|Call||EDCTP Clinical Research & Development Fellowship (R&D F)|
Clinical Research and Development Fellowship
|Workineh Shibeshi||Addis Ababa University College of Health Sciences||Ethiopia|
|Prof.Ephrem Engidawork||Addis Ababa University College of Health Sciences||Ethiopia|
|Department of Pharmacology and Clinical Pharmacy, College of Health Sciences , Addis Ababa University|
|Type||Name||Title||University||Start Date||End Date|
|PhD student||Temesgen Sidamo||Genetic analysis of resistance and PK/PD model based study of moxifloxacin and levofloxacin in MDR-TB patients attending hospitals in Southern Ethiopia||Addis Ababa University||2019||2021|
|PhD study||Wondmagegn Tamiru||Effects of Efavirenz-, Dolutegravir or Ritonavir boosted Atazanavir-based combination antiretrovirals on Glucose metabolism or Drug induced adverse drug effects among treatment experienced HIV/AIDS patients: Pharmacokinetic and Pharmacogenetic study||Addis Ababa University||2019||2021|
|PhD student||Minyahil Alebachew||Bio-markers and incidence of cardio-metabolic syndrome in HIV-infected Ethiopians: a prospective cohort study.||Muhimbili University of Health and Allied Sciences, Tanzania||2019||2021|
|PhD student||Abraham Degaga||Effect of SLC2A2 and SLC22A1 gene Polymorphisms on Glycemic Control and Metformin intolerance in Type 2 Diabetes Patients at St Paul’s Hospital and Zewuditu Memorial Hospital, Addis Ababa, Ethiopia||Addis Ababa University||2019||2021|
|PhD student||Solomon Assefa||Pharmacogenetic study or warfarin in Ethiopians||Addis Ababa University||2019||2021|
Addis Ababa University College of Health Sciences
Associate Professor of Pharmacology
Background Atherosclerotic Cardiovascular Disease (ASCVD) is an emerging problem among People living with HIV/AIDS (PLWHA). The current study aimed at determining the risk of ASCVD among PLWHA using the Pooled Cohort Equation (PCE) and the Framingham Risk score (FRS). Methods A hospital-based study was carried out from January 2019 to February 2020 in PLWHA. The prevalence of ASCVD risk was determined in individuals aged between 20 to 79 and 40 to 79 years using the FRS and PCE as appropriate. Chi-square, univariate and multivariate logistic regressions were employed for analysis. Results The prevalence of high-risk ASCVD for subjects aged 20 and above using both tools was 11.5%. For those aged 40 to 79 years, PCE yielded an increased risk (28%) than FRS (17.7%). Using both tools; advanced age, male gender, smoking, and increased systolic blood pressure were associated with an increased risk of ASCVD. Younger age (adjusted odds ratio, AOR) 0.20, 95%CI: 0.004, 0.091; P< 0.001), lower systolic blood pressure (AOR 0.221, 95%CI: 0.074, 0.605 P< 0.004), and lower total cholesterol (AOR 0.270, 95%CI: 0.073, 0.997; p<0.049) were found to be independent predictors of reduced risk of ASCVD. Likewise, younger age (40 to 64 years), female gender, and lower systolic blood pressure were significantly associated with lower risk of ASCVD among patients aged 40 to 79 years using both PCE and FRS.
A considerable number of PLWHA have been identified to be at risk for ASCVD. ASCVD
risk was significantly associated with advanced age, male gender, higher blood pressure,
and smoking using both FRS and PCE. These factors should therefore be taken into
account for designing management strategies.
ABSTRACT Background: While the fast extension of combination antiretroviral therapy (cART) has resulted in significant increases in life expectancy, disorders such as cardiometabolic syndrome (CMetS), which have received less attention, are becoming a major concern in HIV/AIDS patients (PLWHA). Objectives: The purpose of this research was to identify biomarkers and determine the prevalence of CMetS in PLWHA using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools. Methods: Between January 2019 and February 2021, a hospital-based study of HIV-infected patients (n=288) was conducted. The data were analyzed using binary logistic regression. To control the effect of confounders, independent variables with a P-value of <.20 in the bivariate logistic regression were incorporated into multivariate logistic regression. Statistical significance was defined as a 95% confidence interval and a P-value of less than .05. Results: The risk of CMetS increased twofold as age increased each year (P=.009), 1.2 times as the age at which cART began increased (P=.015), and 6 times with 1 or more co-morbidities (P=.028), according to the NCEP tool. Furthermore, significant NCEP-CMetS correlations were produced by a rise in diastolic blood pressure (P < .001) and cART duration (P=.006). Male gender was 99.9% less likely to be related to CMetS using the IDF tool, and the risk of CMetS increased fourfold with each unit increase in waist circumference (P < .001). Triglycerides and blood type “A” have been found to have substantial relationships with CMetS using both techniques. Conclusion: According to the study, CMetS was found to be common in PLWHA. Age, time on cART, age when cART started, gender, co-morbidities, waist circumference, and diastolic blood pressure were all revealed to be significant predictors of CMetS. Triglycerides and blood type “A” were the only biomarkers found to be significant with CMetS using both the NCEP and IDF tools. Keywords: Biomarkers, Cardiometabolic syndrome (CMetS), Combination Antiretroviral Treatment (cART), Human Immunodeficiency Virus (HIV), Prevalence, Zewditu Memorial Hospita
Purpose/Background: Although Ethiopia is among the thirty high multi-drug resistant tuberculosis (MDR-TB) burden countries in the world, comparative therapeutic efficacy of moxifloxacin and levofloxacin has not been explored, particularly in MDR-TB patients. We therefore aimed to prospectively compare clinical outcomes and determine potential predictors of the outcomes among patients on moxifloxacin or levofloxacin-based MDR-TB drug regimens. Methods: We analyzed clinical parameters and laboratory data of eighty MDR-TB patients on moxifloxacin- or levofloxacin-based regimens. The clinical outcomes were compared using the Kaplan–Meier survival functions and the outcome definitions of the 2013 World Health Organization. Monthly sputum culture conversions and a molecular line probe assay results were also assessed. Observed outcomes and patient-related variables between the two groups were compared using chi-square, Wilcoxon Rank and Fisher exact tests. We also determined the potential predictors influencing treatment outcomes of moxifloxacin and levofloxacin using Cox proportional hazard model. Results: The levofloxacin-based treatment group had a lower failure rate and adverse drug events as well as better treatment success than the moxifloxacin-based group. Overall treatment success was 65%. Disaggregating the data revealed that 53.8% were cured, 11.2% completed treatment, 10.0% died, 11.2% failed, and 13.8% were lost-to-follow-up. The line probe assay result showed that 11.3% of the clinical isolates were resistant to fluoroquinolones and 3.8% were resistant to both fluoroquinolones and injectable anti-TB agents. Treatment regimen type, culture conversion rate, alcohol use, cavity lesion, serum levels of creatinine and alanine aminotransferase were independent predictors of treatment outcome. Conclusion: The levofloxacin-based regimen group has a better overall treatment success than the moxifloxacin-based group among MDR-TB patients. Clinical parameters and substance use history of the patients influenced treatment outcomes. We recommend further broader clinical studies to substantiate our findings as an input to review MDR-TB treatment guidelines. Keywords: MDR-TB, moxifloxacin, levofloxacin, line probe assay, treatment outcome, sputum culture conversion, Ethiopia
We investigated prevalence and predictors of glucose metabolism disorders (GMDs)
among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART).
This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to
The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0–32.6%]
s, with 31.1% (75/240) [95% CI 25.4–37.5%] for efavirenz-based and 19.8% (22/111) [95%
CI 12.9–28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired
fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240);
95%CI (11.1–20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2–
13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age �46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in
both groups. Whereas the male gender and BMI category were predictors of GMDs among
EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were
predictors in the ATV/r-based group
GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age �46
years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for
early diagnosis of type-2 diabetes and management.
Abstract: Long-term antiretroviral treatment (cART) increases the risk of glucose metabolism disorders (GMDs). Genetic variation in drug-metabolizing enzymes and transporters may influence susceptibility to cART-associated GMDs. We conducted a case-control study to investigate the association of pharmacogenetic variations with cART-induced GMDs. A total of 240 HIV patients on long-term efavirenz-based cART (75 GMD cases and 165 controls without GMDs) were genotyped for CYP3A4*1B, CYP3A5 (*3,*6), CYP2B6*6, UGT2B7*2, ABCB1 (c.3435C>T, c.4036A>G), and SLCO1B1 (*1b, *5). GMD cases were defined as the presence of impaired fasting glucose, insulin resistance, or diabetes mellitus (DM). Case-control genotype/haplotype association and logistic regression analysis were performed by adjusting for age, sex, and BMI. The major CYP3A haplotype were CYP3A5*3 (53.8%), CYP3A4*1B (17.3%), combinations of CYP3A4*1B, and CYP3A5*6 (10.9%), and CYP3A wild type (7%). CYP3A5*6 allele (p = 0.005) and CYP3A5*6 genotype (p = 0.01) were significantly associated with GMD cases. Multivariate analysis indicated CYP3A haplotype as a significant predictor of GMD (p = 0.02) and IFG (p = 0.004). CYP2B6*6 significantly predicted DM (p = 0.03). CYP3A haplotype and CYP2B6*6 genotype are independent significant predictors of GMD and DM, respectively, among HIV patients on long-term EFV-based cART.
Malaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas. Artemisinin-based combination therapies (ACTs) are the drugs of choice for malaria management particularly across malaria-endemic countries. This systematic review and meta-analysis was performed to assess efficacy and safety of ACTs for uncomplicated malaria in pediatric populations.
A body of evidence was searched for published ACT trials until March 06, 2020. The search was focused on efficacy and safety studies of ACTs for uncomplicated malaria in pediatrics. PubMed library was searched using best adapted search terms after multiple trials. References were exported to the endnote library and then to Covidence for screening. Data was extracted using the Covidence platform. The per-protocol analysis report for the efficacy and the intention-to-treat analysis for the safety were synthesized. Met-analysis was carried using Open Meta-Analyst software. Random effects model was applied and the heterogeneity of studies was evaluated using I2 statistic.
Nineteen studies were included in the final analysis. Overall, crude, PCR-corrected P. falciparum malaria treatment success rate was 96.3 and 93.9% for day 28 and 42, respectively. In the subgroup analysis, PCR-corrected adequate clinical and parasitological response (ACPR) of dihydroartemisinin-piperaquine (DP) was 99.6% (95% CI: 99.1 to 100%, I2 = 0%; 4 studies) at day 28 and 99.6% (95% CI of 99 to 100%, I2 = 0%; 3 studies) at day 42. Nine studies reported ACT related adverse drug reactions (ADR) (8.3%, 356/4304). The reported drug related adverse reactions ranged from 1.8% in DP (two studies) to 23.3% in artesunate-pyronaridine (AP). Gastrointestinal symptoms were the most common ACT related adverse effects, and all ADRs were reported to resolve spontaneously.
ACTs demonstrated a high crude efficacy and tolerability against P. falciparum. The high treatment success and tolerability with low heterogeneity conferred by DP has implication for policy makers who plan the use of ACTs for uncomplicated falciparum malaria treatment in pediatrics.