8th Annual Conference Of The British HIV Association [BHIVA] 19 – 21 April 2002, University of York, York

[AUTHOR(S):] J Morlese, I Teo, JW Choi, BG Gazzard, S Shaunak
Hammersmith Hospital and Chelsea & Westminster Hospital, London

BHIVA Conf 2002 Apr 19-21;8:O10

BACKGROUND: On-going viral replication in patients on antiretroviral therapy leads to treatment failure. We have shown that the 2-long terminal repeat (LTR) circle assay can be performed on peripheral blood mononuclear (PBMN) cells to monitor acute infection events throughout the body even when plasma HIV-1 RNA is <50 copies/mL. A new LightCycler (LC) based circle assay was used to prospectively monitor a cohort of HIV-1+ patients on antiretroviral therapy.

METHODS: The circles in PBMN cells, plasma HIV RNA and CD4 count were prospectively measured at regular intervals over a 2-year period in 60 patients on antiretroviral therapy. Their plasma HIV-1 RNA was <50 copies/mL at all times. 2-LTR circles were extracted from PBMN cells by plasmid extraction and then quantified using the LC.

RESULTS: All patients maintained a plasma HIV-1 RNA of <50 copies/mL for 31±2 months. The circles were monitored for 15±1 months of these months. The circle copy number ranged from <10 to 400 copies/10⁶ PBMN cells. 58% of the patients had no detectable circles (<10 copies/10⁶ PBMN cells). 42% had detectable circles (>10 copies/10⁶ PBMN cells). The two groups were mutually exclusive (P<0.001) and the circle copy number remained stable over the period of follow-up. A single circle-copy measurement was as reliable as multiple measurements to establish the presence of persistent viral replication. There was no correlation between circle-copy number and CD4⁺ or CD8⁺ T-cell count.

CONCLUSIONS: The circle assay is a simple method of identifying those patients with persistent viral replication despite an undetectable plasma HIV RNA. 42% of the patients with successful long-term suppression of plasma HIV RNA still had persistent viral replication. New drug combinations and therapeutic approaches are needed for these patients.

PRESENTING AUTHOR: J Morlese

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