The study of Quashie et al. showed that the presence of R263K mutation did confer a decreased integration in cell culture without altering reverse transcription step . Further in vitro experiments performed in this study, including biochemical cell-free assays performed with purified integrase enzyme containing R263K mutation, showed a slight decrease in 3′processing and strand transfer activities compared to the wild-type virus. Structural modeling suggested that the R263K mutation affects integrase-DNA interactions and in vitro integrase-DNA binding assays confirmed these data  (Figure 1). In the study of Mesplède et al., they performed prolonged infections by transferring culture fluids from infected cells to uninfected cells at weekly intervals and it resulted in a progressive decrease in integrated viral DNA between weeks 2 to 4 of infection. Thus, prolonged infections with R263K mutants led to a progressive decline in integrated HIV-1 DNA over time .