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  • 1
    In: Antiviral Therapy, SAGE Publications, Vol. 18, No. 5 ( 2013-07), p. 681-690
    Abstract: In Africa, success of antiretroviral treatment (ART) seems to lag behind in children compared with adults, and high therapeutic failure rates have been reported. We aimed to identify prevalence and determinants of virological failure in HIV-infected children treated under programmatic conditions. Methods All patients 〈 18 years on ART presenting to the HIV clinic at the Bamenda Regional Hospital, a secondary referral hospital in rural Cameroon, from September 2010 to August 2011, were enrolled in this cross-sectional study. Clinical data, self-reported adherence, CD4 + T-cell counts and viral load were recorded. Therapeutic drug monitoring was performed on stored plasma samples. Determinants of virological failure were identified using descriptive statistics and logistic regression. Results A total of 230 children with a mean age of 8.9 years (sd 3.7) were included. At the time of analysis, the mean duration of HAART was 3.5 years (sd 1.7) and 12% had a CD4 + T-cell count 〈 200 cells/μl. In total, 53% of children experienced virological failure ( 〉 200 copies/ml). Among children on nevirapine (NVP), plasma levels were subtherapeutic in 14.2% and supratherapeutic in 42.2%. Determinants of virological failure included male sex, lower CD4 + T-cell counts, subtherapeutic drug levels, longer time on ART and a deceased mother. Poor adherence was associated with subtherapeutic NVP plasma levels and advanced disease stages (WHO stage 3/4). Conclusions This study demonstrates high virological failure rates and a high variability of NVP plasma levels among HIV-infected children in a routine ART programme in rural Cameroon. Strategies to improve adherence to ART in HIV-infected children are urgently needed.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
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  • 2
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-7-1)
    Abstract: Background: Despite lopinavir/ritonavir (LPV/RTV) demonstrating in-vitro activity against SARS-CoV-2, large trials failed to show any net clinical benefit. Since SARS-CoV-2 has an EC50 of 16.4 μg/ml for LPV this could be due to inadequate dosing. Methods: COVID-19 positive patients admitted to the hospital who received high dose LPV/RTV were included. High dose (HD) LPV/RTV 200/50 mg was defined as four tablets bid as loading dose, then three tablets bid for up to 10 days. Trough plasma concentrations were measured after the loading dose and on day 5–7 in steady state (SS). Post loading dose (PLD) and SS plasma trough levels were compared with SS trough levels from COVID-19 patients who received normal dose (ND) LPV/RTV (2 tablets bid) at the beginning of the pandemic. Results: Fifty patients (30% female) with a median age of 59 years (interquartile range 49–70.25) received HD LPV/RTV. Median HD-PLD concentration was 24.9 μg/ml (IQR 15.8–30.3) and significantly higher than HD-SS (12.9 μg/ml, IQR 7.2–19.5, p & lt; 0.001) and ND-SS (13.6 μg/ml, IQR 10.1–22.2, p = 0.013). HD-SS and ND-SS plasma levels did not differ significantly ( p = 0.507). C-reactive-protein showed a positive correlation with HD-SS (Spearman correlation-coefficient rS = 0.42, p = 0.014) and ND-SS (rS = 0.81, p = 0.015) but not with HD-PLD (rS = 0.123, p = 0.43). Conclusion: HD-PLD plasma trough concentration was significantly higher than HD-SS and ND-SS concentration, but no difference was detected between HD-SS and ND-SS trough levels. Due to the high EC50 of SARS-CoV-2 and the fact that LPV/RTV is highly protein bound, it seems unlikely that LPV/RTV exhibits a relevant antiviral effect against SARS-CoV-2 in vivo .
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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