Abstract Body

Mathematical models suggest that high levels of transmitted drug resistance (TDR) could compromise ART programmes. We assessed the impact of pre-treatment drug resistance (PDR) on viral suppression (VS) [viral load [VL] <400 copies/mL] in adults who initiated 1st-line ART within the cluster randomised TasP trial in rural KwaZulu-Natal

HIV-positive adults enrolled from March 2012–June 2016 and initiated ART with VL data available were eligible. HIV whole genome sequences (WGS) were generated on Illumina MiSeq in recently-infected (RIn) adults with available plasma samples and chronically-infected (CIn) ART-naïve adults. WGS were assembled using Geneious software; a 2% threshold was used to assess minority drug resistant variants defined as representing <20% of the viral population. TDR was assessed using the WHO 2009 list of mutations. Cox regression was used to estimate hazard ratios. Adherence was measured by visual analogue scale

921 (854/1064 CIn (81%); 67/81 (83%) RIn) of 1,145 adults with sequences initiated ART. 838 (783/854 CIn (92%); 55/67 RIn (82%)) had follow up VL and contributed to the analysis. Median age was 35 years (y) (IQR 28, 47) in CIn and 27 y (23, 38) in RIn; 71% and 84% were female, respectively; 97% were on fixed dose combination of tenofovir/emtricitabine/efavirenz. In RIn, the prevalence of any TDR was 14.6%(95%CI 8.3-24.2) in majority virus and 23.6%(95% CI 15.2-34.9) in minority virus. In CIn, PDR prevalence was 8.8%(7.2-10.7) and 18.7%(16.2-21.3) in majority and minority virus, respectively. The K103N mutation was the most common in majority and minority viruses. Cumulative suppression at 12 months (m) was 97%. Median time to VS was 2.96m (IQR 2.76-3.94). After adjusting for sex, age, baseline VL and adherence, there was no evidence that PDR was associated with VL suppression (adjusted (a)HR 0.96, 95%CI 0.75-1.23 and aHR=1.12, 95%CI 0.89-1.42, for majority virus and minority virus, respectively, vs no mutations). High baseline VL (>100,000 vs <10,000) was associated with a decreased rate of VS (aHR 0.75; 0.62-0.91) and good adherence (≥95% vs <95%) was associated with an increased rate of VS (aHR 1.36; 1.11-1.66)

The prevalence of TDR is above the WHO threshold of 5% in this rural South African setting. With local guidelines recommending test and treat, strengthening early warning TDR indicators is required. However, our data suggest the clinical impact of this may be limited, if adherence to current 1st-line ART is good