HIV-1 Pretreatment and Acquired Antiretroviral Drug Resistance before tenofovir/ /lamivudine /dolutegravir (TLD) roll-out in Mozambique Running title: Pretreatment and Acquired HIV Drug Resistance in Mozambique

Abstract Introduction The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. Included in the WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy is HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. Methods We carried out a cross-sectional study between March 2017 and December 2019. HIV-1 infected adults (re)initiating or receiving first-line treatment for 9–15 months were included in 25 health facilities across all 11 provinces in Mozambique. HIV drug resistance (HIVDR) was assessed on dried blood spot (DBS) samples with a viral load ≥ 1000 copies/mL. Resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance 8.1. Results A total of 828 participants were enrolled (419 new initiators and 409 ART experienced), the majority were females (58.4% new initiators and 62.6% ART-experienced) with a median age of 36 and 32 years for ART initiators and ART experienced, respectively. Of the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 17.4% and 1.4% of the participants, respectively. Among the patients on first-line treatment, 81.2% (n = 332) had suppressed viral loads (VL) and the remaining 18.8% (n = 77) had unsuppressed VL. Of these 90% (n = 70) were successfully sequenced and 56.6% (30/70) (95% CI 43–70) showed high-level resistance for NNRTI. Mutations Acquired drug resistance (ADR) for both NRTI and NNRTI were identified in 24.5% (13, 95% CI: 13–36) among the treatment-experienced participants. Conclusion High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir but high levels of NRTI resistance in highly treatment-experienced individuals still requires attention when transitioning to new regimens. Moreover, the study underlines the need for robust routine VL testing and HIVDR surveillance to improve treatment management strategies.