Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
Predictors of Virological Failure and Time to Viral Suppression of First-Line Integrase Inhibitor-Based Antiretroviral Treatment.
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Pyngottu Ashima, Scherrer Alexandra U, Kouyos Roger, Huber Michael, Hirsch Hans, Perreau Matthieu, Yerly Sabine, Calmy Alexandra, Cavassini Matthias, Stöckle Marcel, Furrer Hansjakob, Vernazza Pietro, Bernasconi Enos, Günthard Huldrych F, Swiss HIV Cohort Study
Аннотация
BACKGROUND: Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.
METHODS: We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.
RESULTS: We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3-3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1-3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3-.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2-.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6-.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0-1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
CONCLUSIONS: Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
METHODS: We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.
RESULTS: We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio [mHR], 2.2; 95% confidence interval [CI], 1.3-3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1-3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3-.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2-.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6-.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0-1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
CONCLUSIONS: Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.