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Lack of correlation between plasma residual viraemia and total HIV-DNA in PBMCs of successfully treated patients

Abstract number: O327

Parisi S., Sarmati L., Dori L., Andreis S., Buonomini A., Montano M., Boldrin C., Nicastri E., Andreoni C., Scaggiante R., Vullo V., Palù G., Andreoni M.

Objectives: The origin of residual viremia (RV) in HAART-treated HIV-seropositive patients (pts) is unknown. Many investigators interpret RV as the result of ongoing cycles of replication, others as the reactivation of virus from latently infected cells. The aim of the study was to correlate the level of HIV-RNA in plasma and level of HIV-DNA in PBMCs in a cross-sectional analysis.

Methods: 195 HAART-treated pts who achieved virological suppression, as defined by two consecutive plasma HIV-RNA measurements <50 copies/ml, from at least 18 months were enrolled. On the basis of RV values, the pts were subdivided in 4 groups: pts with undetectable plasma RNA level (UL, <1 copy/ml), pts with low level (LL, >1–10 copies/ml), pts with high level (HL, >10–50 copies/ml) and pts with viral blip (VB, >50–400 copies/ml). RV was quantified by an ultra-ultrasensitive method based on a modified Amplicor HIV-1 Monitor 1.5 (Roche Molecular Systems, USA), with a detection limit of 1 copy/ml. To quantify the total proviral HIV-DNA copy number in PBMC, the Real Time TaqMan protocol published by J-P Viard was adapted, with a sensibility of 5 copies/106 PBMCs.

Results: 66 (33.8%) pts were UL, 63 (32.3%) were LL, 41 (21%) were HL and 25 (12.8%) were VB. UL pts had highest number of nadir CD4+cells compared to other groups (UL: 360 cells/ml, LL: 315 cells/ml, HL: 279 cells/ml and VB: 305 cells/ul; mean values). Not significant difference was detected in CD4 cell count in the four groups of pts (698, 764, 680 and 691 cell/ul, respectively; mean values). Twenty two patients had undetectable level of proviral DNA in PBMCs (10 UL, 2 LL, 9 HL and 1 VB). The 12 patients with undetectable proviral DNA but detectable residual viremia had a median of 22 copies of HIV-RNA copies/ml (range 12–81 copies/ml). Finally, 11 out of 31 (35.5%) pts with more than 1,000 copies of HIV-DNA/106 PBMCs had undetectable level of RV.

Conclusion: A lack of correlation between HIV proviral DNA and residual viremia levels in a cohort of virological long term suppressed pts was demonstrated. This study confirms the complex origin of RV and the need to evaluate the relevance of the impact of the new potent drugs, such as Integrase Inhibitors and CCR5 Inhibitors, on episomal viral DNA, on RV and on the long term treatment success.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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