[MoOrA1056] Reduced susceptibility to HIV-1 infection and high NK cell activity in Vietnamese exposed uninfected intravenous drug-users

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Reduced susceptibility to HIV-1 infection and high NK cell activity in Vietnamese exposed uninfected intravenous drug-users

[AUTHOR(S):] X.L. Truong, T.T. Luong, K.H. Tran, T.C. Cao¹, D. Scott-Algara, A. David, P. Versmisse, D. Perez-Bercoff, F. Barre Sinoussi, G. Pancino², V.N. Nguyen³, J.Y. Follézou⁴, I. Theodorou⁵

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1056

BACKGROUND: We have previously described a population of highly exposed seronegative individuals among intravascular drug users (IVDUs) in Ho Chi Minh City (Vietnam). The aim of this study was to identify immune factors of protection against HIV-1 in exposed uninfected (EU) IVDUs, focusing innate immunity, including NK cell responses.

METHODS: Forty-two EUs and 34 uninfected voluntary blood donors, as a control group, were included in our study. Peripheral blood lymphocyte subsets were analysed by flow cytometry. PBMC or CD4+ cell susceptibility to HIV infection was evaluated by infecting PHA-activated cells with primary and laboratory HIV-1 strains. NK cell lytic activity in PBMC was evaluated using K-562 and Daudi cell lines as target cells. Production of cytokines by NK cells was evaluated by intracellular staining and flow cytometry. Student t-test and Fisher exact test were used to compare the two groups.

RESULTS: T CD4+ cell number and TCD4/TCD8 ratio were lower in EUs than in control individuals. Reduced PBMC susceptibility to HIV-1 infection was observed for 18 out of the 42 EUs tested but only for 4 out of 34 controls. In most cases, HIV-1 infection of CD4+ cells was suppressed by CD8+ lymphocytes. In 3 EUs, the resistance to HIV-1 was due to a restriction of virus replication in CD4+ cells. NK cell lytic activity was significantly higher in EUs compared to controls (p<0.001). Accordingly, the proportions of NK cells producing IFN-γ, TNF-a, RANTES, MIP-1 a and b, were higher in EUs than in controls (p<0.01).

CONCLUSIONS: Our results indicate that resistance to HIV-1 infection in vietnamese EU IVDUs is associated with a reduced susceptibility of PBMC to HIV-1 infection and an increased NK cell activity. Multiple mechanisms may account for the natural protection against HIV-1 in these individuals, including a CD4+ cell refractory state to HIV-1 or anti-viral defences associated to the activation of immune system compartments such as CD8+ and NK cells.

Presenting author: Gianfranco Pancino

1Institut Pasteur, Unité de Biologie des Rétrovirus, Institut Pasteur, 75724 Paris, Vietnam.

2Institut Pasteur, Paris, France.

3Hôpital Binh-Trieu, Ho Chi Minh City, Vietnam.

4Hôpital Paul Brousse, Villejuif, France.

5Hôpital Pitié-Salpêtrière, Paris, France.

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