Normal CD95 (APO-1/Fas)-Induced T Cell Apoptosis Despite High Plasma Viral Load in HIV-1-Infected Children and Adolescents Receiving Highly Active Antiretroviral Therapy

Abstract

Based on previous studies on the influence of antiretroviral treatment on CD95-induced T cell apoptosis cross-sectional data on T cell apoptosis and T cell homeostasis were analysed from 29 pediatric patients treated for more than 6 months either with 2 nucleosidic inhibitors of HIV-1 reverse transcriptase (group A, 20 observations) or HAART containing at least 1 inhibitor of HIV-1 protease (group B, 16 observations). Seven patients were studied twice. The relationship between specific anti-CD95-induced apoptosis of freshly isolated peripheral blood CD4 + and CD8 + T cells with the percentage of circulating CD4 + T cells, HIV-1 RNA plasma viral load levels and the proportion of circulating resting/naive and primed/memory CD4 + T cells was assessed. Seven patients in each group had HIV-1 plasma viral load levels ≤ 3.0 log RNA-copies per ml. In group A, CD95-sensitivity of T cells increased significantly with low CD4 counts, and tended to rise with low proportions of resting/naive CD4 cells and high HIV-1 plasma viral load levels. In group B, the sensitivity of peripheral blood T cells towards CD95-induced apoptosis was not increased compared to controls and was not correlated with CD4 + T cell counts and CD4 + T cell subpopulations or HIV-1 plasma viral load levels. These data indicate that treatment with HAART including HIV-1 protease inhibitors has an inhibitory effect on CD95-sensitivity of circulating T cells. This effect, which is independent of the reduction of HIV-1 plasma viral load levels by HAART, may contribute to the amelioration of CD4 + T cell homeostasis frequently seen in HAART-treated patients despite virological treatment failure.