Citation: Ismael, N.; Wilkinson, E.; Mahumane, I.; Gemusse, H.; Giandhari, J.; Bauhofer, A.; Vubil, A.; Mambo, P.; Singh, L.; Mabunda, N.; et al. Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018. Viruses 2022, 14, 1992. https://doi.org/10.3390/ v14091992 Academic Editor: Orna Mor Received: 29 July 2022 Accepted: 5 September 2022 Published: 9 September 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). viruses Article Molecular Epidemiology and Trends in HIV-1 Transmitted Drug Resistance in Mozambique 1999–2018 Nalia Ismael 1,2, *, Eduan Wilkinson 3 , Isabel Mahumane 1 , Hernane Gemusse 1 , Jennifer Giandhari 4 , Adilson Bauhofer 1 , Adolfo Vubil 1 , Pirolita Mambo 1 , Lavanya Singh 4 ,Nédio Mabunda 1 , Dulce Bila 5 , Susan Engelbrecht 2 , Eduardo Gudo 1 , Richard Lessells 4 and Túlio de Oliveira 3, * 1 Instituto Nacional de Saúde (INS), Estrada Nacional N1, Marracuene 3943, Mozambique 2 Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa 3 Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch 7602, South Africa 4 KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4000, South Africa 5 Elizabeth Glaser Pediatric AIDS Foundation in Mozambique, Avenida Agostinho Neto, Maputo 620, Mozambique * Correspondence: nalia.ismael@ins.gov.mz (N.I.); tulio@sun.ac.za (T.d.O.) Abstract: HIV drug resistance (HIVDR) can become a public health concern, especially in low- and middle-income countries where genotypic testing for people initiating antiretroviral therapy (ART) is not available. For first-line regimens to remain effective, levels of transmitted drug resistance (TDR) need to be monitored over time. To determine the temporal trends of TDR in Mozambique, a search for studies in PubMed and sequences in GenBank was performed. Only studies covering the pol region that described HIVDR and genetic diversity from treatment naïve patients were included. A dataset from seven published studies and one novel unpublished study conducted between 1999 and 2018 were included. The Calibrated Population Resistance tool (CPR) and REGA HIV-1 Subtyping Tool version 3 for sequences pooled by sampling year were used to determine resistance mutations and subtypes, respectively. The prevalence of HIVDR amongst treatment-naïve individuals increased over time, reaching 14.4% in 2018. The increase was most prominent for non-nucleoside reverse transcriptase inhibitors (NNRTIs), reaching 12.7% in 2018. Subtype C was predominant in all regions, but a higher genetic variability (19% non-subtype C) was observed in the north region of Mozambique. These findings confirm a higher diversity of HIV in the north of the country and an increased prevalence of NNRTI resistance among treatment naïve individuals over time. Keywords: transmitted; drug; resistance; HIV; molecular epidemiology; Mozambique; mutations; genetic diversity; treatment naïve; temporal trend 1. Introduction In response to the HIV epidemic, antiretroviral treatment (ART) roll out has risen dramatically, with 28.2 million individuals on treatment by 2021 worldwide [1]. Although ART has substantially reduced HIV related morbidity, mortality, and transmission, HIV Drug Resistance (HIVDR) can become a problem, particularly in low- and middle-income countries (LMICs) where genotyping testing is not readily available [2,3]. Among ART naïve individuals, drug resistance may occur through Transmitted Drug Resistance (TDR) or Pretreatment HIV Drug Resistance (PDR) which may compromise the success of future first line regimens [4]. TDR occurs when an uninfected person naïve to antiretrovirals (ARVs) is infected with a resistant virus and PDR defined as resistance being detected among people initiating treatment or reinitiating first-line regimen after being exposed to ARVs [5]. Viruses 2022, 14, 1992. https://doi.org/10.3390/v14091992 https://www.mdpi.com/journal/viruses