Am Fam Physician. 2001;64(8):1443-1444
Highly active antiretroviral therapy for human immunodeficiency virus (HIV) infection has led to marked decreases in the morbidity and mortality of infected persons. It also has greatly increased the expense and complexity of providing optimal antiretroviral therapy. HIV, like many viruses, can rapidly develop resistance to antiviral agents. Individual resistance patterns influence the success of initial anti-retroviral therapy and the selection of salvage therapy options for use in patients whose viral load does not suppress or later rebounds after a regimen is begun. Hanna and D' Aquila review the commonly available methods of detecting HIV drug resistance and make recommendations for their selected use.
The two categories of drug resistance testing are phenotypic assays and genotypic assays. In phenotypic assays, the ability of various antiretroviral drugs to inhibit HIV replication is quantified. Genotypic assays screen for genetic mutations in HIV that are known to confer drug resistance.
Phenotypic testing was initially a laborious process involving multiple cultures of HIV in the presence of varying concentrations of anti-retroviral drugs. Highly automated versions of phenotypic testing are now commercially available and have cut test-result time from more than six weeks to about two weeks. The phenotypic assay reports the concentration of a given antiretroviral medication that will inhibit HIV replication. Unfortunately, there is no general consensus as to what degree of increase in inhibitory drug concentration predicts clinical failure of that medication.
Genotypic assays are technically easier to perform because they involve the use of routine genetic probes and no laboratory cultivation of HIV. Various commercial methods are available. Not surprisingly, the most rapid methods (hybridization models) are somewhat less accurate than standard genetic sequencing, with error rates in the 4 to 8 percent range. One of the limitations of genotypic testing is the lack of a precise correlation between specific genetic mutations and in vivo HIV drug resistance, especially when multiple resistance mutations are present.
The authors included 12 clinical studies of drug resistance testing patients taking anti-retroviral therapy in their study. The odds of therapy failure were reduced about twofold to threefold for each antiretroviral drug that was verified effective by either phenotypic or genotypic assay. The authors note that the International AIDS Society–USA panel and the Department of Health and Human Services guidelines recommend the use of drug resistance testing in patients who are failing treatment. Testing should take place before the withdrawal of the failing medications to ensure that the mutated HIV strain is still present in sufficient numbers to be reliably detected.
The authors conclude with a suggestion for possible use of drug resistance testing at the beginning of antiretroviral therapy to determine if a resistant strain of HIV is already present.