Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression

Long-term survivors (LTS) of human immunodeficiency virus type 1 (HIV-1) in fection provide an opportunity to investigate both viral and host factors t hat influence the rate of disease progression. We have identified three HIV -l infected individuals in Australia who have been infected for over 11 yea rs with viruses that contain deletions in the nef and nef-long terminal rep eat (nef/LTR) overlap regions. These viruses differ from each other and fro m other nef-defective strains of HIV-1 previously identified in Australia. One individual, LTS 3, is infected with a virus containing a nef gene with a deletion of 29 bp from the nef/LTR overlap region, resulting in a truncat ed Nef open reading frame. In addition to the Nef defect, only viruses cont aining truncated Vif open reading frames of 37 or 69 amino acids could be d etected in peripheral blood mononuclear cells isolated from this patient. L TS 3 had a viral load of less than 20 copies of RNA/ml of plasma. The other two long-term survivors, LTS 9 and LTS Il, had loads of less than 200 copi es of RNA/ml of plasma and are infected with viruses with larger deletions in both the nef alone and nef/LTR overlap regions. These viruses contain wi ld-type vif, vpu, and vpr accessory genes. All three strains of virus had e nvelope sequences characteristic of macrophagetropic viruses. These finding s further indicate the reduced pathogenic potential of nef-defective viruse s.