CD4 cell and CD8 cell-mediated resistance to HIV-1 infection in exposed uninfected intravascular drug users in Vietnam.

OBJECTIVE: To identify mechanisms of resistance to HIV-1 infection in exposed uninfected individuals. DESIGN: We examined in-vitro cell susceptibility to HIV-1 infection in highly exposed Vietnamese intravascular drug users (IDU) who, despite a history of more than 10 years of drug use and a high prevalence of other blood-borne viral infections, remain apparently HIV uninfected. METHODS: Forty-five exposed uninfected IDU and 50 blood donors were included in the study. Peripheral blood mononuclear cells (PBMC) or CD4 cell susceptibilities to HIV infection were evaluated using three HIV-1 isolates with different tropisms. Polymerase chain reaction analysis of HIV-1-DNA replication intermediates was used to characterize the restriction of HIV-1 replication in CD4 cells. Homologous CD8 cells were mixed with infected CD4 cells to evaluate their role in virus suppression. RESULTS: We observed a relative resistance to PBMC infection with HIV-1 in 21 out of 45 exposed uninfected IDU, but only in five out of 50 unexposed controls (P < 0.001). PBMC resistance was related either to an inhibition of HIV-1 replication in CD4 cells or to CD8 cell-mediated viral suppression. HIV-1 replication in CD4 cells was restricted at the early stages of the viral cycle. CONCLUSION: Reduced PBMC susceptibility to HIV-1 infection was associated with resistance to infection in exposed uninfected IDU. Distinct mechanisms are involved in in-vitro resistance and may contribute to the apparent protection from HIV-1 transmission in this systemically exposed population.

Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users.

We addressed the role of innate immunity in the protection against HIV-1 infection by studying NK cell function in 37 Vietnamese intravascular drug users (IDUs), who appeared to remain HIV-1 uninfected despite many years of high-risk exposure (exposed uninfected, EU), 10 IDUs who underwent seroconversion and 28 unexposed blood donors. Main results were: NK cell lytic activities against both the NK-susceptible K562 cell line and the NK-resistant Daudi cell line were significantly augmented in EU IDUs compared with either controls or seroconverters before or after seroconversion; NK cells producing the cytokines IFN-gamma and TNF-alpha and the beta chemokines CCL3, CCL4, and CCL5 were also increased in the EU IDUs, either after in vitro activation or without stimulation. The finding of an enhanced NK cell function in EU IDUs, especially compared with IDUs who became HIV-1 infected, supports the hypothesis that NK cells contribute to the protection against HIV-1 infection.