National representative survey of pretreatment HIV drug resistance in Colombia: analysis of antiretroviral resistance-associated mutations using next-generation sequencing.

BACKGROUND

HIV pretreatment drug resistance (PDR) is an increasing global concern affecting transmitted resistance and first-line therapy effectiveness. Colombia lacks recent nationwide data on transmitted resistance. Although national guidelines recommend second-generation integrase strand transfer inhibitors (INSTIs) as preferred first-line options, efavirenz remains widely prescribed. This study estimated HIV PDR prevalence in Colombia to inform best practices for first-line antiretroviral therapy.

METHODS

We conducted a cross-sectional, nationally representative survey using next-generation sequencing of plasma samples from individuals initiating or reinitiating first-line antiretroviral treatment across Colombia's natural regions, stratified by national HIV prevalence data. Samples collected between 2021 and 2023 were analysed for drug resistance mutations (DRMs) following World Health Organization recommendations and interpreted using Stanford HIVdb v9.6.

RESULTS

A total of 483 participants were enrolled; 98.3% had HIV-1 subtype B, 94.3% were Colombian nationals, the median age was 32.5 years (standard deviation ± 10.8), 19.9% were female, and 27.5% had CD4 counts <200 cells/mm³. Median HIV-1 RNA was 54 754 copies/mL (interquartile range [IQR]: 15 685-166 000); 6.2% were treatment reinitiators. The wild-type virus was identified in 61.7%. Overall, PDR prevalence was 20.3% (95% confidence interval [CI] 16.8-24.2), driven mainly by non-nucleoside reverse transcriptase inhibitor resistance (NNRTI) (18.0%, 95% CI 14.7-21.7), with K103N as the most frequent DRM. INSTI DRMs were rare (2.1%).

CONCLUSIONS

This nationwide survey demonstrates alarmingly high NNRTI resistance but minimal INSTI resistance, underscoring the urgent need to phase out efavirenz-based regimens. Strengthening access to affordable second-generation-based therapies and enhancing prescriber education are critical to sustaining treatment efficacy and preventing further transmission of resistant HIV strains.