Adherence, viral suppression, and resistance to antiretroviral therapy

Early views on the relationship between adherence and resistance postulated a bell-shaped relationship that required near perfect adherence to prevent the evolution of drug resistance. More recently, potent regimens have opened up the window of adherence such that moderate levels of adherence are capable of viral suppression. Recent data also suggest that each regimen class may have different adherence-resistance relationships. These regimen-specific relationships are a function of the capacities of resistant virus to replicate at different levels of drug exposure, which are influenced by the impact of mutations on susceptibility of the virus and ability of the virus to replicate. Specific patterns of adherence, such as treatment discontinuations, may influence the adherence-resistance relationship to combination regimens comprising medications with differing half-lives. Host genomics that alters antiretroviral drug distribution and metabolism may also affect adherence-resistance relationships. Matching antiretroviral patterns to individual adherence patterns, to extent possible, may improve viral suppression and limit emergence of resistance.