The Sydney Blood Bank Cohort comprised eight individuals who were infected with an attenuated, nef/LTR-deleted strain of HIV-1 from a single donor. All six recipients with sufficient follow-up, as well as the donor, were long-term nonprogressors. Only three recipients have maintained undetectable plasma viral loads, allowing investigation of factors that determined elite control of attenuated HIV-1 infection.
Follow-up of recipients showed that infection with this attenuated HIV-1 strain resulted in either low or absent viral replication in vivo for up to 29 years. The three patients without detectable viraemia have been studied for virological, genetic and immunological correlates of elite control. CD4 proliferation in vitro in response to p24 provided the clearest distinction of elite controllers from the slow progressors. Host factors are believed to differentiate the three elite controllers; only one, C135, has identifiable genetic polymorphisms that probably contributed to nonprogression: Δ32 CCR5 heterozygosity, HLA-B57 and HLA-DR13 alleles, in addition to infection with nef-defective HIV-1.
Even nef-defective HIV-1 can lead to sufficient replication in vivo to enable viral evolution and eventual progression to immunodeficiency. Host factors modified the outcome of infection with attenuated HIV-1, as exemplified by the unique patient C135.
aCentre for Applied Medical Research, St. Vincent's Hospital, University of New South Wales, Australia
bResearch and Business Development, Australian Red Cross Blood Service, Australia
cTransfusion Medicine and Immunogenetics Research Unit, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
dCentre for Virology, Macfarlane Burnet Institute for Medical Research and Public Health, Australia
eDepartment of Medicine, Monash University, Melbourne, Victoria, Australia
Correspondence to John Zaunders, Centre for Applied Medical Research, Level 9 Lowy Packer Building, St. Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010, Australia Tel: +61 2 8382 4945; fax: +61 2 8382 4967; e-mail: firstname.lastname@example.org