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Background Pre-treatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in low-/middle-income countries during the last decade. Objectives To estimate the prevalence of pre-treatment HIVDR and acquired HIVDR among persons living with HIV (PLHIV) on ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in Honduras. Patients and methods A nationwide cross-sectional survey with a two-stage cluster sampling was conducted from October 2016 to November 2017. Twenty-two of 54 total ART clinics representing >90% of the national cohort of adults on ART were included. HIVDR was assessed for protease and reverse transcriptase Sanger sequences using the Stanford HIVdb tool. Results A total of 729 PLHIV were enrolled; 26.3% (95% CI 20.1%–33.5%) ART initiators reported prior exposure to antiretrovirals. Pre-treatment HIVDR prevalence was 26.9% (95% CI 20.2%–34.9%) to any antiretroviral and 25.9% (19.2%–33.9%) to NNRTIs. NNRTI pre-treatment HIVDR was higher in ART initiators with prior exposure to antiretrovirals (P = 0.001). Viral load (VL) suppression rate was 89.7% (85.1%–93.0%) in ADR12 and 67.9% (61.7%–73.6%) in ADR48. ADR12 to any drug among PLHIV with VL ≥1000 copies/mL was 86.1% (48.9%–97.6%); 67.1% (37.4%–87.5%) had HIVDR to both NNRTIs and NRTIs, and 3.8% (0.5%–25.2%) to PIs. ADR48 was 92.0% (86.8%–95.3%) to any drug; 78.1% (66.6%–86.5%) to both NNRTIs and NRTIs, and 7.3% (1.8%–25.1%) to PIs. Conclusions The high prevalence of NNRTI pre-treatment HIVDR observed in Honduras warrants consideration of non-NNRTI-based first-line regimens for ART initiation. Programmatic improvements in HIVDR monitoring and adherence support may also be considered.

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