The promise of paediatric dolutegravir

Golin, Rachel; Samuel, Jeffrey M.; Phelps, B. Ryan; Persaud, Udita; Malati, Christine Y.; Siberry, George K.

doi:10.1002/jia2.25660

Cited by 12 publications

(11 citation statements)

References 7 publications

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“…While the etiology of hyposalivation and xerostomia associated with caries has been well-described [ 45 ], we were only able to assess hyposalivation as many children did not report a symptom of dry mouth/xerostomia. In addition, xerostomia can occur with hyposalivation [ 54 , 55 ] or without hyposalivation [ 45 ] and be associated with caries. Also, some syrup- or suspension-based antiretroviral medications are sucrose-based [ 1 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

et al. 2022

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Background HIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4–11-year-old Nigerian Children. Methods We used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling. Results HI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0–2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2–9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts. Conclusions We found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored.

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Section: Discussionmentioning

confidence: 99%

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

et al. 2022

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“…This highlights the importance of intensive efforts to diagnose and treat CALHIV as early as possible to preserve immune function, prevent opportunistic infections, and allow these children to thrive. As more robust, effective, and palatable ARTs—such as pediatric DTG 35 —become widely available to CAHLIV, efforts must be made to optimize treatment for children with these preferred regimens as quickly as possible. Targeted differentiated services that address the behavioral, social, and treatment challenges that young children 9 and adolescents 36 face must be a continuous focus of pediatric HIV programs and research.…”

Section: Discussionmentioning

confidence: 99%

Achieving Antiretroviral Therapy Uptake and Viral Suppression Among Children and Adolescents Living With HIV in the UNAIDS 90-90-90 Era Across Six Countries in Eastern and Southern Africa—Lessons From the BIPAI Network

Bacha

Dlamini

Anabwani³

et al. 2022

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…This is especially important as there are expectations for clinical studies in pediatric populations after dolutegravir approval in young children and the development of the drug's pediatric formulation. 29 The chromatographic conditions are similar to an earlier method reported for dolutegravir quantification in plasma using a UV detector and protein precipitation was used for extraction. 12 The use of pioglitazone as an IS in this method means it cannot be used for samples from patients with HIV taking pioglitazone for type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…This is especially important as there are expectations for clinical studies in pediatric populations following dolutegravir approval in young children and the development of the drug’s pediatric formulation. 29 …”

Section: Discussionmentioning

confidence: 99%

Validation and Clinical Application of a Liquid Chromatography–Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots

Akinloye

Eniayewu

Adeagbo

et al. 2022

Therapeutic Drug Monitoring

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Background: Dolutegravir is currently the preferred component of first-line antiretroviral therapy. To facilitate clinical pharmacology studies in key populations, quantitative analytical methods compatible with microsampling and adaptable to resource-limited settings are desirable. The authors developed and validated a liquid chromatography-ultraviolet detection method to quantify dolutegravir in dried blood spots (DBS).Methods: Calibration standards and quality control samples were prepared by spotting 50 mL of dolutegravir-spiked whole blood on each circle of DBS cards. Three spots (two 6-mm punches/spot) were extracted with methanol. Chromatographic separation was achieved with gradient elution of acetonitrile/potassium phosphate monobasic buffer (pH 5) on a reverse-phase C18 column (flow rate, 1 mL/min) using pioglitazone as the internal standard. UV detection was performed at 260 nm. In the clinical pharmacokinetic study, DBS from finger prick was collected from participants (n = 10) at 8 time points over 12 hours postdosing, with paired plasma at 1 and 12 hours. The method was used to quantify dolutegravir, estimating pharmacokinetic parameters. Agreement between DBS and plasma concentrations was evaluated using linearity and Bland-Altman plots. Results:The method was validated over the concentration range of 0.4-10 mcg/mL, accuracy was 102.4%-114.8%, and precision was 3.4%-14.7%. The mean recovery was 42.3% (%CV: 8.3). The mean (6SD) dolutegravir concentration in DBS was 37.5% (63.8%) lower than that in the plasma. DBS-derived and measured plasma concentrations showed strong correlation with linearity (R 2 = 0.9804) and Bland-Altman plots. Means (%CV) of area under curve, C max , and C 24 from the DBS-derived plasma concentration were 37.8 (23.2) mcg$h/mL, 2.7 (24.7) mcg/mL, and 1.34 (31.6) mcg/mL, respectively. Conclusions:The application of this simple, accurate, and precise method will expand opportunities for clinical assessment of dolutegravir in resource-limited settings.

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The promise of paediatric dolutegravir

Cited by 12 publications

References 7 publications

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

Age-specific associations with dental caries in HIV-infected, exposed but uninfected and HIV-unexposed uninfected children in Nigeria

Achieving Antiretroviral Therapy Uptake and Viral Suppression Among Children and Adolescents Living With HIV in the UNAIDS 90-90-90 Era Across Six Countries in Eastern and Southern Africa—Lessons From the BIPAI Network

Validation and Clinical Application of a Liquid Chromatography–Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots

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