Plasma Human Immunodeficiency Virus 1 RNA and CD4+ T-Cell Counts are Determinants of Virological Nonsuppression Outcomes With Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study

High baseline human immunodeficiency virus RNA levelsand low baseline CD4 T-cell counts are associated with higher rates of viral blips, low-level viremia, and residual viremia in people treated with integrase inhibitors or specifically with dolutegravir-based regimens, suggesting an independent impact of these characteristics. Background There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. Methods We included treatment-naive 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 Of 4310 eligible participants, 72% started 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 were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4(+) T-cell counts <= 200/mu L were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39-.68] and .40 [.27-.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4(+) T-cell counts <= 200/mu L were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02-4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Conclusions Initial high HIV-1 RNA and low CD4(+) T-cell 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(+) T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.

Automated summary

High baseline HIV RNA levels and low baseline CD4 T-cell counts are associated with higher rates of viral blips, low-level viremia, and residual viremia in individuals treated with integrase inhibitors or specifically with dolutegravir-based regimens, suggesting an independent impact of these characteristics.