Plasma HIV-1 RNA and CD4+ T-cell counts are determinants of virological non-suppression outcomes with initial integrase inhibitor-based regimens: A prospective RESPOND cohort study

Background: There are conflicting data regarding baseline determinants of virological non-suppression outcomes in persons with HIV who initiate antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. Methods: We included treatment-naïve participants aged ≥18 who initiated 3-drug ART, in 2014-2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV) and virological failure (VF) rates were assessed using Cox regression. Results: Out of 4,310 eligible participants, 72% initiated integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91·0% and 93·3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates of viral blips were 9·6%, LLV 2·1%, RV 22·2% and VF 2·1%. Baseline HIV-1 RNA >100,000 copies/mL and CD4+ count ≤200 cells/µL were negatively associated with VS at weeks 48 (aOR 0·51; 95%CI:0·39-0·68 and 0·40; 95%CI:0·27-0·58, respectively) and 96, and with significantly higher rates of blips, LLV and RV. CD4+ counts ≤200 cells/µL were associated with higher risk of VF (aHR 3·12; 95%CI:2·02-4·83). Results were consistent in those starting INSTIs versus other regimens and those initiating dolutegravir versus other INSTIs. Conclusions: Initial high HIV-1 RNA and low CD4+ counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV and RV. Low baseline CD4+ counts are associated with higher VF rates.These associations remain with INSTI- and specifically dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.