11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:11 (abstract no. Mo.A.382)
Goudsmit J, De Wolf F, Lukashov VV, Van Oers RH, Bakker M, Boucher CA, Danner SA; Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Fax: 31-20-6916531.

OBJECTIVE: To assess the role of availability of HIV-1 susceptible cells and T cell immunity in the maintenance of HIV-1 steady-state levels during infection. Materials and

METHODS: Two late stage HIV-1 infected male homosexuals received two syngeneic bone marrow transplants (BMT) each, one with and one without prior hemato-ablation. One patient received antiretroviral monotherapy before his first BMT without sustained impact on the steady-state levels of CD4+ cell numbers, HIV-1 serum RNA copy numbers and p24 antigen load. HIV-1 RNA levels were measured in serum, collected before, at and after BMT by using the nucleic acid sequence based amplification (NASBA) assay. P24 antigen concentration and CD4+ cell numbers were determined at the same time points. Results of bone marrow evaluation of 36 healthy individuals showing 8.2% (SD 3.5%) of nucleated cells to be CD3+ (CD4/CD8) and results of CD4/CD8 ratio testing among 1200 healthy adults showing to be 1.01 to 3.99 (90% confidence interval) and 0.6 to 5.4 (95% confidence interval) were used to calculate the number of CD4+ cells infused. CD4+ cells were considered as HIV-1 susceptible cells.

RESULTS: Hemato-ablation resulted in a decrease of CD4+ cell numbers below detection level and a simultaneous reduction of HIV-1 RNA copy numbers of approximately 1 log. Assuming the added number of CD4+ cells following BMT as stable in order to establish an upper limit of HIV-1 production per CD4+ cell, HIV-1 production per exogenous CD4+ cell was estimated to be 200 viral copies in one patient and 700 viral copies in the other patient. Following BMT without hemato-ablation, in one patient still a large number of virions were produced, whereas in the other the addition of CD4+ cells without hemato-ablation did not result in an increase of HIV-1 production.

DISCUSSION: These data suggest that (I) drastic removal of activated short lived CD4+ target cells has a significant, but not complete reducing effect on HIV-1 RNA levels, (ii) presentation of finite numbers of CD4+ target cells to the virus results in the production of finite numbers of HIV-1 copies and (iii) in some patients T cell immunity might be effective in removing large numbers of newly infected cells.

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