Accumulated Mutations Cause Significant Fitness Losses and are Associated with Decreased Viral Loads During Early HIV-1 Infection

Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early and chronic infection affect viral fitness has not been well studied. We generated infectious molecular clones (IMCs) for the transmitted/founder (T/F), 6-month (6-mo) and 2-year (2-yr) viruses from the same infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo or 2-yr viruses to their cognate T/F viruses. We found that all ten 6-mo viruses were less fit than their cognate T/F viruses. Interestingly, 2-yr viruses that represented the clonally expanded viruses were more fit than the T/F viruses in two individuals. The fitness losses of the 6-mo viruses correlated with the decrease in viral loads from peak viremia. These results show that the mutations at month 6 of infection significantly reduce viral fitness and thereby contribute to lowering viral loads.