Scientific article
Open access

Predictors of virological failure and time to viral suppression of first-line integrase inhibitor-based antiretroviral treatment

CollaboratorsKaiser, Laurent
Published inClinical infectious diseases, vol. 73, no. 7, p. e2134-e2141
Publication date2021-10-05

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.

  • HIV
  • Drug resistance
  • Integrase strand transfer inhibitors
  • Minor drug resistance mutations
  • Treatment outcome
  • Anti-Retroviral Agents / therapeutic use
  • Cohort Studies
  • Drug Resistance, Viral / genetics
  • HIV Infections / drug therapy
  • HIV Integrase
  • HIV Integrase Inhibitors / pharmacology
  • HIV Integrase Inhibitors / therapeutic use
  • Humans
  • Treatment Failure
Citation (ISO format)
PYNGOTTU, Ashima et al. Predictors of virological failure and time to viral suppression of first-line integrase inhibitor-based antiretroviral treatment. In: Clinical infectious diseases, 2021, vol. 73, n° 7, p. e2134–e2141. doi: 10.1093/cid/ciaa1614
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ISSN of the journal1058-4838

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