<qa>  What is the main obstacle to the successful long-term suppression of HIV replication?Although, the use of protease inhibitors PI containing highly active antiretroviral therapy HAART has led to a remarkable improvement in the prognosis and outcome of HIV infection, only 45 to 70 of treatment-naïve patients who commence HAART achieve complete virological suppression. The emergence of HIV resistance to antiretroviral drugs is one of the main obstacles to the successful long-term suppression of HIV replication. Poor adherence and unfavorable pharmacokinetics PK caused by altered absorption, genetic variations in metabolism and drug-drug interactions frequently lead to antiretroviral drug concentrations below the inhibitory concentration for 50 of the viral quasispecies IC50 and loss of viral suppression. 