258-T. Relative Resistance to HIV-1 Infection in Vietnamese Exposed Uninfected Intravenous Drug Users

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Session 45 Poster Session
Exposed Uninfected Individuals
Session Time: 4:30-6:30 pm
Room 4E-F

258-T.

Relative Resistance to HIV-1 Infection in Vietnamese Exposed Uninfected Intravenous Drug Users
T. X. Lien¹, L. T. Tram¹, D. Scott-Algara*¹, A. David¹, P. Versmisse¹, D. Perez-Bercoff¹, N. V. Ngai², J-Y. Follézou³, I. Theodorou⁴, F. Barré-Sinoussi¹, and G. Pancino¹
¹Inst. Pasteur, Paris, France; ²Hosp. Binh-Trieu, Ho Chi Minh City, Vietnam; ³Hosp. Paul Brousse, Villejuif, France; and ⁴Hosp. Pitié-Salpêtrière, Paris, France

Background: Most studies on HIV-1-exposed seronegative individuals are focusing on HIV-specific immune responses in sexually exposed populations. This study aimed to analyse immune factors of protection against HIV-1 in intravenous drug-users who are at high risk of infection by systemic route not only for HIV but also for other blood transmitted pathogens. These individuals, therefore, are susceptible to have a persistent activation of their immune system. We identified a population of HIV-exposed uninfected individuals (Eus) among intravascular drug users (IVDUs) in Ho Chi Minh City (Vietnam). A very high prevalence (near to 100%) of other viral infections, such as HBV, HCV, HTLV-1 was found in both uninfected or infected IVDUs. None of the IVDUs were presenting the DELTA32 mutation of the HIV co-receptor CCR5.
Methods: 40 Eus and 25 low-risk uninfected voluntary blood donors, as a control group, were included in our study. Peripheral blood lymphocyte subsets and activation markers were analyzed by flow cytometry on whole blood. Peripheral blood mononuclear cells (PBMC) or CD4+ cell susceptibility to HIV infection was evaluated by infecting PHA-activated cells with a Vietnamese IVDU primary HIV-1 isolate or with X4 or R5 HIV-1 strains. Homologous CD8+ cells were added to infected CD4+ cells to evaluate their role in virus suppression.
Results: The number and percentage of CD4+ cells were lower in Eus than in control individuals whereas the percentage of CD8+ cells was higher, and most of them were CD8+/CD62L-. Reduced susceptibility to at least one virus (mainly R5 tropic) was observed for the PBMC of 18 out of the 40 Eus tested but only for 2 out of 25 controls. In most cases, HIV-1 infection of CD4+ cells was suppressed by CD8+ lymphocytes. The CD8+ associated suppression was either restricted to R5 viruses with, in some cases, a relationship with the secretion of high levels of beta-chemokines, or it was independent of the viral tropism. In 3 individuals, the resistance to HIV-1 was due to a restriction of virus replication in CD4+ cells.
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. They also suggest that multiple mechanisms may account for the natural protection against HIV-1 in these individuals. These mechanisms include a CD4+ cell refractory state to HIV-1 or anti-viral defences associated to the activation of some compartments of the immune system as suggested by the increase of CD8+ memory cell population in EU compared to controls.