The anti-HIV drug Dolutegravir improves outcomes for children with HIV infection when given in a 3-drug anti-HIV combination. These results come from the ODYSSEY trial which was presented yesterday at the Conference on Retroviruses and Opportunistic Infections.
Dolutegravir has a number of potential advantages, including:
- Few drug-to-drug interactions, making it easier to use when treating people who need treatment for other conditions such as tuberculosis
- High potency at a low milligram dose, meaning tablets can be small
- High genetic barrier to resistance
- Low cost
Trials of dolutegravir in combination treatments in adults with HIV have shown that it is as good as or better than other drugs. ODYSSEY is the first trial to look at whether treatment combinations based on dolutegravir are effective and safe for children living with HIV. Children who joined the trial were randomly allocated to receive either the current standard treatment combination, or one that included dolutegravir. The ODYSSEY trial had two parts: ODYSSEY A was for children who were on first-line treatment. ODYSSEY B was for children whose previous treatment had stopped working and were now on second-line treatment.
The results presented yesterday are from over 700 children in ODYSSEY who weighed at least 14kg, and were aged between 3 and 17 years. Children were followed up for at least 96 weeks.
ODYSSEY found that dolutegravir-based HIV treatment combinations were superior to standard-of-care regimens in terms of preventing treatment failure for children living with HIV who weighed at least 14kg. Children in the dolutegravir arm were less likely to experience treatment failure than those on standard treatment combinations. An estimated 14% of children in the dolutegravir arm had experienced treatment failure by 96 weeks, compared to 22% in the standard treatment combination arm.
The ODYSSEY results were consistent with the same benefit of doultegravir-based ART in children starting first or second line ART. This was true at 48, 96 and 144 weeks. We also looked at other sub-groups including by age, weight or ART backbone and results suggested that all sub-groups were likely to benefit from dolutegravir-based ART.
Side-effect data from ODYSSEY were reassuring. Overall, there was no difference in the rate of side-effects between the arms. In particular excessive weight gain was not seen with dolutegravir (as observed in some adult trials) and blood lipid values were lower than in the control arms.
These results support the current World Health Organisation treatment guidelines, which recommend dolutegravir-based combinations for treating children living with HIV for whom there is an approved dolutegravir dosing.
Data from ODYSSEY on the efficacy and safety of dolutegravir-based ART for children weighing less than 14kg are still being collected and will be released later this year.
ODYSSEY has already had an impact, with simplified dosing data from the trial contributing to the licensing of using adult dolutegravir tablets for children weighing over 20kgs, and approval of 5mg tablets for younger children. ODYSSEY has also contributed data for the regulatory approval of a generic fixed-dose combination tablet suitable for children containing the drugs abacavir and 3TC in South Africa.
Overall, all these contributions from ODYSSEY are ensuring that children are not left behind and receive the best possible treatment alongside adults.
The ODYSSEY trial was sponsored by the Penta Foundation, and coordinated by the MRC Clinical Trials Unit at UCL, as well as INSERM, PHPT and HIV-NAT-. 88% of children in this global trial were enrolled from Africa. It was funded by ViiV Healthcare and the PENTA Foundation. It took place in Uganda, Zimbabwe, South Africa, Thailand, and participating Penta centres in Germany, UK, Portugal, Spain.