Is there anything left to learn? A report on the Fifth International Workshop on HIV Drug Resistance

Although insight into the viral dynamics of human immunodeficiency virus (HIV) infection has increased dramatically over the past year, there remains much to learn in the field of antiretroviral drug resistance. Transmission of isolates with primary drug resistance is increasingly recognized. With respect to reverse transcriptase inhibitors, it appears that the use of drugs in combination may forestall the development of resistance once therapy has been initiated. Further, certain findings, particularly with respect to zidovudine and lamivudine, suggest that emergence of resistance to one agent may lead to increased susceptibility to another. These data may allow evaluation of innovative treatment strategies to avoid the development of multidrug resistance, which has now been reported in a number of settings. Protease inhibitors (PIs) are, on an individual basis, the most potent antiretroviral compounds available today. A number of studies have shown that resistance to these agents develops after the accumulation of several mutations in the protease gene of HIV. As with reverse transcriptase inhibitors, the use of PIs in the context of regimens designed to suppress viral replication as much as possible appears to forestall, perhaps indefinitely, the development of drug resistance. Although different patterns of resistance mutations have been described for the different PIs available, the issue of cross-resistance remains unresolved. For the time being, it may be best to consider all PIs as a single agent that must always be used in a regimen designed to maximally suppress viral load. In conclusion, research in the field of antiretroviral drug resistance has never been more active and productive. It is hoped that such research will lead to the development of an integrated model of the clinical and laboratory management of HIV-infected individuals.