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Abstract
Effects of highly active antiretroviral therapy (HAART) regimens containing the protease inhibitor (PI) nelfinavir on apoptosis of peripheral blood mononuclear cells.
Míró Ò.1, Villarroya J.2, López S.1, Garrabou G.1, Rodríguez de la Concepción M.2, Martínez E.1, Pedrol E.3, Escayola R.4, Giralt M.2, Cardellach F.1, Gatell J.M.1, Casademont J.1, Villarroya F.2
Introduction: Negative mitochondrial effects of nucleoside analogues have been firmly established. However, controversies regarding the effects of PI on mitochondria remain: while some authors have claimed that PIs have beneficial effects through inhibition of mitochondrially-driven apoptosis, other have reported an increase of apoptotic events. We evaluated the effects of HAART regimens containing the PI nelfinavir on peripheral blood mononuclear cells (PBMCs) expression of Bcl-2 (antiapoptotic protein) and cleaved, active caspase-9 (pro-apoptotic protein).
Methods: Present cross sectional study included 16 HIV negative patients (HIV-), 20 HIV positive patients naïve for antiretrovirals (HIV+) and 19 HIV positive patient receiving nelfinavir plus AZT+3TC or ddI+d4T (HIV+PI) as first line antiretroviral treatment at least during the previous 12 months. PBMCs were isolated and Bcl-2 and caspase-9 analyzed by Western blot. Bcl-2 expression was normalized by mitochondrial content using VDAC quantification, while caspase-9 expression was normalized by beta-actin. A pro-apoptotic index calculating the ratio caspase-9/Bcl-2 was also estimated.
Results: Bcl-2 expression was lower in HIV+ individuals than in HIV- (0.99±0.57 vs 1.60±0.92 respectively, p=0.08), while caspase-9 expression was higher (0.49±0.40 vs 0.14±0.08, p<0.01). Apoptotic index was very significantly increased in HIV+ respect to HIV- individuals (0.50±0.33 vs 0.06±0.04, p<0.001). HIV+PI patients exhibited a trend to normalization for Bcl-2 expression (1.25±0.88, p=0.34 respect to HIV+) as well as for caspase-9 expression (0.45±0.58; p=0.27 respect to HIV+), while apoptotic index significantly improved (decreased) (0.31±0.25, p<0.05 respect to HIV+). No differences were found between the subgroup of HIV+PI according to concomitant PI drugs either AZT+3TC or ddI+d4T.
Conclusions: HAART regimens containing the PI nelfinavir seems to have some beneficial effects to counteract the increased apoptosis present in HIV positive untreated people (Grant: Marató TV3•020210).
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
TuPe2.2B22
Suggested Citation
"MíróÒ., et al.
Effects of highly active antiretroviral therapy (HAART) regimens containing the protease inhibitor (PI) nelfinavir on apoptosis of peripheral blood mononuclear cells..
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
TuPe2.2B22"
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