Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir

Several highly potent and broadly neutralizing monoclonal antibodies against HIV have recently been isolated from B cells of infected individuals. However, the effects of these antibodies on the persistent viral reservoirs in HIV-infected individuals receiving antiretroviral therapy (ART) are unknown. We show that several HIV-specific monoclonal antibodies—in particular, PGT121, VRC01, and VRC03—potently inhibited entry into CD4⁺ T cells of HIV isolated from the latent viral reservoir of infected individuals whose plasma viremia was well controlled by ART. In addition, we demonstrate that HIV replication in autologous CD4⁺ T cells derived from infected individuals receiving ART was profoundly suppressed by three aforementioned and other HIV-specific monoclonal antibodies. These findings have implications for passive immunotherapy as an approach toward controlling plasma viral rebound in patients whose ART is withdrawn.The sustained suppression of HIV replication by antiretroviral therapy (ART) has dramatically improved the clinical outcome of infected individuals (1). In addition, research directed at potential pathways toward the development of an effective preventive HIV vaccine has provided insights into the nature of the immune response to HIV infection (2, 3). In this regard, recent advances in antibody-cloning technologies have led to the discovery of several highly potent and broadly neutralizing monoclonal antibodies against HIV from B cells of HIV-infected individuals (4–7). Of interest, several studies have demonstrated that certain broadly neutralizing HIV-specific monoclonal antibodies can prevent acquisition of the virus, suppress viral replication, delay and/or prevent plasma viral rebound following treatment interruption in infected animals (8–14), and block cell-to-cell transmission of laboratory-adapted HIV in vitro (15). However, it is unclear what in vivo effects these antibodies might have on HIV in humans and, in particular, what effects they may have on the virus contained in the persistently infected CD4⁺ T cells of individuals whose plasma viremia is controlled by ART. These infected CD4⁺ T cells are considered to be the major obstacle to viral eradication (16–18) as well as a potential source of plasma viral rebound following discontinuation of ART in patients whose viremia had been well controlled in therapy (1). In this regard, considerable efforts in current HIV therapeutic research have been focused on developing strategies aimed at achieving sustained virologic remission in the absence of ART (1). This focus is especially important given that viral rebound and sustained HIV replication has been observed in almost all infected individuals whose plasma viremia had been well controlled while receiving ART and whose ART was subsequently withdrawn (19). Therefore, it is important to determine which, if any, of the many recently characterized HIV-specific monoclonal antibodies can inhibit viral entry into CD4⁺ T cells of HIV isolated from the latent viral reservoir as well as replication of reservoir virus in autologous CD4⁺ T cells derived from infected individuals whose plasma viremia was well-controlled on ART. Such knowledge is critical to establishing novel opportunities for passive immunotherapy to prevent plasma viral rebound following discontinuation of antiretroviral drugs. We conducted the present study to address this issue.