First demonstration of a lack of viral sequence evolution in a nonprogressor, defining replication-incompetent HIV-1 infection.

It is universally acknowledged that genetic diversity is a hallmark of HIV-1 infection, and it is one of the traits that has considerably hampered the development of an effective vaccine. In a study of full-length HIV-1 genomic sequences (>9 kb), we show unique evidence for complete absence of viral evolution in an individual with truly nonprogressive infection. Gross gene defects were not detected, but the state of replication incompetence was attributed to the presence of stop codons in the structural genes gag p17 and p24 and in pol RT, which emerged as a consequence of G-A hypermutation. These inactivating mutations may have occurred early, soon after infection, during the clonal stage of primary viral replication, since these are the sole archival strains present today. This genetic homogeneity, with <1% variation between strains over an 8-year period, suggests that only limited proviral integration events occurred in this patient. Further study on the antigenic properties of this strain may assist in the development of HIV vaccines and therapeutics.