Viral resistance patterns selected by antiretroviral drugs and their potential to guide treatment choice

Abstract

Massive viral turnover and reverse transcriptase’s high error rate create the potential for drug-resistant viral variants to appear rapidly under the selective pressure of antiretroviral therapy. Loss of antiviral effect in treatment-adherent persons is most commonly coincident with the appearance of viral mutants with reduced drug sensitivity. Thus, detection of viral resistance may represent an early marker of therapy failure. Similarly, control of viral replication in the plasma compartment, as defined by plasma viral load below the levels of assay quantification, is associated with a sustained therapeutic response and delayed development of viral resistance. Information on patterns of resistance to and cross-resistance between antiretroviral agents is increasingly well characterised and represents an important consideration when deciding how to combine and/or sequence antiretrovirals to achieve optimal antiviral effects. Given the limited number of antiretrovirals presently available or in advanced development, it is important not to limit future therapeutic options by using therapies early in the treatment sequence which may select for cross-resistant viral variants and hence potentially reduce the magnitude of therapeutic response when treatment is changed to another member of that drug class. However, no studies using resistance to guide clinical decision making have been reported to date and available sequencing studies have focused largely on switching or adding therapies to patients experienced with zidovudine monotherapy. Thus, no resistance driven treatment algorithm is currently available.