Antiretroviral therapy (ART) has successfully reduced human immunodeficiency virus (HIV) morbi-mortality worldwide, and transmission to third parties lowering population viral loads, thereby, interrupting new infections [1]. ART is mostly effective; however, some people living with HIV (PLHIV) experience treatment non-response due to virological failure caused by ART resistance [2]. Resistance is classified into transmitted resistance to antiretroviral drugs (TDR), acquired resistance and pretreatment resistance. TDR occurs in PLHIV who have not previously received ART (treatment-naïve), and who are infected with a viral strain already carrying resistance-associated mutations. Acquired resistance occurs in patients on ART, mainly due to poor adherence to drug therapy, and pretreatment resistance refers to drug-resistant virus detected in ART–naive individuals or individuals with previous ART exposure initiating or reinitiating first-line ART [3], [4].

Globally, TDR prevalence has increased recently and varies across communities [3], [5]. In high-income countries, 12–24 % of ART-naïve individuals exhibit mutations conferring resistance to at least one antiretroviral drug [6], mainly to the non-nucleoside reverse transcriptase inhibitors (NNRTIs) family [7]. The same trend has been observed in countries of Latin America, the Caribbean, and the Southern Cone [5], [8], with most low- and middle-income countries exhibiting a NNRTIs resistance over 10 % [4], [5], [8]. Currently, transmitted resistance to protease inhibitors (PIs) is less common and to integrase strand transfer inhibitors (INSTIs) very rare [9], fluctuating between 0 % and 4 %. While global INSTIs resistance remains low, it holds significant relevance as cornerstone of first-line ART worldwide. Consequently, integrating integrase genotyping into TDR surveillance is crucial, considering the potential for increasing prevalence over time.

Chile experienced a rise in global TDR prevalence with 2.5 % of PLHIV exhibiting high/intermediate resistance mutations between years 2000–2005 [10] and 10.45 % between 2014 and 2018 [11]. Locally, NNRTIs presented the highest TDR percentage with 10.1 % cases sharing high/intermediate resistance mutations between 2000 and 2005 [10], 4.1 % between 2006 and 2008 [12], and 9 % between 2014 and 2018 [11]. The TDR percentage for the nucleoside reverse transcriptase inhibitors (NRTIs) family was 2.5 % between 2000 and 2005 [10] and 1.8 % between 2014 and 2018 [11]. For the PIs family, TDR was 1.3 % between 2006 and 2008 [12] and 0.45 % between 2014 and 2018 [11]. As for INSTIs, a small study in 2023 found 8 % TDR for first-generation INSTIs in 50 PLHIV [13].

In 2008, international experts recommended viral genotyping prior ART initiation when TDR prevalence is ≥ 10 % nationwide [14]. This practice improves PLHIV prognosis and life expectancy, and reduces long-term costs [15], [16]. Nonetheless, it is not the standard of care in low- and middle-income countries [17], and therefore, in several countries - including Chile - PLHIV initiate ART empirically based on clinical guidelines recommendations.

Currently, global TDR prevalence is increasing worldwide [4], and updated data for Chile, is lacking. Thus, this study aimed to determine the current TDR prevalence, including INSTIs, and identify epidemiological risk factors associated with TDR, to determine the necessity of implementing genotyping studies in ART-naïve PLHIV.