Plasma viral load threshold for sustaining intrahost HIV type 1 evolution

The objective of the present study was to determine if natural suppression of plasma viremia below the detection limit of commercial assays (50-80 copies HIV-1 RNA/ml) can contain the HIV-1 evolution. HIV-1 quasispecies complexity in PBMC DNA was assessed in the env gene at two time points in 14 long-term nonprogressors (LTNPs). Sequence changes consistent with viral evolution was found in all patients with a median plasma RNA viral load >100 copies/ml. Evidence of low-level viral evolution was detected in two of four patients with intermittent viremia and a median plasma HIV-1 RNA load of >80 copies/ml. No significant evolution was observed in the three LTNPs with persistent viral suppression below the detection limit. Overall, a significant positive correlation (p < 0.001) was observed between viral evolution and plasma RNA viral load in the LTNPs analyzed. These results suggest that the detection limit of ultrasensitive viremia assays could represent an important threshold below which intrahost HIV-1 evolution does not occur.