Determinants of virological failure after successful viral load suppression in first-line highly active antiretroviral therapy

Antivir Ther. 2008;13(7):927-36.

Abstract

Background: We aimed to investigate the long-term virological outcomes of a cohort initially showing good responses to first-line highly active antiretroviral therapy (HAART) with no evidence ofvirological failure during the first year after achieving viral load (VL) undetectability (<50 copies/ml).

Methods: Virological failure was defined as a confirmed VL >400 copies/ml or a single VL >400 copies/ml followed by a treatment change or end of follow-up. Risk factors for low-level VL rebound (50-400 copies/ml) in the first year after achieving undetectability and for virological failure during subsequent follow-up were investigated by logistic and Poisson regression.

Results: In the first year after achieving VL undetectability, 354/1386 (25.5%) patients experienced low-level VL rebound, the remaining patients maintained consistent undetectability. Low-level rebound occurred less commonly with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART than with other regimens (P = 0.01). Over median 2.2 (range 0.0-7.4) years of subsequent follow-up, 86 (6.2%) patients experienced virological failure, corresponding to 2.30 failures per 100 person-years (95% confidence interval [CI] 1.82-2.79). Independent predictors of virological failure included low-level rebound during the first year after achieving undetectability relative to consistent undetectability (rate ratio [RR] 2.18, 95%0 CI 1.15-4.10), female gender (RR 1.79, 95% CI 1.12-2.85) and receiving a ritonavir-boosted protease inhibitor (Pl/r) relative to NNRTI-based HAART (RR 1.88, 95% CI 1.02-3.46).

Conclusions: Patients on first-line HAART who maintain consistent VL undetectability for 1 year have a low risk of subsequent virological failure. A subset might benefit from targeted interventions, including women and patients on Pl/r-based HAART.

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4 Lymphocyte Count
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • HIV-1 / physiology*
  • Humans
  • Male
  • Predictive Value of Tests
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Factors
  • Sex Factors
  • Treatment Failure
  • Viral Load

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors