11 Dec, 2020
Pablo Rojo, and Anna Turkova – members of Penta ID network have provided some rationale, and highlighted some challenges related to including adolescents in HIV clinical phase 3 trials of antiretroviral drugs in their co-authored commentary titled, “The HIV drug optimisation agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV” in the Journal of the International AIDS Society.
Most clinical trials for new antiretroviral drugs (ARVs) are conducted among narrowly defined adult populations, and only after safety and efficacy have been clearly shown in adults do trials move to include HIV-positive children and adolescents, significantly delaying the availability of ARVs and/or optimised combinations for use among these groups.
This approach is also applied to pregnant or breast-feeding women, and to women of reproductive age who are not receiving contraception.
Not including adolescents in new drug development trials, simplification trials or HIV treatment failure studies will continue to widen the existing antiretroviral therapy knowledge gap and further disadvantage this population.
The Paediatric Antiretroviral Working Group led by the World Health Organization (WHO), has proposed optimising research approaches for children and adolescents to speed-up the availability of antiretroviral drugs (ARVs) and formulations for these groups.
Penta led study, ODYSSEY trial already evaluated the use of the adult dolutegravir tablet (50 mg) not only in adolescents, but also in children weighing 20 to less than 40 kg. The results showed that the adult tablets achieved appropriate absorption, distribution, metabolism, and excretion with no safety signal, allowing practical dosing and rapid access to dolutegravir.
Furthermore, adult trials for tuberculosis and cancer treatment as well as ADVANCE, a recent clinical trial that enrolled HIV-positive participants aged 12 years and below, have shown the feasibility of including adolescents in adult clinical trials.
Although conducting clinical trials among adolescents present special challenges such as recruiting them into clinical trials, retaining them in treatment and follow-up, gaining their consent, and dealing with cultural beliefs related to contraception, these challenges can be addressed to obtain high-quality trial results.
Currently, Penta Foundation is supporting the creation of Youth Trial Boards in Uganda, Zimbabwe, South Africa, and United Kingdom to develop a youth-centred approach for meaningful involvement of young patients in clinical trials and studies.
The authors hint coordinating research efforts with key stakeholders and sharing experiences on how to overcome perceived and real difficulties could help promote clinical trials among adolescents.