Efficient HIV-1 Trans Infection of CD4 T Cells Occurs in the Presence of Antiretroviral Therapy

Abstract

Antiretroviral therapy (ART) has dramatically improved the quality of life of people with HIV-1 infection (PWH). However, it is not curative, and interruption of ART results in rapid viral rebound. Cell-to-cell transfer of HIV-1, or trans infection, is a highly efficient mechanism of virus infection of CD4 T cells by professional antigen-presenting cells (APCs), that is, dendritic cells (DCs), macrophages, and B lymphocytes. Methods: APC from HIV seronegative donors treated with ART in vitro (CCR5 agonist, NRTI, PI and NNRTI, alone or in combination), were loaded with HIV R5-tropic HIVBal and mixed with autologous or heterologous CD4 T lymphocytes to assess trans infection. Ex vivo APC from chronic HIV-infected MACS participants before and after initiation of ART, were also loaded with HIV R5-tropic HIVBal and tested for trans infection against autologous or heterologous CD4 T lymphocytes. Virus replication was measured by p24 ELISA. Results: Here we show in vitro that antiretroviral drugs did not block the ability of DCs and B cells to trans-infect CD4 T cells, although they were effective in blocking direct cis infection of CD4 T cells. Moreover, ex vivo DCs and B cells from ART-suppressed PWH mediated efficient HIV-1 trans infection of CD4 T cells, which were resistant to direct cis infection. Conclusions: Our study supports a role for HIV-1 trans infection in maintenance of the HIV-1 reservoir during ART.