Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy

Lancet. 2001 Nov 24;358(9295):1760-5. doi: 10.1016/s0140-6736(01)06802-7.

Abstract

Background: Early assessment of antiretroviral drug efficacy is important for prevention of the emergence of drug-resistant virus and unnecessary exposure to ineffective drug regimens. Current US guidelines for changing therapy are based on measurements of plasma HIV-1 RNA concentrations 4 or 8 weeks after the start of treatment with cut-off points of 0.75 or 1.00 log, respectively. We investigated the possibility of assessing drug efficacy from measurements of plasma HIV-1 concentrations made during the first week on therapy.

Methods: The kinetics of virus decay in plasma during the first 12 weeks of treatment was analysed for 124 HIV-1-infected patients being treated for the first time with a protease inhibitor. Patients with a continuous decline of HIV-1 concentrations and in whom HIV-1 was either undetectable or declined by more than 1.5 log at 12 weeks were defined as good responders; the rest were poor responders.

Findings: The individual virus decay rate constants (k) at day 6 correlated significantly (r>0.66, p<0.0001) with changes in HIV-1 concentrations at 4, 8, and 12 weeks, and correctly predicted 84% of the responses with a cut-off value of k=0.21 per day (in log scale). Reduction in plasma HIV-1 of less than 0.72 log by day 6 after initiation of therapy predicted poor long-term responses in more than 99% of patients.

Interpretation: These results suggest that changes in HIV-1 concentration at day 6 after treatment initiation are major correlates of longer-term virological responses. They offer a very early measure of individual long-term responses, suggesting that treatment could be optimised after only a few days of therapy.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Child
  • Clinical Trials as Topic
  • Cohort Studies
  • HIV Infections / blood*
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1*
  • Humans
  • Indinavir / therapeutic use
  • Logistic Models
  • Predictive Value of Tests
  • RNA, Viral / blood*
  • RNA, Viral / drug effects
  • Ritonavir / therapeutic use

Substances

  • HIV Protease Inhibitors
  • RNA, Viral
  • Indinavir
  • Ritonavir