A study in this week’s issue of THE LANCET highlights how very early (one week) assessment can reliably predict the long-term effectiveness of antiretroviral therapy for HIV-1.
Early assessment of antiretroviral drug efficacy is important for the prevention of the emergence of drug-resistant virus and unnecessary exposure to ineffective and toxic drugs. 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. Michael Polis, Dimiter Dimitrov, and colleagues from the US National Institute of Allergy and Infectious Diseases, and the National Cancer Institute, Bethesda, USA, investigated whether it was possible to assess drug efficacy from measurements of plasma HIV-1 concentrations made during the first week on therapy.
124 HIV-1-infected patients being treated for the first time with a protease inhibitor had their virus decay analysed for the first 12 weeks after the start of antiretroviral therapy. Patients with a continuous decline of HIV-1 concentrations and in whom HIV-1 was either undetectable or had declined substantially (by more than 1.5 log at 12 weeks) were defined as good responders; the rest were poor responders.
The virus decay rate at 6 days after the start of antiretroviral therapy was associated with changes in HIV-1 concentrations at 4, 8, and 12 weeks. 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.
Dimiter Dimitrov comments: “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.”
Contact: Dr Michael Polis, c/o Jeff Minerd, Office of Communications and Public Liaison, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 31, Room 7A-50, 31 Center Drive, MSC 2520, Bethesda, MD 20892, USA; T) +1 301 496 5719; F) +1 301 402 0120; E) jminerd@niaid.nih.gov
Professor Dimiter S Dimitrov, Laboratory of Experimental and Computational Biology, Center for Cancer Research, NCI-Frederick, NIH, Bldg 469, Rm 246, PO Box B, Miller Drive, Frederick, MD 21702-1201, USA; T) +1 301 846 1352; F) +1 301 846 6189; E) dimitrov@ncifcrf.gov
Journal
The Lancet