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Background: The WHO-recommended first-line antiretroviral therapy (ART) as a fixed dose combination (FDC) of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) with lamivudine (3TC) or emtricitabine (FTC) has been preferred in the large scale unprecedented ART roll out in Southern Africa. Models and recent reports suggest that pre-ART HIV drug resistance (PDR) is increasing with high treatment coverage., Method: We therefore investigated PDR and any local transmission clusters in a setting where high treatment coverage was further enhanced by universal test and treat (UTT). Surveillance drug resistance mutations (SDRMs) were identified with an in-house PCR and population sequencing method and calibrated population resistance (CPR) tool., Results: Of 60 patients, six (10%) had an SDRM mutation: five (8.3%) had nonnucleoside reverse transcriptase (NNRT) mutations, one had an nucleos(t)ide reverse transcriptase inhibitor mutation and none had protease inhibitor (PI) mutations. Phylogenetic analysis revealed no large transmission clusters., Conclusion: An increase to the current moderate PDR levels and the better tolerability and durability, may support a recent drive to avail FDC integrase strand transfer inhibitor (ISTI)-based regimens as the new preferred first-line ART in the Southern African region for individual benefit and to contribute to limiting transmission of infection and drug resistant virus.