Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs

Diane L. Bolton, Amarendra Pegu, Keyun Wang, Kathleen McGinnis, Martha Nason, Kathryn Foulds, Valerie Letukas, Stephen D. Schmidt, Xuejun Chen, John Paul Todd, Jeffrey D. Lifson, Srinivas Rao, Nelson L. Michael, Merlin L. Robb, John R. Mascola, Richard A. Koup

Combination antiretroviral therapy (cART) administered shortly after HIV-1 infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required in the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (mAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein specific broadly neutralizing mAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received i) the CD4-binding site mAb VRC01 or ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent mAb (PGT121) or iii) daily cART, all on day 10, just prior to expected peak plasma viremia, or iv) no treatment. Daily cART was initiated 11 days after mAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, mAb treatment significantly reduced peak viremia, accelerated the decay slope and reduced total viral replication as compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with dual mAb. These data demonstrate the virological effect of potent mAbs and support future clinical trials that investigate HIV-1 neutralizing mAbs as adjunctive therapy with cART during acute HIV-1 infection. Treatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 mAbs has been shown to significantly reduce plasma viremia. However, the anti-viral effect of mAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that mAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of mAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.