12th International AIDS Conference Geneva, Switzerland - June 28-July 3, 1998

Int Conf AIDS 1998 Jun 28-Jul 3; 12:10 (abstract no. 11140)

Rhodes D, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N;;; Macfalane Burnet Centre for Medical Research, Fairfield, Vic., Australia.

BACKGROUND: The lack of disease progression in a small number of people infected with HIV-1 has been attributed to defects in the nef/LTR region of several HIV strains. We assembled a group of 69 long-term nonprogressors (LTNPs) to ascertain the frequency at which nef/LTR deletions occur in LTNPs and to screen for the presence of attenuated strains previously identified in an Australian group of transfusion recipients and their common donor.

METHODS: DNA was isolated from uncultured PBMCs and the nef/LTR region of the provirus was amplified using triple nested PCR. The products were cloned and sequenced using a LiCor 4000 L automated sequencer.

RESULTS: In three of nine individuals with viral loads less than 200 RNA copies/ml, deleted nef/LTR regions only could be amplified. In the remaining 48 individuals with viral loads greater than 200, either mixed populations of wild type and deleted nef/LTR forms of wild type nef/LTR regions alone were detected. The three deleted viruses lacked different sequences but all maintained regions known to be essential to viral replication. The three patients have been infected for at least 10 years, have CD4 counts higher than 800/microliter and are culture negative.

CONCLUSIONS: The proportion of nef deleted viruses in LTNPs with viral loads < 200 copies/ml is high in our group of LTNPs. The three patients identified are most likely LTNPs due to the genomic defects detected in the nef/LTR region. The three nef deleted viruses do not possess deletions characteristic of the SBBC strains. These new vaccine candidate strains are important to the furthering of live attenuated HIV-1 vaccine research.

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