New results from the D3 (PENTA-21) trial, sponsored by Fondazione Penta ETS, add to the evidence that dolutegravir-based treatment remains a strong option for children living with HIV, even when the HIV virus had mutated and was resistant to other non dolutegravir-based medications. In the nested pharmacokinetic sub-study, which explored how the drugs moved through the body, children maintained high rates of viral suppression despite having previous resistance to other medications.
These findings, presented at the International Workshop on Pediatrics and HIV, are important because they look not only at whether treatment works, but also at how the virus behaves over time in children living with HIV who have already been treated before. This is especially important in these children because they may have older drug-resistance mutations hidden in latent viral DNA.
The D3 (PENTA-21) study followed children aged 2 to under 15 years who already had their HIV well controlled. Some children switched to dolutegravir plus lamivudine (DTG/3TC), while others stayed on dolutegravir plus two other HIV medicines.
Researchers then checked whether older resistance mutations in the virus affected how well the treatment worked. They looked at blood samples over time to see if the virus rebounded (multiplied again after being under control) and whether any new resistance appeared.
The results were reassuring. The HIV infection in most children remained suppressed through week 48, even if older resistance mutations were already present. This suggests that those older changes did not seem to weaken treatment in the short term.
One resistance-related finding was that some mutations detected in HIV DNA were likely the result of a natural virus editing process rather than true drug resistance, and these did not appear to affect treatment success.
Another finding was that the most common resistance mutation observed in the study may be associated with a higher risk of viral rebound. However, because only a small number of children experienced viral rebound by week 48, this association could not be confirmed with certainty. Results from the main study up to week 96 suggested that this risk may be present in both treatment groups (DTG/3TC and DTG plus two other HIV medicines) related to a very specific common resistance mutation.
Overall, resistance was uncommon in children who did experience viral rebound, and the two treatment groups looked broadly similar. This supports the encouraging message of DTG/3TC as a simpler treatment option for many children who are already doing well on HIV treatment, including in settings with fewer resources.