• Keynote: HIV drug resistance testing is worth the cost (MoOr31)
  Speaker: D. Mayers (United States)

• Keynote: The available evidence: where are we now? (MoOr32)
  Speaker: J. Mellors (United States)

• Keynote: What does it mean for the clinician? (MoOr33)
  Speaker: B. Clotet (Spain)

Keynote: HIV drug resistance testing is worth the cost (MoOr31)

On the whole the resistance symposium brought no news. Doug Mayers from Detroit gave a rapid review of the mechanisms of resistance. He stressed the importance of patients having an undetectable viral load to prevent failure. He explained the mechanisms of NRTI, NNRTI and protease inhibitor resistance, as well as the factors associated with failure. He then reviewed the technologies to detect both phenotypic and genotypic resistance. He commented on the results of both GART and VIRADAPT and summarized guidelines and indications for resistance testing.

Keynote: The available evidence: where are we now? (MoOr32)

John Mellors summarized our new understanding of the biochemistry of resistance and resistance reversal of NRTIs. Resistance to AZT is mediated by excision of AZT monophosphate from the terminated DNA chains by mutant RT. This excision reaction is catalyzed by PPi (pyrophosphate or NTPs). The presence of certain mutations (W88G) reverse AZT resistance (3TC, Foscarnet). The reversal is mediated by a reduced removal of AZTMP, which identifies a new potential target for drug discovery.

Mellors also demonstrated the consistency between baseline resistance and response to therapy by presenting a summary meta-analysis of 12 trials. He then went ahead to comment on VIRA 3001 and NARVAL, recently presented in the resistance conference in Barcelona (Spain). He said that we shouldn't expect too much from resistance testing. It will not provide all the answers. Other reasons will have to be considered for drug failure -- like adherence or low drug levels -- and we must work on developing tests to monitor these things.

Mellors concluded by talking about the need to redefine the interpretation of resistance test results. The current cut-off levels we use are inadequate: a 2.5-fold cut-off is too low for abacavir and four-fold is too low for ABT 378 or NNRTIs. Mellors thinks that we must work on developing better tests able to detect minor species (<20% of the sample) and to develop tests with improved sensitivities above the current 1,000 HIV RNA copes/ml limit.

Keynote: What does it mean for the clinician? (MoOr33)

Bonaventura Clotet provided a more clinical perspective and gave advice about the use of resistance tests. Clotet said that we need to focus on the specific clinical question we are asking when we use resistance testing. We need to ask what the test adds to our clinical judgment. And we need to do that before trying to interpret the results. We also need to consider the optimal timing of sampling: taking the test at first detectable viral load or wait until a specific viral load. When deciding what to use for rescue, Clotet stressed the importance of medication history and that every result has to be interpreted in the light of a patient's individual clinical situation.