Pharmacokinetics, Safety, Tolerability and Antiviral Activity of Dolutegravir Dispersible Tablets in Infants and Children with HIV-1: Results of the IMPAACT P1093 Study, a Phase I/II Open-Label Trial

Ruel, Theodore; Acosta, Edward P.; Liu, Jessica P.; Gray, Kathryn P.; George, Kathleen; Montañez, Nicole; Popson, Stephanie; Buchanan, Ann M.; Bartlett, Mattie; Dayton, Dale; Anthony, Patricia; Brothers, Cynthia H.; Vavro, Cynthia; Singh, Rajendra; Koech, Lucy; Vhembo, Tichaona; Hazra, Rohan; Townley, Ellen; Wiznia, Andrew; Team, Impaact P Protocol

doi:10.2139/ssrn.3954096

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Though, those who were ART naïve when starting DTG were more likely to achieve viral suppression compared to those who were previously suppressed prior to DTG, though not statistically significant. The findings are consistent with the study done in nine countries which involved Africa, Asia, North America, and South America [25].…”

Section: Socio-demographic and Clinical Characteristics Among The Calhivsupporting

confidence: 92%

Hiv Viral Suppression and Associated Factors Among Children and Adolescents on a Dolutegravir (Dtg) Based Antiretroviral Regimen in Tanzania Mainland

Maghembe,

Boer,

Marikias

et al. 2023

Preprint

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Introduction Antiretroviral therapy (ART) reduces morbidity and mortality due to human immunodeficiency virus (HIV) infection. The complexity and time-consuming processes, particularly in drug approvals, have contributed to a major challenge to the ongoing success of antiretroviral treatment programs among children and adolescents. In 2019, Tanzania adopted DTG as a first-, second-line and third-line treatment for CALHIV on ART after being approved by the World Health Organisation (WHO). DTG treatment has highly potent antiviral activity, a high genetic barrier to resistance, and a high safety profile. This study aimed to determine HIV viral suppression and associated factors among CALHIV on DTG-based ART in Tanzania Mainland. Methods This was a retrospective cohort analysis among children and adolescents living with HIV who were on a DTG-based regimen in Tanzania Mainland between 2019 and 2021. The study utilized routinely collected data from Tanzania Care and Treatment Centres (CTC). We analysed data using STATA version 15 software. We calculated the prevalence of viral suppression by taking the number of children and adolescents with <1000 copies/ml overall study participants. A mixed effect generalized linear model with Poisson distribution and log link function with robust estimator determined the factors associated with HIV viral suppression on a DTG-based regimen. Results A total of 63,453 CALHIV on a DTG-based regimen were analysed. The proportion of viral suppression was 91.64%. Overall, 66.19% of previously unsuppressed individuals became suppressed and 88.45% of previously suppressed remained suppressed. Factors leading to lower chances of viral suppression were age 10-14 years (aRR: 0.98; 95%CI: 0.97-0.99), previously unsuppressed prior to starting DTG (aRR: 0.92; 95%CI: 0.91-0.93), duration on ART more than 24 months (aRR: 0.96; 95%CI: 0.94-0.97), not retained in care (aRR: 0.83; 95% CI: 0.77-0.89), severe malnutrition (aRR:0.77; 95%CI: 0.69-0.94) and coastal zone (aRR: 0.98; 95% CI: 0.96-0.99), while those in WHO stage I (aRR: 1.03; 95%CI: 1.01-1.04) and ever received a multi-month prescription (aRR: 1.25; 95% CI: 1.23-1.28) had a higher chance of viral suppression. Conclusions The findings support the broad use of DTG-based regimens for eligible CALHIV. Especially those in baseline WHO stage I and those who received the multi-month prescriptions were more likely to achieve viral load suppression. Programs should improve strategies to maintain CALHIV retention in care with interventions like the promotion of teen clubs and teams.

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Section: Socio-demographic and Clinical Characteristics Among The Calhivsupporting

confidence: 92%

Hiv Viral Suppression and Associated Factors Among Children and Adolescents on a Dolutegravir (Dtg) Based Antiretroviral Regimen in Tanzania Mainland

Maghembe,

Boer,

Marikias

et al. 2023

Preprint

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“…Based on a dosing sub-study of the Odyssey trial supporting the use of the DTG 50 mg tablet in children over 20 kg, 9 South Africa's 2019 ART guidelines expanded DTG access to children from 20 kg, 3 which greatly improved treatment in these children. Further Odyssey sub-studies and the P1093 study also showed good data for DTG in children from 3 kg to 20 kg; 6,10,11 however, for infants and children weighing less than 20 kg, access to DTG is dependent on availability of a new dispersible child-friendly formulation. First-line ART for infants and children < 20 kg has been a backbone of the protease inhibitor lopinavir/ritonavir and the two nucleoside-reverse-transcriptase inhibitors, abacavir and lamivudine.…”

mentioning

confidence: 98%

Paediatric antiretroviral update

Sorour¹,

Sipambo²,

Archary³

2023

South. Afr. j. HIV med.

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The rollout of paediatric dolutegravir and virological outcomes among children living with HIV in Mozambique

Meque,

Herrera,

Nhangave

et al. 2024

Southern African Journal of HIV Medicine

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Background: In 2022, Mozambique introduced Dolutegravir 10mg (pDTG), as part of paediatric antiretroviral therapy for children weighing 20 kg. Understanding real-world challenges during national rollout can strengthen health systems in resource-limited settings.Objectives: We described the transition rate to, and new initiation of, pDTG, viral load suppression (VLS) post-pDTG, and factors associated with VLS among children living with HIV.Method: We conducted a retrospective cohort study involving children aged 9 years and abstracted data from clinical sources. We used logistic regression to assess VLS and pDTG initiation predictors.Results: Of 1353 children, 1146 initiated pDTG; 196 (14.5%) had no recorded weight. Post-pDTG switch, 98.9% (950/961) of children maintained the same nucleoside reverse transcriptase inhibitor backbone. After initiating Abacavir/Lamivudine+pDTG, 834 (72.8%) children remained on the regimen, 156 (13.6%) switched off (majority to Dolutegravir 50mg), 22 (1.9%) had ≥ 2 anchor drug switches; 134 (11.7%) had no documented follow-up regimen. Factors associated with pDTG initiation or switch were younger age (adjusted odds ratio [AOR] = 0.71 [0.63–0.80]) and a recorded weight (AOR = 55.58 [33.88–91.18]). VLS among the 294 children with a viral load (VL) test after ≥ 5 months post-pDTG was 75.5% (n = 222/294). Pre-pDTG VLS rate among treatment-experienced children was 56.5% (n = 130/230). Factors associated with VLS were older age (AOR = 1.18 [1.03–1.34]) and previous VLS (AOR = 2.27 [1.27–4.06]).Conclusion: Most eligible children initiated pDTG per guidelines, improving post-pDTG VLS. Challenges included unexplained switches off pDTG after initiation, low VL coverage and inadequate documentation in clinic records.

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Pharmacokinetics, Safety, Tolerability and Antiviral Activity of Dolutegravir Dispersible Tablets in Infants and Children with HIV-1: Results of the IMPAACT P1093 Study, a Phase I/II Open-Label Trial

Cited by 3 publications

References 11 publications

Hiv Viral Suppression and Associated Factors Among Children and Adolescents on a Dolutegravir (Dtg) Based Antiretroviral Regimen in Tanzania Mainland

Hiv Viral Suppression and Associated Factors Among Children and Adolescents on a Dolutegravir (Dtg) Based Antiretroviral Regimen in Tanzania Mainland

Paediatric antiretroviral update

The rollout of paediatric dolutegravir and virological outcomes among children living with HIV in Mozambique

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