title: Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Building 10, Room 11C103, National Institutes of Health (NIH), Bethesda, MD 20892, USA. mpolis@nih.gov
authors.forename: M A
authors.initials: MA
authors.lastname: Polis
authors.forename: I A
authors.initials: IA
authors.lastname: Sidorov
authors.forename: C
authors.initials: C
authors.lastname: Yoder
authors.forename: S
authors.initials: S
authors.lastname: Jankelevich
authors.forename: J
authors.initials: J
authors.lastname: Metcalf
authors.forename: B U
authors.initials: BU
authors.lastname: Mueller
authors.forename: M A
authors.initials: MA
authors.lastname: Dimitrov
authors.forename: P
authors.initials: P
authors.lastname: Pizzo
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
authors.forename: D S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D015658:HIV Infections / Q000097:blood*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D016015:Logistic Models; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood* / Q000187:drug effects; D019438:Ritonavir / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D019438:Ritonavir