South Africa’s antiretroviral treatment (ART) programme is the largest globally with >4 million HIV-infected persons receiving standardized treatment regimens. Monitoring levels of HIV drug resistance (HIVDR) is a priority activity for the country. HIVDR testing was included for the first time in the 5th national HIV household survey conducted in 2017.
Multi-stage stratified cross-sectional random sampling was used to select households for participation nationally. Dried blood spots were tested to determine HIV status, estimated recency of infection, exposure to antiretroviral drugs (ARVs), and HIVDR in addition to behavioral data from all household members who agreed to participate. HIVDR testing was conducted on HIV-positive samples with viral load ≥1000 copies/ml using next generation sequencing methodologies.
Of 1107 HIV positive samples from virally unsuppressed participants, 697 (63%) were successfully amplified by polymerase chain reaction and sequenced. Drug resistant mutations (DRM) were identified in 27.4% (95% CI 22.8-32.6) of samples: 18.9%(95% CI 14.8-23.8) had resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) only, 7.8% (95% CI 5.6-10.9) had dual resistance to NNRTIs and nucleoside reverse transcriptase inhibitors(NRTIs), and 0.5% (95% CI 0.1-2.1) had resistance to second-line regimens that include protease inhibitors (PIs),NNRTIs, and NRTIs). Table 1 shows HIVDR by exposure to ARVs, sex, and age. NNRTI-only resistance was found in 14.3% ARV+ve and 20.0% ARV-ve samples (p=0.311), while dual NNRTI and NRTI resistance occurred in 40% ARV+ve and 2.1% ARV–ve samples (p< 0.001). Among those who were ARV-ve but self-reported daily ARV use (ARV defaulters; n=41), 75.6% had DRM; 56.4% with NNRTI-only resistance, 14.3% with dual NNRTI and NRTI resistance. There were no significant age and sex differences among either NNRTI-only resistant and dual NNRTI and NRTI resistant samples.
These findings demonstrate high proportions of DRM among virally unsuppressed HIV-infected persons in South Africa. While these results include treatment defaulters, potential pretreatment HIVDR levels are concerning. Programmatic implications include stronger adherence support to reduce ARV defaulting, and strengthened first line ART regimens by including integrase strand transfer inhibitors (INSTIs) as a part of first line treatment. These findings support the national transition to include Dolutegravir as part of first-line ART in South Africa.