The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV.

INTRODUCTION: Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. DISCUSSION: The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high-quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side-effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV-positive adolescents. CONCLUSIONS: Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV-positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach.