*Article* **HIV Pretreatment Drug Resistance Trends in Mexico City, 2017–2020**

**Claudia García-Morales 1, Daniela Tapia-Trejo 1, Margarita Matías-Florentino 1, Verónica Sonia Quiroz-Morales 1, Vanessa Dávila-Conn 1, Ángeles Beristain-Barreda 1, Miroslava Cárdenas-Sandoval 1, Manuel Becerril-Rodríguez 1, Patricia Iracheta-Hernández 2, Israel Macías-González 2, Rebecca García-Mendiola 3, Alejandro Guzmán-Carmona 3, Eduardo Zarza-Sánchez 1, Raúl Adrián Cruz 3, Andrea González-Rodríguez 2, Gustavo Reyes-Terán 4 and Santiago Ávila-Ríos 1,\***


Periférico Sur 4809, Colonia Arenal de Tepepan, Mexico City 14610, Mexico; gustavo.reyesteran@gmail.com **\***Correspondence:santiago.avila@cieni.org.mx;Tel.: +52-55-5666-7985(ext.133)

**Abstract:** In response to increasing pretreatment drug resistance (PDR), Mexico changed its national antiretroviral treatment (ART) policy, recommending and procuring second-generation integrase strand-transfer inhibitor (INSTI)-based regimens as preferred first-line options since 2019. We present a four-year observational study describing PDR trends across 2017–2020 at the largest HIV diagnosis and primary care center in Mexico City. A total of 6688 baseline protease-reverse transcriptase and 6709 integrase sequences were included. PDR to any drug class was 14.4% (95% CI, 13.6–15.3%). A significant increasing trend for efavirenz/nevirapine PDR was observed (10.3 to 13.6%, *p* = 0.02). No increase in PDR to second-generation INSTI was observed, remaining under 0.3% across the study period. PDR was strongly associated with prior exposure to ART (aOR: 2.9, 95% CI: 1.9–4.6, *p* < 0.0001). MSM had higher odds of PDR to efavirenz/nevirapine (aOR: 2.0, 95% CI: 1.0–3.7, *p* = 0.04), reflecting ongoing transmission of mutations such as K103NS and E138A. ART restarters showed higher representation of cisgender women and injectable drug users, higher age, and lower education level. PDR to dolutegravir/bictegravir remained low in Mexico City, although further surveillance is warranted given the short time of ART optimization. Our study identifies demographic characteristics of groups with higher risk of PDR and lost to follow-up, which may be useful to design differentiated interventions locally.

**Keywords:** HIV pretreatment drug resistance; HIV acquired drug resistance; Mexico City; Mexico
