Background HIV drug resistance (HIVDR) testing was included in the 2017 South African national HIV household survey. We describe the prevalence of HIVDR by drug class, age, sex and antiretroviral drugs (ARV) status. Methods Dried blood were spots tested for HIV, with Viral load (VL), exposure to ARVs and HIVDR testing among those HIV positive. HIVDR testing was conducted on samples with VL ≥1000 copies/ml using Next Generation Sequencing. Weighted percentages of HIVDR are reported. Results 697/1,105 (63%) of HIV positive samples were sequenced. HIVDR was detected in samples from 200 respondents (27.4% (95% confidence interval (CI) 22.8–32.6)). Among these 130 (18.9% (95% CI 14.8–23.8)), had resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) only, 63 (7.8% (95% CI 5.6–10.9)) resistance to NNRTIs and nucleoside reverse transcriptase inhibitors, and 3 (0.5% (95% CI 0.1–2.1)) resistance to protease inhibitors. Sixty-five (55.7% (95% CI 42.6–67.9) of ARV-positive samples had HIVDR compared to 112 (22.8% (95% CI 17.7–28.7)), in ARV-negative samples. HIVDR was found in 75.6% (95% CI 59.2–87.3), n = 27, samples from respondents who reported ARV use but tested ARV-negative, and in 15.3% (95% CI 6.3–32.8), n = 7, respondents who reported no ARV use and tested ARV-negative. There were no significant age and sex differences in HIVDR. Conclusion 27% of virally unsuppressed respondents had HIVDR, increasing to 75% among those who had discontinued ARV. Our findings support strengthening first-line ARV regimens by including drugs with a higher resistance barrier and treatment adherence strategies, and close monitoring of HIVDR.

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