Effectiveness of integrase strand transfer inhibitors among treatment-experienced patients in a clinical setting

Abstract

Objective: Characterize virologic and immunologic outcomes of INSTI-based antiretroviral therapy (ART) in experienced patients with and without virologic failure.

Design: Prospective clinical cohort.

Methods: ART-experienced, INSTI-naive participants in the University of North Carolina Center for AIDS Research HIV Clinical Cohort (UCHCC) initiating an INSTI-containing regimen 2007-2016 were followed from INSTI initiation (baseline) to the earliest of: outcome of interest, loss to follow-up (LTFU, 1 year without clinical visit), or death. Outcomes of interest were virologic failure (first of two consecutive viral loads at least 200 copies/ml more than 2 weeks apart, or one viral load ≥200 before LTFU) and immune recovery (first CD4 ≥500 cells/μl). Patients with baseline viral load at least 50 copies/ml were given 24 weeks before meeting virologic failure criteria. Kaplan-Meier curves and Cox proportional hazards models compared INSTI regimens and patient characteristics.

Results: Of 773 patients, 32% were women, 59% African-American, and 42% had a viral load at least 50 copies/ml at INSTI initiation. After 2 years, 5% of patients with baseline viral load less than 50 copies/ml experienced virologic failure, compared with 35% of patients with baseline viral load at least 50 copies/ml (P < 0.01). Among patients with baseline viral load less than 50 copies/ml, dolutegravir/NRTIs was associated with longer time to virologic failure [adjusted hazard ratio (aHR) 0.11, 95% confidence interval (CI) 0.01-0.80], whereas among patients with baseline viral load at least 50 copies/ml, raltegravir/NRTIs was associated with longer time to virologic failure (aHR 0.35, 95% CI 0.18-0.68), both compared with elvitegravir/NRTIs. After 5 years suppressed, irrespective of baseline viral load, 61% of patients experienced immune recovery.

Conclusion: In this cohort, INSTI-containing regimens led to low virologic failure rates in patients switching ART while suppressed. Viremic patients initiating INSTIs were at high risk of virologic failure during follow-up.

Figure 1.

Time from INSTI initiation to virologic failure stratified by INSTI regimen: (A) among patients with HIV viral load <50 copies/mL at INSTI initiation, (B) among patients with viral load ≥50 at INSTI initiation, (C) among patients with viral load ≥50 and aged <45 years at INSTI initiation, and (D) among patients with viral load ≥50 and aged ≥45 years at INSTI initiation.