REDUCED CELL SUSCEPTIBILITY TO HIV-1 INFECTION IN VIETNAMESE EXPOSED UNINFECTED INTRAVENOUS DRUG-USERS

Truong Xuan Lien, Luong Thu Tram, Nguyen Van Ngai,
Cao Huu Nghia, Tran Kim Hung, Cao Thu Cuc, Tran Ton

Gianfranco Pancino, Annie David, Pierre Versmisse, Daniel Scott-Algara,
J-Y Follézou, Ioannis Theodorou, Françoise Barré-Sinoussi

ABSTRACT

Persons who remain uninfected despite a high degree of HIV exposure form a population enriched with individuals who are naturally protected against the virus. This study aims to identify immune factors associated to the protection against HIV-1 infection in exposed uninfected (EU) intravenous drug users (IVDUs) in Vietnam.

We have previously described a population of highly HIV-exposed seronegative IVDUs in Ho Chi Minh City (Vietnam). The CCR5D32 mutation, which was associated to HIV-1 resistance in caucasian individuals, was not found in this vietnamese population. In this study, 33 ENIs were collected from a cohort of IVDUs followed since December 1996 in the Rehabilitation Center of Binh Trieu in Ho Chi Minh City. All subjects were HIV-negative by serology and PCR for proviral DNA. Fifteen low risk uninfected voluntary blood donors were enrolled as a control group.

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 three HIV-1 isolates (the primary isolate HIV-1 132W, the R5 HIV-1 BaL and the X4 HIV-1 NL-4.3). Homologous CD8+ cells were added to infected CD4+ cells to evaluate their role in virus suppression. The production of ß-chemiokines in cell culture supernatants was quantified by ELISA. In some cases, PCR amplification of the different forms of HIV-1 genome was performed to characterize the restriction of viral replication in T CD4+ cells.

FACS analysis revealed significant differences in lymphocyte phenotypes between EU and control group by activation markers and lymphocyte subsets. Reduced susceptibility to at least one of the 3 HIV-1 isolates (mostly to the R5 isolate) was observed in the PBMC of 18 of 33 EU individuals but not in control PBMC. In some cases, the resistance to HIV-1 was associated with a restriction of virus replication in CD4+ cells. In other cases, HIV-1 infection of target cells was inhibited by CD8+ lymphocytes. Only in part of these last cases high levels of secreted b-chemokines were found and could account for HIV-1 inhibition.

In conclusion, our data indicated that low susceptibility of PBMC to HIV-1 infection correlates with protection against the virus in the EU IVDUs. Different factors appear involved in the reduction of cell susceptibility to HIV-1 infection and may contribute to in vivo resistance in this population: a refractory state of CD4+ cells to HIV-1, b-chemokine secretion or other undefined T CD8+ viral suppressor factors.