Dolutegravir (DTG)+lamivudine (3TC) was shown to be as effective as triple therapy in RCT on patients (pts) switching during virological suppression, but limited data are available about the use of this regimen in pts with previous virological failures (VF), since RCT excluded these pts.
The analysis included data of HIV+ pts with HIV-RNA<=50 c/ml enrolled in a retrospective multi-cohort study across Italian infectious disease clinics switching for the first time to DTG+3TC from any other regimen (baseline). Primary endpoint was viral rebound (VR, confirmed HIV-RNA >=50 c/mL). Kaplan-Meier curves were used to estimate probabilities of VR according to history of previous VF (single HIV-RNA >=1000 or confirmed HIV-RNA >=50 c/mL). Weighted Cox regression model was fitted to estimate causal HR of VR, after controlling for confounding variables (time of viral suppression and nadir CD4). A further analysis with a different definition [Def 2] of previous VF (only at NRTI or INSTI regimens) and of VR (that included also a single HIV-RNA>=50 c/ml followed by change of therapy) and a sensitivity analysis excluding pts with incomplete history of viral load data (>1 year gap in measurements) were performed.
966 pts included: 74% males, median age 51 (IQR 44-57), 15% CDC-C stage, nadir CD4 246 (99-372), years of viral suppression 7 (3-12), 80% without previous VF, 12% with one previous VF, 8% with >=2 previous VF. VR was detected in 11 pts over 1555 person-year-follow-up (PYFU): total incidence ratio (IR) was 0.7 x 100 PYFU (95% CI 0.4-1.3), 0.5 x 100 PYFU (0.2-1.1) in pts without previous failures and 1.4 x 100 PYFU (0.6-3.4) in pts with >=1 previous VF, with an estimated 1-year probability of 0.4% (0.1-1.4) and 1.3% (0.3-5.3) respectively (log-rank p=0.071). With Def 2, VR was detected in 18 pts, IR 1.2 x 100 PYFU (0.7-1.9), 1.9 x 100 PYFU (0.6-1.8) in pts without previous failures and 1.9 x 100 PYFU (0.8-4.2) in pts with >=1 previous VF. By multivariate analysis, pts with 1 previous VF had higher risk of VR but not statistically significant throughout all the analyses (table), while having >=1 previous VF resulted to be associated to VR in the two sensitivity analyses.
Despite the increased risk of VR in pts with previous VF, especially in those with >=1 VF, the 1-year VR was very low. Although longer follow-up is needed to confirm this observation, current data suggest that DTG+3TC should be cautiously used in pts with current viral suppression but a history of VF