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.

Identification of a cluster of HIV-1 controllers infected with low replicating viruses.

Long term non-progressor patients (LTNPs) are characterized by the natural control of HIV-1 infection. This control is related to host genetic, immunological and virological factors. In this work, phylogenetic analysis of the proviral nucleotide sequences in env gene from a Spanish HIV-1 LTNPs cohort identified a cluster of 6 HIV-1 controllers infected with closely-related viruses. The patients of the cluster showed common clinical and epidemiological features: drug user practices, infection in the same city (Madrid, Spain) and at the same time (late 70's-early 80's). All cluster patients displayed distinct host alleles associated with HIV control. Analysis of the virus envelope nucleotide sequences showed ancestral characteristic, lack of evolution and presence of rare amino-acids. Biological characterization of recombinant viruses with the envelope proteins from the cluster viruses showed very low replicative capacity in TZMbl and U87-CD4/CCR5 cells. The lack of clinical progression in the viral cluster patients with distinct combinations of protective host genotypes, but infected by low replicating viruses, indicate the important role of the virus in the non-progressor phenotype in these patients.