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Clinical management of virological failure remains an important and difficult issue for HIV physicians
One of the major barriers to successful treatment of HIV-1 infection is the emergence of drug resistant virus.1 The greatest impact of resistance is that it limits the effectiveness of subsequent antiretroviral combinations following initial drug failure. At a population level, more than 50% of patients who fail therapy do so with viruses resistant to drugs within at least one class of drug, with 15–20% with resistance to drugs within all three currently available classes (Health Protection Agency, unpublished data). Therefore, there is an urgent requirement for new drugs with activity against such resistant species. Over the past year or so, there has been a welcome upsurge in data presented on new drugs, both within existing classes and new classes, with the promise of more effective therapies for HIV resistant viruses (see table 1).
Nucleoside analogue drugs have been the mainstay of HIV therapy since zidovudine was first licensed in 1988,2 and it is not surprising that resistance to this class of drugs is most common at a population level (Health Protection Agency, unpublished data). Despite some specific signature mutations for individual nucleoside analogues, there is increasing evidence for cross resistance between certain drugs, such as ZDV and d4T, as well as the emergence of mutations conferring broad cross resistance, such as the 69 insertions, and the Q151M constellation of mutations within reverse transcriptase. Interesting data have been presented for alovudine, a thymidine analogue previously shown to have considerable toxicity in the clinic. Now reassessed at lower doses, activity is observed in patients with ZDV/d4T resistance (up to …