The D3 clinical trial
toxicities, HIV-1 infected children and adolescents, fatigue
EVENT
ART has hugely improved life expectancy for individuals living with HIV. Current HIV treatment guidelines recommend ART regimens consisting of three antiretroviral drugs: two nucleoside/nucleotide analogue reverse-transcriptase inhibitors (NRTIs) as a backbone, combined with an integrase strand transfer inhibitor (INSTI) as the “anchor” drug. DTG is currently recommended as a preferred anchor drug for treatment of children and adolescents.Life-long ART is associated with challenges of treatment fatigue and long-term toxicities. Hence, research focus has shifted to investigating more tolerable and less toxic regimens that could improve the quality of life of patients, without compromising effectiveness.The D3 trial aims to compare DTG/3TC dual therapy in HIV-1 infected children and adolescents who are virologically suppressed on their ART regimen to DTG-based three-drug ART as the recommended preferred first-line treatment for children [The expected control event risk and loss to follow-up assumptions were chosen in order to be conservative given the literature, in particular since larger control event risks imply larger sample sizes, a high control event risk was selected. The BREATHER trial recruited young people aged 8–24 years (including 61% aged ≥ 13 years) and all participants were on efavirenz-based ART; in the control arm (where 3-drug ART was given daily) the risk of virological rebound was 11% by 96 weeks [However, there remain potential problems with the design: if the control event risk is lower than expected, then a 10% non-inferiority margin might be considered too large to conclude the non-inferiority of the 2-drug arm. For example, FDA guidance on HIV switch trials [