Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma

The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an i nfected individual; its measurement has become one of the most important pa rameters for monitoring clinical status'. Steady-state virus levels in plas ma reflect a balance between the rates of virions entering and leaving the peripheral blood(2). We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-fre e particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and v irus infectivity, that the clearance of physical and infectious particles f rom a primary, dual-tropic virus isolate, HIV-1(DH12), is very rapid in nai ve animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1(DH12)-specific neutralizing antibodies, the half-life o f virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles w ere eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding.