Pretreatment HIV drug resistance spread within transmission clusters in Mexico City

Background: Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. Objectives: To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. Patients and methods: HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (>= 20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a >= 2% threshold to include low-frequency variants. Results: Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P<0.001). Clustering individuals were younger [adjusted OR (aOR) per year=0.96, 95% CI 0.95-0.97, P<0.001] and less likely to include women (aOR=0.46, 95% CI 0.28-0.75, P=0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR=0.93, 95% CI 0.88-0.98, P=0.003). Conclusions: Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.