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Significant Delay in Plasma vRNA Rebound during a Scheduled Treatment Interruption in HIV-1 Chronically Infected Patients Previously on Effective Therapy J. M. KILBY*, M. S. SAAG, P. A. GOEPFERT, R. D. HOCKETT, B. K. SAHA, and R. P. BUCY. Univ. of Alabama at Birmingham Five chronically HIV-1 infected male subjects on effective potent antiretroviral therapy with plasma vRNA < 200 copies for the previous 6 months stopped all antiretroviral medication for eight days and then restarted the same drug regimen. Only 2 of the 5 subjects experienced a significant rebound in plasma viral load during the scheduled treatment interruption (STI). Although 4 of 5 had undetectable plasma vRNA, each of the five subjects had detectable vRNA in PBMC before STI. The quantitative amount of vRNA or vDNA did not correlate with the time to viral rebound, however. The one subject who had a detectable viral load (100 copies/ml) prior to STI did not have significant rebound viremia after 8 full days completely off therapy. Both subjects who demonstrated viral load rebound off therapy had re-suppression of viral load to undetectable levels on the same combination regimen, indicating the lack of drug resistance development during this short drug holiday. Three of these subjects underwent lymph node biopsy at day 8 of therapy. In the tissue available, no increase in frequency of vRNA+ cells by in situ hybridization was detected above the low level previously found in effectively treated subjects. Analysis of PBMC by flow cytometry showed a slight, but statistically significant, decrease in CD4 count after the STI, with a return to baseline by 30 days after STI. Furthermore, there was an increase in the frequency of activated CD4 and CD8 T cells in the blood post STI, even in those subjects who did not demonstrate increased plasma vRNA off all antiretroviral therapy. The delay in detectable viral load rebound after discontinuation of all therapy suggests that the occasional "blips" of vRNA detected in subjects on continuous potent antiretroviral therapy may not be simply due to poor drug adherence. Key Words: HIV latent infection, immune activation, scheduled treatment interruption |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |