DTG Resistance
As shown above, DTG offers high efficacy, good tolerability, and a strong genetic barrier to resistance, making it a cornerstone of current first-line treatment strategies, especially in high-prevalence regions like southern Africa.
However, while resistance to DTG remains relatively rare, emerging cases of DTG resistance pose a significant threat to recent progress in HIV control. In Lesotho, to assess the prevalence of DTG resistance, we analysed samples from VICONEL participants experiencing persistent or recurrent viremia while on DTG-based regimens. Among this subgroup, 9% were found to have intermediate to high-level resistance to DTG (21), underscoring the urgency of addressing this growing challenge.
In response, the VICONEL-resistance[JB1] project aims to deepen understanding and improve the clinical management of DTG resistance. Specifically, we are:
Identifying predictors of DTG resistance and developing validated eligibility criteria for genotypic resistance testing (GRT).
Assessing the impact of GRT-informed care on treatment outcomes among individuals at risk of DTG resistance:
a. In the overall at-risk population.
b. Among those with confirmed DTG resistance.
Quantifying the evolutionary dynamics of DTG resistance, including the accumulation of resistance-associated and compensatory mutations, and evaluating their phenotypic, clinical, and epidemiological relevance.
This research will inform HIV programs in high-burden settings on the value of targeted GRT in line with the World Health Organisation’s public health approach and address critical knowledge gaps around the emergence, progression, and clinical significance of DTG resistance. (https://data.snf.ch/grants/grant/10003309).
Implementation Network
To complement this scientific work, we are establishing an Implementation Network focused on HIV drug resistance in Lesotho. This initiative aims to:
Improve the accessibility and application of resistance data for healthcare providers, patients, and policymakers.
Develop a national HIV resistance database to support surveillance and case management.
Create training materials and deliver nationwide capacity-building for healthcare workers on the management of HIV drug resistance.
Launch a civil society information campaign to raise public awareness of HIV drug resistance.
Through these activities, we aim to strengthen local healthcare systems and empower communities to respond effectively to the challenges posed by emerging resistance, thereby improving long-term outcomes in HIV care. (https://data.snf.ch/grants/grant/229223)
[JB1]This is just a placeholder - but I think we do need a name
Ndovu study
Additionally, we are participating in the Ndovu study, a multi-country initiative investigating the optimal management strategies for individuals with DTG resistance. This collaboration allows us to contribute to a broader evidence base on how best to detect, monitor, and manage DTG resistance across diverse settings. Insights from the Ndovu study will be pivotal in shaping future guidelines and treatment policies to ensure sustained virologic suppression and preserve the long-term efficacy of DTG-based regimens. (https://clinicaltrials.gov/study/NCT06747507).
Funding: Gates Foundation
Leads: Dr Loice Achieng (…)
Lesotho leads: Irene Ayakaka (SolidarMed), Blaise Lukau (SolidarMed)