Elevated hypermutation levels in HIV-1 natural viral suppressors

Abstract Mutations in the HIV-1 proviral genomes delay the progression of the disease. We compared the mutation status in full-length proviral genomes of 23 HIV-infected patients with undetectable viral loads in the absence of therapy named natural viral suppressors (NVS) or Elite Controllers with 23 HIV-infected controls (10 patients on HAART treatment and 13 untreated patients). Provirus DNA was extracted from PBMC for amplification and sequencing to determine the mutation status. Nine (39 %) of the 23 NVS patients had defective proviral genomes, compared to 4 of the treated controls (40%, p =0.96) and only one of the untreated controls (8%, p =0.059). Most of the defective genomes resulted from Gto-A hypermutation. Among patients with hypermutation, the rate ratio for mutation was significantly higher for the NVS compared to treated controls ( p =0.043). Our data suggests that inactivation of the virus through the APOBEC3G system may contribute to the NVS phenotype.