Introduction Objectives: The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from 5% to 5%–15% in the past decade.

Methods Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario.

Results Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120–34 600 cases) of TDR and 55 180 cases (95% CI: 40540–65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%–24%) and ADR of 18% (95% CI: 15%–20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%–31% of TDR (2260–5860 cases), 25%–59% of ADR (9620–22 650 cases), 2%–6% of HIV-related deaths (360–880 cases) and 19270–51400 DALYs during 2015–30. The 30% coverage of VL monitoring is estimated to cost US$4848–5154 per DALY averted. The projected additional cost for implementing this strategy is US$105–268 million over 2015–30.

Conclusion Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds.