Systemic immune activation in HIV-1-exposed uninfected Vietnamese intravascular drug users.

To assess immunological parameters, including markers of immune activation, in highly HIV-1-exposed uninfected (EU) Vietnamese intravascular drug users (IDUs) in comparison with HIV-1-infected IDUs and HIVunexposed controls, we determined peripheral lymphocyte phenotypes in fresh whole blood samples from 32 EU IDUs, 28 HIV+ IDUs, and 26 blood donors. We found higher levels of activation markers (CD38, HLADR) on CD4+ and CD8+ T cells, lower percentages of naive CD4+ and CD8+ T cells, higher percentages of CD8+ T cells and of CD8+ T cells expressing CD25, and lower levels of CXCR4+CD4+ T cells in EU IDUs than in unexposed controls. Despite several differences in CD4+ and CD8+ T cell subset phenotypes, both EU and HIV+ IDUs exhibited a pattern of peripheral immune activation. Lymphocyte activation in EU IDUs may reflect immune stimulation driven by viral infections other than HIV-1 and/or allogeneic stimulation associated with needle sharing. Our results suggest that immune activation does not necessarily favor HIV-1 transmission, but, on the contrary, may alter the susceptibility of EUs to HIV-1 infection and contribute to their resistance.

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.