| 1. |
- Chala, A, et al.
(author)
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Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study
- 2021
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In: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Journal article (peer-reviewed)abstract
- (1) Background: Efavirenz plasma concentration displays wide between-patient variability partly due to pharmacogenetic variation and autoinduction. Pediatric data on efavirenz pharmacokinetics and the relevance of pharmacogenetic variation are scarce, particularly from sub-Saharan Africa, where >90% of HIV-infected children live and population genetic diversity is extensive. We prospectively investigated the short- and long-term effects of efavirenz auto-induction on plasma drug exposure and the influence of pharmacogenetics among HIV-infected Ethiopian children. (2) Method: Treatment-naïve HIV-infected children aged 3–16 years old (n = 111) were enrolled prospectively to initiate efavirenz-based combination antiretroviral therapy (cART). Plasma efavirenz concentrations were quantified at 4, 8, 12, 24, and 48 weeks of cART. Genotyping for CYP2B6, CYP3A5, UGT2B7, ABCB1, and SLCO1B1 common functional variant alleles was performed. (3) Results: The efavirenz plasma concentration reached a peak at two months, declined by the 3rd month, and stabilized thereafter, with no significant difference in geometric mean over time. On average, one-fourth of the children had plasma efavirenz concentrations ≥4 µg/mL. On multivariate analysis, CYP2B6*6 and ABCB1c.3435 C > T genotypes and low pre-treatment low-density lipoprotein (LDL) were significantly associated with higher plasma efavirenz concentration regardless of treatment duration. Duration of cART, sex, age, nutritional status, weight, and SLCO1B, CYP3A5, UGT2B7, and ABCB1 rs3842 genotypes were not significant predictors of efavirenz plasma exposure. (4) Conclusion: Pre-treatment LDL cholesterol and CYP2B6*6 and ABCB1c.3435 C > T genotypes predict efavirenz plasma exposure among HIV-infected children, but treatment-duration-dependent changes in plasma efavirenz exposure due to auto-induction are not statistically significant.
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| 2. |
- Frank, TD, et al.
(author)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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In: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
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Journal article (peer-reviewed)
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| 6. |
- Tadesse, BT, et al.
(author)
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HIV and cART-Associated Dyslipidemia Among HIV-Infected Children
- 2019
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:4
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Journal article (peer-reviewed)abstract
- Background: Persistent dyslipidemia in children is associated with risks of cardiovascular accidents and poor combination antiretroviral therapy (cART) outcome. We report on the first evaluation of prevalence and associations with dyslipidemia due to HIV and cART among HIV-infected Ethiopian children. Methods: 105 cART naïve and 215 treatment experienced HIV-infected children were enrolled from nine HIV centers. Demographic and clinical data, lipid profile, cART type, adherence to and duration on cART were recorded. Total, low density (LDLc) and high density (HDLc) cholesterol values >200 mg/dL, >130 mg/dL, <40 mg/dL, respectively; and/or, triglyceride values >150 mg/dL defined cases of dyslipidemia. Prevalence and predictors of dyslipidemia were compared between the two groups. Results: prevalence of dyslipidemia was significantly higher among cART experienced (70.2%) than treatment naïve (58.1%) children (p = 0.03). Prevalence of low HDLc (40.2% versus 23.4%, p = 0.006) and hypertriglyceridemia (47.2% versus 35.8%, p = 0.02) was higher among cART experienced than naïve children. There was no difference in total hypercholesterolemia and high LDLc levels. Nutrition state was associated with dyslipidemia among cART naïve children (p = 0.01). Conclusion: high prevalence of cART-associated dyslipidemia, particularly low HDLc and hypertriglyceridemia was observed among treatment experienced HIV-infected children. The findings underscore the need for regular follow up of children on cART for lipid abnormalities.
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| 7. |
- Tadesse, BT, et al.
(author)
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Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia
- 2019
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In: Viruses. - : MDPI AG. - 1999-4915. ; 11:9
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Journal article (peer-reviewed)abstract
- Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.
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| 8. |
- Tadesse, BT, et al.
(author)
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Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study
- 2019
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In: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 8:4
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Journal article (peer-reviewed)abstract
- There is limited data on virologic outcome and its correlates among HIV-infected children in resource-limited settings. We investigated rate and correlates of virologic outcome among treatment naïve HIV-infected Ethiopian children initiating cART, and were followed prospectively at baseline, 8, 12, 24 and 48 weeks using plasma viral load, clinical examination, laboratory tests and pretreatment HIV drug resistance (PDR) screening. Virologic outcome was assessed using two endpoints–virological suppression defined as having “undetectable” plasma viral load < 150 RNA copies/mL, and rebound defined as viral load ≥150 copies/mL after achieving suppression. Cox Proportional Hazards Regression was employed to assess correlates of outcome. At the end of follow up, virologic outcome was measured for 110 participants. Overall, 94(85.5%) achieved virological suppression, of which 36(38.3%) experienced virologic rebound. At 48 weeks, 9(8.2%) children developed WHO-defined virological treatment failure. Taking tenofovir-containing regimen (Hazard Ratio (HR) 3.1-[95% confidence interval (95%CI) 1.0–9.6], p = 0.049) and absence of pretreatment HIV drug resistance (HR 11.7-[95%CI 1.3–104.2], p = 0.028) were independently associated with earlier virologic suppression. In conclusion, PDR and cART regimen type correlate with rate of virologic suppression which was prominent during the first year of cART initiation. However, the impact of viral rebound in 38.3% of the children needs evaluation.
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