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Dolutegravir (Tivicay)-based antiretroviral therapy in children with HIV infection was superior to efavirenz-based standard of care in the first-line setting in a prospective trial, researchers reported.

In her presentation at the , Anna Turkova, MD, of University College London, added that in the second-line setting, it appears dolutegravir-based treatment is at least non-inferior to current treatment regimens.

Reporting for the team, she said the international, multicenter, randomized 96-week trials had 47 virologic failure events (14%) among children on dolutegravir compared with 75 (22%) among children on efavirenz, a difference that for this primary endpoint of the trial reached statistical significance (P=0.004).

When analyzed by first therapy, there were 15 virologic failures (10%) for dolutegravir-based therapy and 34 virologic breakthroughs (23%) among the children assigned to standard of care (P=0.003), Turkova said.

And in the second-line setting, 32 virologic failures occurred with dolutegravir (17%) and 41 virologic breakthroughs occurred with standard of care (21%), which did not reach statistical significance for superiority (P=0.22), but fell within the pre-specified margins for non-inferiority, she said.

While most of the children in the study were recruited from South Africa, Uganda, and Zimbabwe in Africa, 9% were from Thailand, and 4% were from the European nations of the U.K., as well as Germany, Spain, and Portugal.

Turkova told 番茄社区app at a virtual press conference that the study should be generalizable to the entire world, since the trialists stratified patients by geographical area, and "about 4% of the patients were from Europe, and there were no differences among the groups by geographic region."

Overall, 707 children who weighed more than 14 kg (about 31 lbs) and who were younger than 18 years were enrolled in both arms of the study.

For ODYSSEY A, a total of 311 children were entered into the first-line setting, with 154 randomly assigned to dolutegravir plus two nucleoside reverse transcriptase inhibitors. The other 157 participants were assigned to standard-of-care treatment -- i.e., efavirenz plus a doublet of nucleoside reverse transcriptase inhibitors.

In ODYSSEY B, the second-line study, 196 children were assigned to dolutegravir-based therapy and 200 were assigned to standard of care. The most common second-line treatment was boosted lopinavir, taken by 75% of the children, while the others were on atazanavir-based therapy.

Across the studies, the median age of the children enrolled was 12.2 years (range of 2.9 years to 18 years). About 49% of the cohort were girls, and 22% of the cohort were found to have baseline CD4-positive cell counts less than 200 cells/mm³.

When the outcomes were analyzed on a per-protocol basis, the outcomes were similar for both ODYSSEY A and ODYSSEY B, Turkova said in her oral presentation.

She said the study participants were stratified by age, weight, sex, and geographic location, but none of those factors showed any differences from the overall trial results.

She noted that at 44 weeks, dolutegravir was superior to standard of care in both trial arms, but by week 96, dolutegravir was non-inferior to standard of care in the second-line setting. That result has persisted through week 144, Turkova reported.

Two children in the dolutegravir arms died during the study, and there were three deaths in the standard-of-care arms across both studies.

Overall, the CD4-positive cell counts in both arms rose about 200 cells/mm³, with a nonsignificant 35 CD4-positive cell count edge in the dolutegravir arms (P=0.14), Turkova said.

An ongoing trial is now examining outcomes in children with a body weight lower than 14 kg, she noted.

Commenting on the study at the press conference, Sharon Hillier, PhD, of the University of Pittsburgh School of Medicine, noted that the ODYSSEY trials and others presented at the conference appeared to underscore the effectiveness of dolutegravir, which has had a bumpy rollout as the treatment of choice in resource-limited settings with a high prevalence of HIV infection.

"It has been amazing watching the increasing body of evidence in support of the dolutegravir -- integrase inhibitors -- regimens," Hillier told 番茄社区app. "We are also understanding efavirenz and its limitations in treatment."

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