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HAART Interruption Increases Immune Activation
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Lipopolysaccharide (LPS) changes in plasma of HIV-1-infected subjects during repeated treatment interruptions
IAS Capetown July 2009
Reported by Jules Levin
L. Palmisano, S. Baroncelli, C.M. Galluzzo, M.F. Pirillo, M.G. Mancini, L.E. Weimer, V. Fragola, M. Giuliano, S. Vella
Istituto Superiore di Sanità, Rome, Italy
Background: Increased levels of circulating lipopolysaccharide (LPS), a marker of immune activation, have been found in HIV+ subjects, and tend to decline with HAART. The purpose of this study was to verify the impact of repeated treatment interruptions (TI) on this marker.
Methods: Subjects were enrolled in the intermittent arm of a randomized clinical trial (ISS-PART), comparing intermittent and continuous HAART for 24 months.Plasma LPS was quantified at study entry (T0), 2 weeks after first TI (T0 +15) and 2 weeks after the 4th TI at month 13 (T13 + 15).
Results: We studied 48 subjects, on HAART for at least 2 years, with viral load < 400 copies/ml and 703 CD4/ml (median). Compared with 10 healthy donors, they had significantly higher LPS levels (median 7.71 and 5.97 EU/ml respectively, p = 0.026). Patients were retrospectively divided in two groups (Non Controllers, NC, or controllers, C) according to HIV-1 RNA levels > or ≤400 copies/ml during TIs. There were 11 C and 37 NC. At T0, groups were comparable for all parameters, including LPS. At T0+15, NC had higher values of HIV-1 RNA (p< 0.001) and CD8 (p = 0.045), but not of LPS. At T13+15 (4th TI), C and NC still differed for HIV-1 RNA and CD8; in addition LPS levels were higher in NC (median, 7.2 EU/ml) than in C (median 5.00 EU/ml) (p < 0.001). Plasma LPS and HIV-1 RNA values were strongly correlated (p < 0.002, R2=0.56).
Conclusions: Our results confirm a strong association between HIV-1 RNA and LPS levels. The increase in this marker after one year of intermittent HAART suggests that repeated episodes of uncontrolled viral replication, even if of limited duration, may partially reverse the favourable effects of HAART on immuneactivation.
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