Predicted dolutegravir resistance in South Africa, 2020–35
Dolutegravir is now the backbone of HIV treatment worldwide due to its high barrier to resistance and good tolerability. However, delays in detecting treatment failure and limited access to resistance testing may allow resistance to accumulate.
Loosli et al used the MARISA model, a large-scale epidemic and resistance evolution model, to project dolutegravir resistance trends in South Africa from 2020 to 2035.
The model predicted that by 2035 around 7 million people will be on dolutegravir-based therapy, with 93% virally suppressed. Among those with virological failure, acquired dolutegravir resistance was projected to rise from 19% in 2023 to 42% in 2035. Transmitted resistance is also expected to increase, from 0.1% in 2023 to 5% in 2035, potentially exceeding the WHO’s 10% threshold for pre-treatment resistance in worst-case scenarios.
Mitigation strategies—such as rapid switching to protease inhibitor–based therapy or genotypic-resistance–guided treatment adjustment—could substantially curb resistance, reducing acquired resistance to below 10% and transmitted resistance to around 1–2% by 2035.
In summary, although dolutegravir remains highly effective, its long-term success in South Africa will depend on earlier detection of treatment failure and faster regimen switching. Strengthened viral load monitoring and wider access to resistance testing will be critical to preserve dolutegravir’s effectiveness at the population level.