Background:  Remarkable progress has been made to prevent HIV-1 mother-to-child transmission (PMTCT) in resource-limited settings. However, viral resistance to Nevirapine^Ò, the first-line drug used in most national PMTCT programs, remains a critical issue. New ART and regimens must be identified and validated for PMTCT. To anticipate the future, we evaluate the efficacy of HIV-1 entry and fusion inhibitors to block cell-to-cell infection and the passage of the virus at the maternal-fetal interface.

Methods:  We used an in vitro double-chamber system consisting of a tightly polarized monolayer of BeWo cells (expressing CD4 or not), mimicking the placental trophoblast barrier in contact with infected maternal peripheral blood mononuclear cells (PBMC). Using this model, previously validated, we evaluate the capacity of entry (TAK779, AMD3100) and fusion (T20) inhibitors, to block the passage of R5, X4, and dual tropic HIV-1 across the BeWo barrier in vitro.

Results:  the CCR5 antagonist TAK779 and the CXCR4 inhibitor AMD3100, as summarized in the table, efficiently block the passage of virus resulting from cell-to-cell contact between BeWo cells (CD4⁺ or CD4^­) and PBMC infected with R5 and X4 viruses, respectively. An efficient inhibition of both R5 and R5X4 HIV-1 infection is also observed with the fusion inhibitor T20. However T20 does not block cell-to-cell infection by X4 HIV-1, but rather increases the passage of the virus.

Conclusions:  Our data show that CCR5 and CXCR4 antagonists are preventing HIV-1 infection resulting from a placenta-derived cell line in contact with infected PBMC. Our data also suggest that T20 might not be the best anti-HIV-1 agent to target cell-to-cell infection by X4 viruses. Further investigations on T20 as well as on other inhibitors of HIV-1 entry by cell-to-cell contacts are ongoing using our model to provide information about this new class of ART for future PMTCT trials.