A secondary analysis of the ODYSSEY trial found that dolutegravir-based antiretroviral therapy may have led to significantly faster virologic suppression and lower virologic failure rates compared with standard-of-care regimens in pediatric and adolescent patients with humman immunodeficiency virus infections.
In the open-label, multicenter, randomized, non-inferiority ODYSSEY trial, published in The Lancet HIV, investigators evaluated virologic outcomes and resistance profiles up to 96 weeks in a cohort of 788 participants from 29 centers across seven countries.
The study was conducted in Germany, Spain, South Africa, Thailand, the United Kingdom, Uganda, and Zimbabwe. The participants, aged 28 days to 18 years, either initiated first-line antiretroviral therapy (ART) (ODYSSEY A) or switched to second-line therapy following a lack of treatment response (ODYSSEY B). Among the 788 participants, 391 of them received dolutegravir-based ART, whereas 397 of them received standard-of-care (SOC) regimens.
Virologic suppression occurred significantly earlier in the dolutegravir group (adjusted cause-specific hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.35–1.83, P < .0001). By week 96, virologic failure rates were lower in the dolutegravir group (13%) compared with in the SOC group (22%) (adjusted HR = 0.56, 95% CI = 0.40–0.79, P = .0011). In ODYSSEY A, failure was observed in 10% of the participants receiving dolutegravir vs 22% of those receiving SOC (adjusted HR = 0.39, 95% CI = 0.23–0.68, P = .0009). In ODYSSEY B, failure rates were 16% and 21%, respectively (adjusted HR = 0.73, 95% CI = 0.46–1.15, P = .17).
Dolutegravir was associated with a lower rate of emergent resistance in first-line therapy. By week 96, 1% (95% CI = 0–2) of those in the dolutegravir group developed resistance to at least one drug class compared with 20% (95% CI = 14–26) of those in the SOC group (P < .0001). In second-line therapy, emergent resistance to nucleoside reverse transcriptase inhibitors (NRTIs) was similar between groups (4% in the dolutegravir group vs 5% in the SOC group, P = .60). Emergent integrase strand-transfer inhibitor (INSTI) resistance occurred in 3% of the participants in both groups (P = .78).
"Dolutegravir is protective against emergent resistance to the anchor drug and NRTI backbone for [pediatric patients] starting first-line therapy," said lead study author Ellen White, PhD, of the MRC Clinical Trials Unit at the Institute of Clinical Trials and Methodology at the University College London, and her colleagues.
Among ODYSSEY B participants, those receiving dolutegravir with a zidovudine-based backbone had a higher risk of virologic failure compared with those receiving abacavir (HR = 2.22, 95% CI = 1.01–4.88, P = .048). Failure rates were similar among those receiving dolutegravir with tenofovir disoproxil fumarate vs abacavir (HR = 1.19, 95% CI = 0.50–2.83, P = .70).
The investigators emphasized the need for continued adherence support, noting that "30 of 51 [patients] in the dolutegravir group reached virologic resuppression without switching ART. This suggests that adherence interventions may be warranted before modifying treatment," the study authors emphasized.
These findings reinforced World Health Organization recommendations for dolutegravir-based ART in pediatric HIV. Future research may focus on long-term resistance trends and adherence strategies to optimize treatment outcomes.
The study was funded by the Penta Foundation, ViiV Healthcare, and the UK Medical Research Council with with no major conflicts of interest reported.
