The promise of paediatric dolutegravir

In 2019, fewer than 55% of the estimated 1.8 million children living with HIV received life-saving antiretroviral therapy. Children in low- and middle-income countries continue to have limited access to optimal paediatric antiretroviral therapy, and viral load suppression rates among children remain unacceptably low. Since 2018, the World Health Organization has recommended the use of dolutegravir as part of the preferred first-line antiretroviral therapy regimen for all people living with HIV. However, to date, dolutegravir has only been available in low- and middle-income countries as a 50 mg, film-coated tablet, which can only be used by children who weigh at least 20 kg. In June 2020, the United States Food and Drug Administration approved a dispersible, 5 mg formulation of dolutegravir for use in infants and children living with HIV, and in November 2020, a paediatric dolutegravir 10 mg scored dispersible tablet formulation also received tentative US FDA approval. The introduction of a dolutegravir dispersible tablet is a significant advance in optimal treatment for children living with HIV. Based on data extrapolated from studies in adults, dolutegravir's efficacy is superior to both protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Introduction of dolutegravir directly addresses pre-treatment drug resistance among children living with HIV, as well as acquired drug resistance after failed non-nucleoside reverse transcriptase inhibitor- or protease inhibitor-based regimens. Additionally, due to a high genetic barrier to resistance, dolutegravir can be used along with an optimized NRTI backbone as an anchor drug throughout childhood and adulthood. Paediatric dolutegravir also comes in a convenient, once-daily, dispersible tablet formulation that can be dissolved and administered alongside dispersible formulations of ABC/3TC. This allows for greater convenience than twice-daily LPV/r and reduces pill burden. In addition, paediatric dolutegravir overcomes other disadvantages of LPV/r formulations, including the need for additional training to ensure appropriate adherence, poor palatability, and the inability to cut, crush, chew, or dissolve the tablet. The paediatric dolutegravir 10 mg scored dispersible tablet formulation has the potential to reduce implementation barriers associated with multi-month dispensing of antiretroviral therapy to children. With DTG10, caregivers will be able to confidently carry and safely store a less bulky, longer lasting supply of paediatric antiretroviral therapy. Paediatric dolutegravir is also favourable from a manufacturing standpoint, with challenges with LPV/r production occurring due to limited use of LPV/r in adults and limited manufacturers of paediatric LPV/r formulations. Since dolutegravir has been used in first-line adult antiretroviral therapy regimens since 2016, the active pharmaceutical ingredient is more readily available. Another important paediatric dolutegravir advantage is cost savings. Compared to LPV/r formulations, paediatric programmes can anticipate significant savings in both product and shipping costs. The estimated yearly cost savings of changing a child from LPV/r to DTG10 ranges from $90 to $1,200 USD per child, depending on the LPV/r formulation and dosing weight band. To adequately prepare for the rapid transition to paediatric dolutegravir, the following is recommended: national HIV treatment guidelines should clearly state that DTG-based antiretroviral therapy is the preferred first-line and second-line treatment for all people living with HIV, including children who meet the minimum age and weight thresholds for paediatric dolutegravir. Concurrent to revising national guidelines, countries should prepare for product registration with the national medicines regulatory authority, commodity procurement, and decentralized distribution while implementing appropriate pharmacovigilance measures, training facility and community cadres, and developing/disseminating context-specific information, education, and communication materials for healthcare workers and caregivers.