Advanced World Health Organization Research Articles

Predictors of CD4 cell count progression over time among adolescents and young adults transitioning to adult-oriented HIV care in Southern Ethiopia from 2017 to 2021: a retrospective cohort study

BackgroundHuman immunodeficiency virus (HIV), a viral infection impacting CD4 cells, requires an understanding of factors influencing CD4 cell counts to reduce acquired immunodeficiency syndrome(AIDS)-related morbidity and mortality. Despite its importance, no studies have examined predictors of CD4 cell count progression post-transition to adult-oriented HIV care in Ethiopia. This study aimed to identify predictors affecting CD4 cell count trends among adolescents and young adults transitioning to adult-oriented HIV care. Therefore, this study aimed to identify the predictors that affect the trends of CD4 cell count over time among adolescents and young adults who transitioned to adult-oriented HIV care.MethodsA retrospective cohort study was conducted among 206 adolescents and young adults who transitioned to adult-oriented HIV care and had at least two CD4 cell counts in eight selected health facilities in Southern Ethiopia. These facilities were chosen due to their high volume of people living with HIV. A multivariable linear mixed effect model was fitted to identify the predictors of CD4 cell count progression through time. Multi-collinearity between variables was checked using the variance inflation factor. Model comparisons were done using Akaike and Bayesian information criteria. Regression coefficients with 95% confidence intervals (CI) and P-value ≤ 0.05 were used to measure the strength of association and significance level.ResultsThe average CD4 cell count was raised by 6.7 cells/mm3 every six months among the study participants. Transitioning at the age of 18 or older (β = 204.71; 95% CI = 81.86347, 327.5574; P < 0.001), being rural residents (β= -119.776; 95% CI = -215.362, -24.189; P < 0.014), having World Health Organization (WHO) stage III & IV HIV (β= -182.161; 95% CI = -318.475, -45.847; P < 0.009), were the predictors for CD4 cell count progression over time.ConclusionBased on the identified predictors of CD4 cell count progression over time among HIV-positive adolescents and young adults transitioning to adult-oriented HIV care in southern Ethiopia, such as observation time, age at transition, residence, and WHO staging, the study highlights the need for interventions focused on tailored support. Specifically, these interventions should target individuals transitioning with less ART time, those younger than 18, those residing in rural areas, and those with advanced WHO staging, to improve their CD4 cell counts over time.

Assessing renal function with the use of cystatin C in a rural cohort of people living with HIV on highly active antiretroviral therapy within the Limpopo Province, South Africa

The kidneys in people living with HIV (PLWH) are constantly exposed to highly antiretroviral therapy (HAART) which may cause renal dysfunction. Cystatin C (CystC), a biomarker of renal function, is well associated with renal impairment in various populations, however, it is underexplored in the South African population of PLWH, as compared to creatinine-based measurements. Creatinine-based measurements for assessing kidney function in people with HIV can be limited due to the influence of muscle wasting, altered creatinine metabolism, and the potential for certain antiretroviral medications to impact creatinine secretion. Therefore, the current study aimed to explore the effect of HAART on renal function among PLWH with the use of Cyst C-based measures. We conducted a cross-sectional study of 111 adults PLWH, 84 on HAART, and 27 on HAART-naïve. The cluster of differentiation 4 (CD4 +) count, plasma CystC, as well as the estimated glomerular filtration rate (eGFR) using the chronic kidney disease-epidemiology collaboration (CKD-EPI) formula, were determined. In the present study, no significant differences were observed between HAART-treated and HAART-naïve groups in terms of plasma CystC and eGFRCystC. Participants who were on HAART for > 5 years were significantly associated with eGFRCystC < 90 mL/min/1.73 m2, as indicated by substantial odds ratio of 4.39 (confidence interval: 1.60–12.02, p = 0.004) in the unadjusted analysis and even after adjustment for age, sex and smoking status, with odds ratio of 4.10 (confidence interval: 1.41–11.86, p = 0.009). Advanced World Health Organization (WHO) clinical stage significantly associated with eGFRCystC < 90 mL/min/1.73 m2 as indicated by odds ratio of 11.73 (confidence interval: 2.27–60.75, p = 0.003) in the unadjusted analysis. Even after adjusting for confounders which included age, sex, and smoking status, the association persisted, with an odds ratio of 16.71 (confidence interval: 2.57–108.75, p = 0.003). In conclusion, CystC and eGFRCystC levels were not different between PLWH on HAART and not on HAART but prolonged HAART use for over five years and advanced HIV disease were associated with reduced renal function in this population of PLWH on HAART, as assessed using CystC-based measures. These findings may suggest that HAART had initial beneficial effects and long-term adverse effects. The future risk of progressive eGFR decline may be increased in this HIV population on HAART due to the cumulative effect of prolonged tenofovir disoproxil fumarate (TDF) use. These findings remain important to guide future research with larger populations on the management of conditions related to renal function decline in PLWH.Highlights.

Time to develop adverse drug reactions and associated factors among children HIV positive patients on antiretroviral treatment in North West Amhara Specialized Hospitals: Retrospective cohort study, 2022.

Adverse drug reactions (ADRs) are harmful and unintended reactions to medicines given at standard doses through a proper route of administration for the purpose of prophylaxis, diagnosis, or treatment. The objective of this research paper was to assess median time to development of ADRs and associated factors among children HIV positive patients on antiretroviral treatment (ART) in North West Amhara Specialized Hospitals. The adverse drug effect survival time was estimated using the Kaplan-Meier survival method and log-rank test curves was applied for analyze "time-to-event" data. Cox regression model was used to identify the associated factors. Adjusted hazard ratios with their respective 95% confidence intervals (CIs) were estimated and a value of p less than 0.05 was used to declare the presence of a significant association. The overall incidence of ADRs was 0.67 (95% CI: 3.74-4.44) per 10,000 person-year observation, with a median of 57 months. Adults are presenting with opportunistic Infections (OIs) experiences, baseline CD4 < 200 cells/µL counts, 1e, tenofovir disoproxil fumarate-lamivudine-efavirenz ART regimen, bedridden baseline functional status, World Health Organization (WHO) clinical stage II and III were notably associated with the incidence of ADRs development. ADRs were uncommon in this study. predictors, such as OIs experiences, a low CD4 count, ART regimen, an advanced WHO stage, and bedridden functional status were significantly associated with ADRs.

Incidence and Predictors of Severe Adverse Drug Reactions among Patients on Antiretroviral Drugs in Harari Regional State, Eastern Ethiopia.

The introduction of combination antiretroviral therapy improves the quality and longevity of people living with HIV/AIDS. However, adverse drug reactions associated with antiretroviral therapy compromise the resulting benefits and have been reported differently worldwide, including Ethiopia. Severe adverse drug reactions are one of the major public health concerns for the reason that they can potentially impede the benefit of antiretroviral therapy and put the patient's survival at risk. Despite many successes achieved with the introduction of the combined antiretroviral therapy, the majority of the patients on antiretroviral therapy experience adverse drug reactions associated with the drugs. Consequently, little is known about the problem in the current study area. This is, therefore, to study incidence and predictors of severe adverse drug reactions among patients on antiretroviral drugs in the Harari region, Eastern Ethiopia. The aim of this study was to assess the incidence and predictors of severe adverse drug reactions among patients on antiretroviral therapy from February 25, 2022, to March 25, 2022, in the Harari region, Eastern Ethiopia. A hospital-based retrospective cohort study was conducted among 449 randomly selected medical records of people living with HIV on first-line antiretroviral therapy. Collected data were entered into EpiData version 3.1 and exported to STATA version 15 for analysis. Kaplan-Meier survival curve with log-rank test was used to compare survival curves for categorical independent variables. A p value ≤0.05 was declared as significant, and an adjusted hazard ratio was used to report the effect size using the multivariate Cox proportional hazard model. The overall incidence density of the severe adverse reactions was 7.22 per 1000 months (95% CI: 5.5, 9.6). After adjusting for all potential confounders using multivariable Cox proportional hazard ratio, advanced clinical diseases (AHR = 3.44; 95% CI: 1.54, 7.65), HIV/tuberculosis confections (AHR = 2.38; 95% CI: 1.23, 4.62), and being female (AHR = 3.12; 95% CI: 1.57, 6.18) were significantly associated with the experience of severe adverse drug reactions. In this study, the incidence of severe adverse reactions was consistent with the previous studies, and advanced World Health Organization (WHO) clinical stage, HIV/TB confection, and being female were the independent predictors of the severe adverse drug reactions.

Incidence and Predictors of Major Adverse Drug Reactions Among Human Immunodeficiency Virus–infected Children on Antiretroviral Treatment in West Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia: A Multicenter Retrospective Follow-up Study

PurposeMajor adverse drug reactions (ADRs) are the leading causes of poor adherence, switching of drugs, morbidity, and mortality. A limited studies was conducted to investigate major ADR in developing countries including Ethiopia, and the purpose of this study was to assess the incidence and predictors of major ADRs among HIV-infected children receiving antiretroviral therapy (ART) in West Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia. MethodsAn institutional-based retrospective follow-up study was conducted among 460 children receiving ART from January 1, 2014 to December 31, 2021. A simple random sampling technique was employed, and data were collected using Kobo Toolbox software and then deployed to STATA 14 for analysis. The Kaplan-Meier survival curve and the log-rank test were used to estimate and compare survival times. Both bivariable and multivariable Weibull regression models were fitted to identify predictors. Finally, an adjusted hazards ratio (AHR) with a 95% CI was computed, and variables with P < 0.05 were considered statistically significant predictors of major ADR. FindingsThe overall incidence rate of major ADRs was 5.8 (95% CI, 4.6–7.3) per 1000 child months. Being female (AHR, 2.71; 95% CI, 1.52–4.84), tuberculosis (TB)–HIV co-infection (AHR, 2.49; 95% CI, 1.32–4.68), World Health Organization stage (III and IV) (AHR, 2.52; 95% CI, 1.39–4.56), zidovudine-based (AHR, 2.84; 95% CI, 1.11–7.31), and stavudine-based (AHR, 5.96; 95% CI, 1.63–21.84) regimens were found to be significant predictors of major ADRs. ImplicationsThe major ADR incidence rate was high. Health professionals should employ early screening and close follow-up for children with advanced World Health Organization clinical staging, females, those with TB-HIV co-infection, and those receiving stavudine- and zidovudine-based initial regimens to reduce the incidence of major ADRs.

Adherence to antiretroviral therapy and associated factors among HIV-positive adolescents in Sub-Saharan Africa: a systematic review

Purpose: Although long-term viral suppression and antiretroviral therapy (ART) success depend on sustained adherence, adolescents’ adherence rates are suboptimal. Optimal adherence is influenced by various factors. Since Sub-Saharan Africa is home to over 80% of adolescents living with human immunodeficiency virus (HIV) and considering their unique characteristics and susceptibility to poor adherence, it is crucial to provide updated knowledge on adherence rates and their determinants among this population. This review aims to present up-to-date data on adherence rates and associated factors among HIV-positive adolescents in Sub-Saharan Africa.Methods: A systematic review was conducted following the PRISMA guidelines. The PubMed and Scopus databases were used to identify documents corresponding to the study's objectives. Eleven studies were included in this review after being selected from among all studies that were found online from 2017 to 2023. Results: The reported adherence rates ranged from 55% to 86%. In total, 32 factors were found to be related to adherence among HIV-positive adolescents in Sub-Saharan Africa. These included 12 adherence-facilitating factors and 20 adherence-inhibiting factors. The most often mentioned factors affecting adherence were advanced World Health Organization clinical stage (i.e., stage IV), ART dose and regimens, a lack of support, and violence victimization. Conclusion: Our findings can help healthcare providers collaborate with HIV-positive adolescents to improve ART adherence and ensure the best possible health outcomes.

Current insights into the oncogenic roles of lncRNA LINC00355.

Long noncoding RNAs (lncRNAs) are a class of nonprotein-coding transcripts that are longer than 200 nucleotides. LINC00355 is a lncRNA located on chromosome 13q21.31 and is consistently upregulated in various cancers. It regulates the expression of downstream genes at both transcriptional and posttranscriptional levels, including eight microRNAs (miR-15a-5p, miR-34b-5p, miR-424-5p, miR-1225, miR-217-5p, miR-6777-3p, miR-195, and miR-466) and three protein-coding genes (ITGA2, RAD18, and UBE3C). LINC00355 plays a role in regulating various biological processes such as cell cycle progression, proliferation, apoptosis, epithelial-mesenchymal transition, invasion, and metastasis of cancer cells. It is involved in the regulation of the Wnt/β-catenin signaling pathway and p53 signaling pathway. Upregulation of LINC00355 has been identified as a high-risk factor in cancer patients and its increased expression is associated with poorer overall survival, recurrence-free survival, and disease-free survival. LINC00355 upregulation has been linked to several unfavorable clinical characteristics, including advanced tumor node metastasis and World Health Organization stages, reduced Karnofsky Performance Scale scores, increased tumor size, greater depth of invasion, and more extensive lymph node metastasis. LINC00355 induces chemotherapy resistance in cancer cells by regulating five downstream genes, namely HMGA2, ABCB1, ITGA2, WNT10B, and CCNE1 genes. In summary, LINC00355 is a potential oncogene with great potential as a diagnostic marker and therapeutic target for cancer.

Prevalence of undernutrition and associated factors among adults taking antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.

Undernutrition (Body Mass Index < 18.5 kg/m2) is a common problem and a major cause of hospital admission for patients living with HIV. Though sub-Saharan Africa is the most commonly affected region with HIV and malnutrition, a meta-analysis study that estimates the prevalence and correlates of undernutrition among adults living with HIV has not yet been conducted. The objective of this study was to determine the pooled prevalence of undernutrition and associated factors among adults living with HIV/AIDS in sub-Saharan Africa. Studies published in English were searched systematically from databases such as PubMed, Google Scholar, and gray literature, as well as manually from references in published articles. Observational studies published from 2009 to November 2021 were included. The data extraction checklist was prepared using Microsoft Excel and includes author names, study area, publication year, sample size, prevalence/odds ratio, and confidence intervals. The results were presented and summarized in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standard. Heterogeneity was investigated using the Q test, I2, τ2, τ and predictive interval. STATA version 17 was used to analyze the data. A meta-analysis using a random-effects model was used to determine the overall prevalence and adjusted odds ratio. The study has been registered in PROSPERO with a protocol number of CRD42021268603. In this study, a total of 44 studies and 22,316 participants were included. The pooled prevalence of undernutrition among adult people living with HIV (PLWHIV) was 23.72% (95% CI: 20.69-26.85). The factors associated with undernutrition were participants' age (AOR = 0.5, 95% CI: 0.29-0.88), gender (AOR = 2.08, 95% CI: 0.22-20.00), World Health Organization (WHO) clinical stage (AOR = 3.25, 95% CI: 2.57-3.93), Cluster of Differentiation 4 (CD4 count) (AOR = 1.94, 95% CI: 1.53-2.28), and duration of ART (AOR = 2.32, 95% CI: 1.6-3.02). The pooled prevalence of undernutrition among adult PLWHIV in sub-Saharan Africa remained high. WHO clinical stage, CD4 count, duration of ART treatment, age, and sex were found to be the factors associated with undernutrition. Reinforcing nutrition counseling, care, and support for adults living with HIV is recommended. Priority nutritional screening and interventions should be provided for patients with advanced WHO clinical stages, low CD4 counts, the male gender, younger age groups, and ART beginners.

Prevalence and determinants of opportunistic infections among HIV-infected adults receiving antiretroviral therapy in Ethiopia: A systematic review and meta-analysis.

Reliable data on the burden of opportunistic infections (OIs) after the initiation of antiretroviral therapy (ART) is critical for planning health services and reducing OI-related morbidity and mortality. Nevertheless, there has been no nationally representative information on the prevalence of OIs in our country. Therefore, we have undertaken this comprehensive systematic review and meta-analysis to estimate the pooled prevalence, and identify factors associated with the development of OIs in Human Immunodeficiency Virus (HIV)-infected adults receiving ART in Ethiopia. Articles were searched in international electronic databases. A standardized Microsoft Excel spreadsheet and STATA software version 16 were used for data extraction and analysis, respectively. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was used to write this report. The random-effect meta-analysis model was used to estimate the pooled effect. The statistical heterogeneity of the meta-analysis was checked. Subgroup and sensitivity analyses were also performed. Publication bias was examined in funnel plots and the nonparametric rank correlation test of Begg and the regression-based test of Egger. Association was expressed through a pooled odds ratio (OR) with a 95% Confidence Interval (CI). A total of 12 studies with 6,163 study participants were included. The pooled prevalence of OIs was 43.97% [95% CI (38.59, 49.34)]. Poor adherence to ART [OR, 5.90, 95% CI (3.05, 11.40)], under nutrition [OR, 3.70, 95% CI (2.01, 6.80)], CD4 T lymphocyte count <200 cells /μL [OR, 3.23 95% CI (2.06, 5.07)], and advanced World Health Organization (WHO) HIV clinical stages [OR, 4.84 95% CI (1.83, 12.82)] were determinants of OIs. The pooled prevalence of OIs among adults taking ART is high. Poor adherence to ART, under nutrition, a CD4 T lymphocyte count <200 cells /μL, and advanced WHO HIV clinical stages were factors associated with the development of OIs.

Incidence and Predictors of Opportunistic Infections Among Adult HIV Infected Patients on Anti-Retroviral Therapy at Dessie Comprehensive Specialized Hospital, Ethiopia: A Retrospective Follow-Up Study.

BackgroundOpportunistic infections are the major causes for morbidity and mortality due to HIV infections. Despite advances in HIV diagnosis and management, the incidence of opportunistic infections remains high. This study aimed to assess the incidence and predictors of opportunistic infections among persons living with HIV/AIDS in Ethiopia.MethodsA retrospective follow-up study was conducted on 354 samples of adults living with HIV on antiretroviral therapy at Dessie Comprehensive Specialized Hospital. Simple random sampling technique was used to select study participants. The data collection format was taken from national antiretroviral intake and follow-up forms. Epi-data Version 4.6.1 and STATA Version 16 software were used for data entry and data analysis respectively. The Cox-proportional hazards regression model was fitted. Kaplan–Meier survival curve was used to estimate opportunistic infections-free survival time. Both bi-variable and multivariable Cox-proportional hazard regression analysis were done to identify predictors of opportunistic infections.ResultsOf the total 354 peoples living with HIV, 114 (32.2%) developed OI, with an incidence rate of 13.5 per 100 person-year (95% CI: 10.8–15.6). Advanced World Health Organization clinical disease stage (IV) (AHR: 2.1 (95% CI: 1.16, 3.8)), being bedridden (AHR: 1.66 (95% CI: 1.04, 2.65)), poor adherence (AHR: 1.7 (95% CI: 1.1–2.63), and low CD4 count (AHR: 1.92 95% CI: 1.14–3.22) were significant predictors of OIs.ConclusionOpportunistic infection among HIV/AIDS continues to be a significant public health concern in Ethiopian health care setting. Our results indicate that the incidence of OI is high. Besides, Stage IV HIV status, being bedridden, low CD4 count and poor adherence independently predicts an increased incidence/decreased survival time of OIs among PLWHIV. Early care-seeking and initiation of HAART and continuous follow-up of patients to take their drug timely are essential to curb the incidence of opportunistic infections and improve overall health. Further research on this area is highly recommended.

The relationship among integrin alpha 7, CD133 and Nestin as well as their correlation with clinicopathological features and prognosis in astrocytoma patients

ObjectiveIntegrin alpha 7 (ITGA7), a potential glioma stem cell marker, regulates several other stem cell markers including CD133 and Nestin in several cancers, meanwhile its high expression is related to poor prognosis in multiple solid tumor patients. However, few studies report correlation of ITGA7 with prognosis in astrocytoma patients. Hence, this study aimed to determine the astrocytoma-tissue ITGA7, CD133 and Nestin expressions to explore their relationship and clinical value for astrocytoma management. MethodsTotally, 124 patients with primary astrocytoma were included. Their tumor tissue ITGA7, CD133 and Nestin expressions were determined by immunohistochemical (IHC) assay and scored by intensity and density ranging from 0 to 12 points. Besides, their clinical features (such as world health organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation, and adjuvant therapy etc.) were collected, also their overall survival (OS) were analyzed by follow-up data. ResultsThe mean IHC scores for ITGA7, CD133 and Nestin were 4.9 ± 2.5, 2.1 ± 2.6 and 5.8 ± 2.6, respectively. Moreover, ITGA7 high expression correlated with absence of IDH mutation (P = 0.004), advanced WHO grade (P = 0.001) and shorter OS (P = 0.005). Besides, ITGA7 positively correlated with CD133 (P = 0.001) and Nestin (P = 0.001) expressions. Regarding CD133 and Nestin, their high expression also correlated with increased WHO grade and shorter OS. Furthermore, multivariant Cox’s regression analysis displayed that only CD133 high expression (P = 0.021) could independently predict reduced OS, while ITGA7 or Nestin high expression could not independently predict that. ConclusionITGA7, CD133, and Nestin are intercorrelated, also their high expressions associate with deteriorating disease conditions and poor prognosis in astrocytoma patients.

Cardiac Catheterization and Hemodynamics in a Multicenter Cohort of Children with Pulmonary Hypertension.

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.

Treatment failure and its associated factors among children receiving highly active antiretroviral therapy in Ethiopia: A systematic review and meta-analysis.

Objectives:Over the last decades, large number of children living with human immunodeficiency virus (HIV) have been successfully enrolled in care and initiated treatment. However, treatment failure is still a major challenge in the track, missing far too many children. National-level evidence on antiretroviral therapy failure and its associated factors among children receiving highly active antiretroviral therapy is required to alleviate this challenge.Methods:PubMed/Medline, EMBASE, CINAHL, Cochrane library, Google, and Google Scholar databases were used to access eligible studies. This meta-analysis was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, Newcastle–Ottawa Scale quality assessment was applied for critical appraisal. Cochran’s Q statistic, funnel asymmetry plot, and Egger’s test were used to assess heterogeneity and publication bias. Random effect model was computed to explore the pooled burden of treatment failure and its associated factors among children living with HIV. Odds ratio with 95% confidence interval was considered to identify associated factors.Result:The overall pooled prevalence of treatment failure among children living with HIV was 16.6%. Whereas virological, immunological, and clinical failure were 4.49%, 5.41%, and 5.71% respectively, where either of parent is deceased (odds ratio = 2.13, 95% confidence interval: 1.4–3.3), opportunistic infection (odds ratio = 1.67, 95% confidence interval: 1.1–2.5), absence of disclosure of status (odds ratio = 1.6, 95% confidence interval: 1.0–2.5), advanced World Health Organization stage (odds ratio = 4.2, 95% confidence interval: 1.6–10.5), and drug substitution (odds ratio = 2.0, 95% CI: 1.5–2.7) were significantly associated factors.Conclusion:The pooled prevalence of treatment failure among children living with HIV in Ethiopia was lower when compared to most African countries. Accordingly, either prevention or early treatment of opportunistic infection and advanced World Health Organization clinical stages, special care for children whose either parents are deceased, advocating disclosure of status, and avoiding drug substitution as much as possible were still needed to prevent treatment failure.

Mother-to-Child Transmission of HIV and Associated Factors Among Exposed Infants in Pastoralist Health Facilities, South Omo Zone, Ethiopia, 2020 - A Retrospective Cross-Sectional Study.

BackgroundAlthough HIV/AIDS is affecting all age groups, it is a primary cause of illness and deaths among children globally. A significant bulk of HIV infections in children under the age of 15 were as a result of vertical transmission, where it accounts for 95% of childhood HIV infections in Ethiopia.ObjectiveTo assess the proportion of mother-to-child transmission (MTCT) of HIV and associated factors among exposed infants on follow-up in pastoralist health facilities, South Omo, Ethiopia.MethodologyA retrospective, cross-sectional study was employed among 228 HIV-exposed infants. Medical records of HIV-exposed infant-mother pairs in the study institutions were extracted. The confirmatory HIV serostatus of every infant was taken at the end of 24 months. Data were entered in Epi Data 4.2 version and exported to SPSS version 25 for final analysis. Multivariable logistic regression analysis was used to identify significant predictor variables at P-value < 0.05.ResultsA total of 228 records were included in the analysis. The rate of HIV transmission was 5.3% (95% CI: 2.6–8.3%). Not receiving antiretroviral prophylaxis at birth (AOR = 5.8, 95% CI: 1.02–33.53), absence of maternal antiretroviral prior to current pregnancy (AOR = 5.6, 95% CI: 1.14–28.1), and mother’s advanced World Health Organization clinical stage of HIV (AOR: 10.5, 95% CI: 1.4–81) were associated with MTCT of HIV.ConclusionThis study identified a high proportion of MTCT among exposed infants in the study area. Not receiving antiretrovirals prior to pregnancy and advanced WHO clinical stage of HIV, and not getting antiretroviral prophylaxis at birth resulted in higher risk of MTCT of HIV. Hence, health workers and policy-makers should offer antiretroviral prophylaxis, put mothers on antiretroviral therapy and limit the stage of HIV at lower WHO clinical stages.

Clinical, immunologic and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals in Addis Ababa, Ethiopia.

BackgroundEthiopia launched free access for antiretroviral therapy in 2005. The number of patients on second line antiretroviral treatment has increased with each passing year. The objectives of this study were to describe the clinical, immunological and virologic outcomes of children and adolescents receiving second line anti-retroviral therapy in two referral hospitals, Yekatit 12 and Zewditu Memorial Hospitals, in Addis Ababa, Ethiopia.MethodsThis was a hospital based retrospective cohort study conducted among children and adolescents aged 18 years and less and receiving a second line antiretroviral drugs. Data was collected using structured questionnaires. Means and percentages were used for nominal variables. Statistical analysis was made using statistical software–SPSS 23.0. Kaplan Meier analysis, long rank test and multivariate Cox proportion model were used to identify factors affecting survival.ResultsA total of 75 children and adolescents were studied with a mean age of 13.28 years (SD: 4) with a mean treatment period on second line regimens of 35.2 months (SD: 21.8 months). Forty-eight participants were experiencing successful measures (in all three parameters) for their second line anti-retroviral treatment. Ten had virologic treatment failure while seven had died. Both treatment failure and death rates were higher within the first two years of treatment. Poor treatment adherence (Adjusted hazard ratio: 5.1 (95% CI: 1.1–23.2; p-value = 0.02)) and advanced World Health Organization clinical stage at start of the second line antiretrovirals (Adjusted hazard ratio: 7.51 (95% CI: 1.35–18.02; p-value = 0.002)) correlated significantly with survival of children and adolescents receiving treatment.ConclusionsThe study describes clinical, immunological and virologic outcomes of second line antiretroviral treatment in a pediatric cohort under care in two hospitals in Addis Ababa, Ethiopia. Poor adherence and pre-treatment advanced clinical stages were predictors of survival.

Pulmonary Hypertension in Patients With COPD: Results From the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA)

Pulmonary hypertension (PH) in COPD is a poorly investigated clinical condition. Which factors determine the outcome of PH in COPD? We analyzed the characteristics and outcome of patients enrolled in the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) with moderate or severe PH in COPD as defined during the 6th PH World Symposium who received medical therapy for PH and compared them with patients with idiopathic pulmonary arterial hypertension (IPAH). The population included incident patients with moderate PH in COPD (n= 68), with severe PH in COPD (n= 307), and with IPAH (n= 489). Patients with PH in COPD were older, predominantly male, and treated mainly with phosphodiesterase-5 inhibitors. Despite similar hemodynamic impairment, patients with PH in COPD achieved a worse 6-min walking distance (6MWD) and showed a more advanced World Health Organization functional class (WHO FC). Transplant-free survival rates at 1, 3, and 5 years were higher in the IPAH group than in the PH in COPD group (IPAH: 94%, 75%, and 55%vsPH in COPD: 86%, 55%, and 38%; P= .004). Risk factors for poor outcomes in PH in COPD were male sex, low 6MWD, and high pulmonary vascular resistance (PVR). In patients with severe PH in COPD, improvements in 6MWD by≥ 30m or improvements in WHO FC after initiation of medical therapy were associated with better outcomes. Patients with PH in COPD were functionally more impaired and had a poorer outcome than patients with IPAH. Predictors of death in the PH in COPD group were sex, 6MWD, and PVR. Our data raise the hypothesis that some patients with severe PH in COPD may benefit from PH treatment. Randomized controlled studies are necessary to explore this hypothesis further. ClinicalTrials.gov; No.: NCT01347216; URL: www.clinicaltrials.gov.

Incidence and predictors of sexually transmitted infections among adult HIV-positive patients receiving antiretroviral therapy at Themba Lethu HIV clinic in Johannesburg, South Africa.

Sexually transmitted infections (STIs) among people living with HIV/AIDS can facilitate the spread of HIV. To estimate STI incidence and identify predictors of STI acquisition among HIV-positive patients during their first 24months of antiretroviral therapy (ART) in Johannesburg, South Africa. We conducted a cohort study using prospectively collected routine data on patients who initiated ART between January 2004 and January 2015 at the Themba Lethu HIV clinic in Johannesburg. Kaplan-Meier analysis was used to estimate STI incidence rates (based on evidence of laboratory diagnosis and STI syndromic treatment prescription records). STI predictors were identified using Cox regression analysis. Among 26 762 adult patients on ART, there were 1 906 (7.1%) cases of STI (incidence 4.8/100 person-years; 95% confidence interval (CI) 4.7 - 5.1). Non-pregnant women were 60% more likely than men to be diagnosed with an STI (adjusted hazard ratio (aHR) 1.6; 95% CI 1.4 - 1.8). The risk of STI decreased with increasing baseline CD4 count (aHR 0.8, 0.5 and 0.4 for CD4 counts 101 - 200, 201 - 350 and &gt;350 cells/µL, respectively, compared with CD4 count &lt;100 cells/µL). Patients with advanced baseline World Health Organization (WHO) clinical stages had a higher risk (aHR 1.6 for WHO stage 4; 95% CI 1.3 - 1.9) compared with those with WHO stage 1. However, there was a 20% increase in the risk of STI among obese patients compared with underweight patients (aHR 1.3; 95% CI 1.0 - 1.7). Over 80% of obese patients diagnosed with an STI had a CD4 count &lt;200 cells/µL. STIs are common in HIV-infected patients who are receiving ART. While both ART and the syndromic management of STIs are high-impact interventions for controlling the spread of HIV, closer monitoring of STI occurrences is warranted, particularly among immunologically vulnerable patients.

YY1-mediated up-regulation of lncRNA LINC00466 facilitates glioma progression via miR-508/CHEK1.

The abnormal expression of lncRNA LINC00466 (LINC00466) has been demonstrated in several tumor types. However, the expression pattern and functions of LINC00466 in glioma remain uninvestigated. A reverse transcriptase-polymerase chain reaction (RT-PCR) was utilized to analyze LINC00466 in human glioma tissues and cell lines. Luciferase reporter assays were performed to explore whether YY1 could bind to the promoter region of LINC00466. Cell counting kit-8, flow cytometry, colony-formation, transwell migration and invasion assays were carried out to determine the involvement of INC00466 in glioma. Luciferase assays and pulldown assays were conducted to verify the binding sites. We report that LINC00466 expression is increased in glioma cells and tissues. YY1 transcription factor (YY1) can bind directly to the LINC00466 promoter region. Clinical studies revealed that the elevated expression of LINC00466 is closely correlated with an advanced World Health Organization grade (p = 0.008), Karnofsky Performance Status score (p = 0.004) and a short overall survival (p = 0.0035) of glioma patients. Functional assays revealed that LINC00466 knockdown distinctly suppresses glioma cell proliferation, migration, invasion and epithelial-mesenchymal progress, and also promotes apoptosis. Moreover, dual-luciferase reporter assays indicated that LINC00466 acts as an endogenous sponge via binding to miR-508 and decreasing its expression. Luciferase assays and RT-PCR assays demonstrated that checkpoint kinase 1 (CHEK1) is a target of miR-508, and LINC00466 modulates CHEK1 levels by competing for miR-508. LINC00466 may exhibit its anti-oncogenic roles through targeting the miR-508/CHEK1 axis. Our findings identified a novel glioma-related long non-coding RNA, LINC00466, which may provide a potential novel prognostic and therapeutic target for glioma.

Temporal trends of early mortality and its risk factors in HIV-infected adults initiating antiretroviral therapy in Uganda.

BackgroundA decline in mortality rates during the first 12 months of antiretroviral therapy (ART) has been mainly linked to increased ART initiation at higher CD4 counts and at less advanced World Health Organization (WHO) clinical stages of HIV infection; however, the role of improved patient care has not been well studied. We estimated improvements in early mortality due to improved patient care.MethodsWe conducted a retrospective cohort study of HIV-infected individuals ages 18 and older who initiated ART at the Mengo HIV Counseling and Home Care Clinic between 2006 and 2016. We conducted a mediation analysis using generalized structural equation models with inverse odds ratio weighting to estimate the natural direct and indirect effects of ART initiation time on early mortality.FindingsAmong 6,847 patients, most were female (69%), with a median age of 32 (interquartile range [IQR] = 28–38), versus a median age of 38 (IQR = 32–45) for males. The median CD4 count at ART initiation increased from 142 cells/ul (95% confidence interval [CI] = 135–150) in 2006–2010 to 302 cells/ul (95% CI = 283–323) in 2015–2016 (p < 0·001). The number of patients at WHO clinical stages I/II increased from 52% in 2006–2010 to 78% in 2015–2016 (p < 0·001). Annual early mortality decreased from 8·8 deaths/100 person years (PYS) in 2006 to 2.5 deaths/100 pys in 2016 (p < 0·001). Mediation by CD4 counts and WHO clinical stages accounted for 54% of the total effect of ART initiation timing on early mortality. In comparison, 46% remained as the direct effect, reflecting the contribution of improved patient care.InterpretationImproved patient care practices should be promoted as a strategy for reducing early mortality after ART initiation, above and beyond the effects from ART initiation at higher CD4 counts and less advanced WHO clinical stage alone.FundingThis research was supported by the President's Emergency Plan for AIDS Relief (PEPFAR), the National Institute of Allergy and Infectious Diseases Division of Intramural Research, and the National Cancer Institute.

Mortality Rate in a Cohort of People Living With HIV in Rural Tanzania After Accounting for Unseen Deaths Among Those Lost to Follow-up.

Mortality assessment in cohorts with high numbers of persons lost to follow-up (LTFU) is challenging in settings with limited civil registration systems. We aimed to assess mortality in a clinical cohort (the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO)) of human immunodeficiency virus (HIV)-infected persons in rural Tanzania, accounting for unseen deaths among participants LTFU. We included adults enrolled in 2005–2015 and traced a nonrandom sample of those LTFU. We estimated mortality using Kaplan-Meier methods 1) with routinely captured data (method A), 2) crudely incorporating tracing data (method B), 3) weighting using tracing data to crudely correct for unobserved deaths among participants LTFU (method C), and 4) weighting using tracing data accounting for participant characteristics (method D). We investigated associated factors using proportional hazards models. Among 7,460 adults, 646 (9%) died, 883 (12%) transferred to other clinics, and 2,911 (39%) were LTFU. Of 2,010 (69%) traced participants, 325 (16%) were found: 131 (40%) had died and 130 (40%) had transferred. Five-year mortality estimates derived using the 4 methods were 13.1% (A), 16.2% (B), 36.8% (C), and 35.1% (D), respectively. Higher mortality was associated with male sex, referral as a hospital inpatient, living close to the index clinic, lower body mass index, more advanced World Health Organization HIV clinical stage, lower CD4 cell count, and less time since initiation of antiretroviral therapy. Adjusting for unseen deaths among participants LTFU approximately doubled the 5-year mortality estimates. Our approach is applicable to other cohort studies adopting targeted tracing.