Clinical trials of HIV drug resistance testing
- Paul E Sax, MD
Paul E Sax, MD
- Clinical Director, Division of Infectious Diseases
- Brigham and Women's Hospital
- Professor of Medicine
- Harvard Medical School
When successful, antiretroviral therapy durably controls viral replication. However, virologic suppression is not achieved in all patients and leads to virologic failure . Drug resistance is a major cause and a consequence of treatment failure. Clinicians can use genotypic and phenotypic assays to assess the susceptibility of a patient's virus to many available antiretroviral agents.
The major clinical trials that assessed the relative roles of these resistance assays will be discussed here. The performance of these tests, their relative advantages and disadvantages, and recommendations regarding the use of these assays in various patient groups are discussed elsewhere. (See "Overview of HIV drug resistance testing assays" and "Drug resistance testing in the clinical management of HIV infection".)
Several retrospective studies have demonstrated a correlation between baseline HIV-1 drug resistance and subsequent virologic outcome in patients with prior treatment experience [2-13]. A subsequent analysis of 12 different studies used consistent definitions of resistance and virologic outcome in order to combine clinical trial data . The primary end point for virologic failure in this analysis was plasma HIV-1 RNA concentration >400 copies/mL, 24 weeks after initiation of a salvage regimen. The analysis was significant for the following results:
●Both genotypic and phenotypic testing results were important predictors of virologic failure.
●The risk of virologic failure was reduced by twofold for each additional drug in the regimen, which was sensitive by genotypic testing and by two- to threefold for each additional drug identified by phenotypic testing.
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