Determinants of virological response to antiretroviral therapy: implications for long-term strategies

A variety of factors can contribute to the failure of combination antiretroviral therapy to durably suppress viral replication in patients infected with human immunodeficiency virus (HIV). Patients who have a low CD4(+) T cell count or high plasma viral load before therapy is initiated are at high risk for subsequent virological failure. Previous therapy is also a strong determinant of subsequent virological response, presumably because of pre-existing viral resistance. Drug exposure, as determined by adherence, drug absorption, and drug metabolism, has a significant impact on future long-term virological responses. Although definitive proof is lacking, some tissues may have limited drug penetration, thus allowing for ongoing viral replication. Understanding why combination therapy fails for HIV-infected patients may allow clinicians to individualize treatment strategies. Unfortunately, almost any factor (drug, host, or viral) that leads to virological failure of an initial combination regimen is likely to persist-and perhaps become more challenging-once a salvage regimen is initiated.