Session 114Poster Presentations HIV Transmission Session Day and Time: Tuesday 1:30 - 3:30 pm Room: Hall B
903 First Evidence Showing Transmission of HIV-1 from a Non-progressor to Two Recipients M. Mikhail*1, B. Wang1, B. Beckthold2, J. M.Gill2, N. K.Saksena1 1Westmead Millennium Inst, Sydney, Australia and 2Alberta HIV Clin, Alberta, Canada
Background: Although several transmission cases of HIV have been described, viral transmission from an HIV-infected non-progressor (with below detection plasma viremia and high CD4 and CD8+ T-cell counts) to other recipients and their subsequent progression to AIDS has never been reported. The rarity of such HIV cohorts accents their existence as invaluable human models which may provide a clear understanding of molecular factors contributing to the rapid, slow, and non-progression of HIV disease. Irrespective of the immense literature available on HIV genetic variation, the actual relationship between viral variability and HIV disease progression and/or non-progression can only be extrapolated through epidemiologically-linked HIV-cohorts. Here we present a detailed analysis of full-length HIV-1 genomes, over time, from a transfusion acquired epidemiologically-linked cohort of 3 patients (donor A, a non-progressor, and 2 progressing recipients, B and C).
Methods: Fifteen (15) near full-length proviral HIV-1 genomes (8.7 kb) were derived longitudinally from peripheral blood cells using primer pairs in the LTR and the nef-LTR regions. The full-length genomes were amplified in a single round PCR and the subsequent PCR reactions were conducted using gene walking with gene-specific primer pairs. The fragments were cloned into PGEMT vector to verify significant molecular changes in HIV genomes. HLA typing of each patient (pt) was carried-out using PCR.
Results: Full-length HIV genomes from all 3 pts (A, B, and C) showed evidence for epidemiologic-linkage between them. In addition, significant contribution of CTL escape mutants, host-induced divergence and molecular changes viral genes such as nef, tat, and gp41 possibly led to disease progression in 2 recipients. Such changes were absent in the donor. A unique observation was the demonstration of transmission of a minor variant from a non-progressor to 2 progressing recipients who progressed to AIDS.
Conclusions: HIV-infected non-progressors with undetectable viremia, high CD4 and CD8+ T-cell counts and strong immune system harbor the potential to transmit HIV. They may carry minor HIV variants that may lead to HIV disease progression in other recipients. Molecular changes in the nef, env, gp41, and tat have considerable CTL escape potential and they may play a significant role in HIV disease progression.
