AIDS Treatment Update, Issue 54, June 1997
Keith Alcorn

Clinicians are wary about just 'tinkering' with a failing regimen because of the difficulty of knowing exactly which component(s) needs to be changed. They can sometimes make informed guesses; for instance, among people taking AZT/ddI or AZT/ddC in trials such as Delta, it was the emergence of resistance to the AZT component (rather than to ddI or ddC) which seemed to be associated with a decrease in antiviral efficacy. That might imply that people who fail on AZT/ddI or AZT/ddC could take d4T in place of the AZT, but continue on their current second drug, perhaps adding a further agent such as an NNRTI or a protease inhibitor as a added precaution.

Clinicians might feel more comfortable with this approach if they had access to a blood test that could reliably indicate to which drugs an individual's HIV remains susceptible, and to which it has become resistant. The first such test, known as the LiPA HIV-1 Reverse Transcriptase test, became commercially available this month; it can detect resistance mutations associated with AZT, ddI, ddC and 3TC. However, it will take longer for labs to gear up (and get funding) to use it, and for clinicians to assess its usefulness in guiding treatment decisions.

It is important to remember that the emergence of resistance may not be the only reason for a rising viral load during antiviral treatment. Treatment may also be failing because of problems absorbing or metabolising the drugs; or because of HIV-related damage to the immune system that is not necessarily restored by anti-HIV drugs. A resistance test will not address these factors. Some clinicians are concerned that the presence of specific resistance mutations in lab tests has not been clearly linked to treatment failure in real life, and over-reliance on such a test may encourage premature or inappropriate treatment changes.

A resistance test could also be useful for people who are about to start treatment for the first time. A small but growing proportion of newly infected people are contracting HIV strains that are resistant to AZT, and most authorities believe that it is only a matter of time before the transmission of a protease-resistant HIV strain is reported. A resistance assay could identify such people, helping them to choose an initial regimen of drugs to which their virus remains fully sensitive.

970601
ATU05402

Copyright © 1997 - AIDS Treatment Update. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. Subscription lists are kept confidential. NAM Publications 16a Clapham Common Southside, London, England SW4 7AB; TEL: 01-71-627-3200 (from outside the UK: +44-171-627-3200); FAX: 01-71-627-3101 (from outside the UK: +44=171-627-3101)  info@nam.org.uk  http://www.nam.org.uk