HIV-1 Fitness and Antiretroviral Drug Resistance

During the last few years, considerable new information has been obtained regarding HIV-1 replication capacity, often referred as viral fitness, and the potential effects on population size (viral load), drug resistance, and disease progression. Although viral fitness data originating from in vitro studies may not directly resemble in vivo clinical results, it offers a model to study and compare HIV-1 replication capacity and its relationship with drug resistance mutations. Treatment of HIV-1-infected individuals with antiretroviral drugs often results in selection of inhibitor-resistant variants with reduced replicative capacity. However, because of the remarkable plasticity of the HIV-1 genome, secondary/compensatory mutations are selected, which leads to the improving of viral fitness. Nevertheless, drug-resistant viruses with impaired fitness may pose a clinical benefit to the patient, by decreasing the levels of virus production and thereby delaying the emergence of highly resistant viruses. Characterization of the relative viral fitness of drug-resistant mutants under different selective pressures could lead to a better understanding of how specific drug resistance mutations emerge during therapy, and whether or not less fit viruses are beneficial for HIV-infected individuals.