Background: Patients initiating antiretroviral therapy (ART) with viral loads (VL) ≥100,000 copies/mL are less likely to achieve virologic success. We assessed the efficacy of dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL) and darunavir (DRV) on rates of virologic failure (VF).
Methods: ART-naïve patients with VLs ≥100,000 copies/mL initiating DTG, EVG, RAL, or DRV between 12Aug2013 and 31July2017 were identified. VF was defined as (i)2 consecutive VLs ≥200 copies/mL after 36 weeks of ART, or (ii)1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks, or (iii)2 consecutive VL ≥200 copies/mL after suppression (VL ≤50 copies/mL) before 36 weeks, or (iv)1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Analyses were conducted with Kaplan Meier methods and multivariate Cox modeling.
Results: There were 2,038 ART-naïve patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%) or RAL (2%). Median follow-up was 18.1 months (IQR: 12.4-28.9). EVG patients didn''t differ from DTG at baseline. RAL patients were older and more likely to be female with low CD4 counts. DRV patients differed notably, especially on baseline characteristics associated with risk for treatment failure. (Table 1) VF was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio for VF was 1.46 (95% CI: 1.05, 2.03) for EVG, 2.24 (1.50, 3.34) for DRV, and 4.13 (1.85, 9.24) for RAL. (Figure 1)
Conclusions: ART-naïve patients with high viral loads initiating on DTG were significantly less likely to experience VF compared to EVG, RAL and DRV initiators.

 DTG n=736EVG n=928DTG vs. EVG p-valueRAL n=48DTG vs. RAL p-valueDRV n=326DTG vs. DRV p-value
Median(IQR) Age(Yrs)32.8 (25.7-43.2)32.0 (25.9-43.7)0.809340.3 (28.7-47.8)0.020636.9 (28.7-45.4)0.0014
Female (n,%)90 (12.2%)99 (10.7%)0.603515 (31.3%)0.001546 (14.1%)0.6023
African American (n,%)311 (42.3%)418 (45.0%)0.255021 (43.8%)0.8391164 (50.3%)0.0149
Medicaid/Medicare/Ryan White (n,%)441 (59.9%)487 (52.5%)0.010529 (60.4%)0.4013206 (63.2%)0.2177
AIDS (n,%)196 (26.6%)239 (25.8%)0.686215 (31.3%)0.4844131 (40.2%)<.0001
VL≥500K copies/mL (n,%)147 (20.0%)208 (22.4%)0.227413 (27.1%)0.236396 (29.4%)0.0007
CD4 Count ≤200 (n,%)294 (39.9%)399 (43.0%)0.210030 (62.5%)0.0021205 (62.9%)<.0001
Median (IQR) VACS30 (20-53)30 (20-53)0.914346 (30-65)0.001849 (30-65)<.0001
Hx of Syphilis (n,%)208 (28.3%)267 (28.8%)0.818811 (22.9%)0.4240112 (34.4%)0.0459
[Table 1. Baseline Patient Characteristics by Core Agent]

Fig 1: VF Following Core Agent Initiation: Unadj. Cumulative Probability and Adjusted Hazard Ratio
[Fig 1: VF Following Core Agent Initiation: Unadj. Cumulative Probability and Adjusted Hazard Ratio]