their entire lives. Dyslipidemia is the potential side effect of ARVs, especially in individuals taking protease inhibitors. The objective of this study was to determine the prevalence of dyslipidemia in HIV-infected children on ARVs receiving care at Kilimanjaro Christian Medical Centre (KCMC) in Tanzania.MethodsThis was a cross-sectional hospital-based study conducted from September 2015 to May 2016 at KCMC. HIV-infected children and adolescents less than 17 years on ARVs for more than 6 months were enrolled. Blood samples were taken to determine levels of triglycerides (TGs), total cholesterol, lipoproteins (including low-density lipoprotein (LDL) and high-density lipoprotein (HDL)), CD4+ T cells, and viral load (VL). Anthropometric measurements were used to assess nutritional status. SPSS 20.0 was used for analysis. Logistic regression estimated odds ratio (OR) and 95% confidence interval (CI), and P value <.05 was considered significant. Written consent was obtained from parents/guardians on behalf of their children and assent for older children.ResultsA total of 260 participants were included in the study; the median age at HIV diagnosis was 3 (interquartile range (IQR) = 1-6) years. The overall prevalence of dyslipidemia was 46.5% with hypercholesterolemia (⩾200 mg/dl) of 11.2%, HDL (<35 mg/dl) of 22.7%, LDL (⩾130 mg/dl) of 7.7%, and hyperglyceridemia (TG ⩾150 mg/dl) of 12.3%. Children aged between 6 and 12 years at HIV diagnosis had 2.7 times higher odds of developing dyslipidemia compared with younger age at diagnosis (OR = 2.7; 95% CI = 1.1-6.6). Patients with advanced (OR = 6.4; 95% CI = 1.5-27.1) or severe (OR = 9.8; 95% CI = 1.2-76.5) HIV-associated immunodeficiency at diagnosis had higher odds of developing dyslipidemia. Protease inhibitor use was associated with higher odds of developing dyslipidemia (OR = 3.1; 95% CI = 1.4-7.1).ConclusionLate diagnosis of HIV at 6 years of age or more, advanced, or severe immunosuppression, and the use of protease inhibitors were independent predictors of dyslipidemia in children on ARVs after 6 months of treatment, and with low HDL levels observed most commonly. Monitoring lipid profiles in children, especially those on protease inhibitors and with advanced/severe immunosuppression at diagnosis, may help in preventing future complications.
| S-EPMC7453455 | biostudies-literature
Project description:OBJECTIVES:To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. DESIGN:Observational analysis within a randomized trial. METHODS:Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. RESULTS:Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n?=?582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P?<?0.05) and menarche (P?=?0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P?<?0.05) in both sexes and pre-ART BMI-for-age in girls (P?<?0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P?<?0.01). CONCLUSION:Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children.
| S-EPMC4342414 | biostudies-literature
Project description:For HIV-infected children, adherence to antiretroviral therapy (ART) is often assessed by caregiver report but there are few data on their validity. We conducted prospective evaluations with 191 children ages 0-14 years and their caregivers over 6 months in western Kenya to identify questionnaire items that best predicted adherence to ART. Medication Event Monitoring Systems(®) (MEMS, MWV/AARDEX Ltd., Switzerland) electronic dose monitors were used as external criterion for adherence. We employed a novel variable selection tool using the LASSO technique with logistic regression to identify items best correlated with dichotomized MEMS adherence (?90 or <90 % doses taken). Nine of 48 adherence items were identified as the best predictors of adherence, including missed or late doses in the past 7 days, problems giving the child medicines, and caregiver-level factors like not being present at medication taking. These items could be included in adherence assessment tools for pediatric patients.
| S-EPMC4393778 | biostudies-literature
Project description:There have been no paediatric randomised trials describing the effect of planned treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56). Carers, and children if appropriate, completed questionnaires on adherence to ART and acceptability of PTIs. There was no difference in reported adherence on ART between CT and PTI groups; non-adherence (reporting missed doses over the last 3 days or marking <100 % adherence since the last clinical visit on a visual analogue scale) was 18 % (20/111) and 14 % (12/83) on carer questionnaires in the CT and PTI groups respectively (odds ratios, OR (95 % CI) = 1.04 (0.20, 5.41), ?(2) (1) = 0.003, p = 0.96). Carers in Europe/USA reported non-adherence more often (31/121, 26 %) than in Thailand (1/73, 1 %; OR (95 % CI) = 54.65 (3.68, 810.55), ?(2) (1) = 8.45, p = 0.004). The majority of families indicated they were happy to have further PTIs (carer: 23/36, 64 %; children: 8/13, 62 %), however many reported more clinic visits during PTI were a problem (carer: 15/36, 42 %; children: 6/12, 50 %).
| S-EPMC3548111 | biostudies-other
Project description:The objective of this study was to describe lipid profiles and glucose homeostasis in HIV-positive children after initiating or changing antiretroviral therapy and their associations with viral, immune, antiretroviral therapy, and growth factor parameters.Ninety-seven prepubertal HIV-positive children aged 1 month to <13 years were observed for 48 weeks after beginning or changing antiretroviral therapy. Fasting lipid panels, serum glucose, insulin, insulin-like growth factor-1 and binding proteins-1 and -3, plasma viral load, and CD4% were measured. Each child was matched on age, gender, and race/ethnicity to children from the National Health and Nutrition Examination Survey, used to give z scores for each child's lipid values. Multivariate regression was used to evaluate the association of changes in z scores over 48 weeks with suppression of HIV-1 RNA, change in CD4% and growth factors, and antiretroviral therapy, adjusted for entry z score, CD4%, log(10) HIV-1 RNA, Centers for Disease Control and Prevention category, and total fat and cholesterol dietary intake.Lipid, apolipoprotein, and insulin levels all increased significantly by 48 weeks. Multivariate analysis of changes demonstrated that increased HDL and decreased total-HDL cholesterol ratio were associated with CD4% increase and with insulin-like growth factor-1, which increased to normal (versus remained stable or became low) over 48 weeks. Total cholesterol levels increased among children who achieved HIV-1 RNA of <400 copies per mL. Antiretroviral therapy regimens that included both a protease inhibitor and a non-nucleoside reverse transcriptase inhibitor were associated with greater increases in total-HDL cholesterol ratio than regimens that contained a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor but not both.In these HIV-positive children with predominantly mild-to-moderate disease, initiation or change in antiretroviral therapy was associated with significant increases in multiple lipid measures and insulin resistance. Favorable lipid changes were associated with CD4% increases, suggesting a protective effect of immune reconstitution on atherosclerosis, and with increased insulin-like growth factor-1 levels, supporting the theory that reduced growth hormone resistance may be a mechanism by which lipid profiles are improved. Finally, antiretroviral therapy regimens that contain both a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor are associated with worse lipid profiles than regimens that contain 1 but not both of these drug classes.
| S-EPMC2782494 | biostudies-literature
Project description:BackgroundAntiretroviral therapy (ART) has decreased mortality so that increasing numbers of children with HIV are reaching adolescence. However, longstanding HIV infection and/or its treatment in children is associated with noninfectious complications including cardiac disease. We investigated the prevalence, spectrum and risk factors for echocardiographic abnormalities among children established on ART.MethodsHIV-infected children aged 6-16 years, on ART at least 6 months were enrolled into a cross-sectional study from a public-sector paediatric HIV clinic in Harare, Zimbabwe. A standardized examination including transthoracic echocardiography was performed. Local echocardiographic reference ranges were used to define cardiac abnormalities. Logistic regression was used to examine the association between cardiac abnormalities and risk factors.ResultsOf the 201participants recruited, 92 (46%) were girls and median age was 11 (IQR 9-12) years; CD4+ cell count was 727?cells/?l (IQR 473-935) and 154 (78%) had viral load less than 400?copies/ml. Echocardiographic abnormalities were found in 83 (42%); left ventricular (LV) diastolic dysfunction was the most common abnormality 45 (23%) and LV hypertrophy in 22 (11%). LV and left atrial dilatation were found in 9 (5%) and 16 (8%), respectively. Right ventricular dilatation and systolic dysfunction were found in 13 (7%) and 4 (2%), respectively, of whom 60% had concurrent left heart abnormalities. Current use of nevirapine was associated with LVH [aOR 3.14 (1.13-8.72; P?=?0.03)] and hypertension was associated with LV diastolic dysfunction [aOR 3.12 (1.48-6.57; P?<?0.01)].ConclusionHIV-infected children established on ART have a high burden of echocardiographic abnormalities. Right heart disease was predominantly associated with left heart abnormalities and may be part of a global cardiomyopathic process. Further studies are needed to investigate the natural history, aetiology, and pathogenesis of these abnormalities, so that appropriate monitoring and treatment strategies can be developed.
| S-EPMC6250247 | biostudies-literature