How frequent is dolutegravir resistance?

Area of Science:

• Virology
• Infectious Diseases
• Public Health

Background:

• HIV remains a significant global health challenge, with antiretroviral drug supply disruptions posing mortality and transmission risks.
• Dolutegravir, an integrase strand transfer inhibitor, is crucial in combating HIV, known for its high resistance barrier in high-income settings.
• Emerging reports of dolutegravir resistance in resource-limited settings necessitate an evaluation of its efficacy in these populations.

Purpose of the Study:

• To review recent literature and conference communications on acquired drug resistance to dolutegravir in low- and middle-income countries.
• To assess the prevalence and characteristics of dolutegravir resistance in resource-limited settings.
• To identify factors associated with dolutegravir resistance and inform strategies for optimizing HIV treatment.

Main Methods:

• Systematic literature search of published studies and conference abstracts.
• Focus on acquired drug resistance to dolutegravir.
• Inclusion of data from low- and middle-income countries.

Main Results:

• Dolutegravir resistance primarily emerged in individuals with unsuppressed viral loads and adherence challenges.
• Population-level resistance rates remained below 1% despite structural barriers.
• The R263K substitution was common, and re-suppression with dolutegravir was often possible.
• Minor programmatic adjustments could enhance outcomes.

Conclusions:

• Dolutegravir maintains a high barrier to resistance in low-income countries, even with adherence issues.
• Continued emphasis on treatment adherence support is vital.
• Maintaining robust antiretroviral drug supply chains is critical for sustained HIV treatment success.