IMMUNOLOGICAL AND VIROLOGICAL INTERACTIONS IN PATIENTS RECEIVING PASSIVE IMMUNOTHERAPY WITH HIV-1 NEUTRALIZING MONOCLONAL-ANTIBODIES

Mouse monoclonal antibodies with high human immunodeficiency virus typ e 1 (HIV-1) neutralizing titers were used for passive immunotherapy of eleven late-state HIV-infected patients. In five patients the serum l evel of the core protein p24 decreased, while in five cases it remaine d unchanged. The level of viral RNA in plasma as measured by quantitat ive polymerase chain reaction (PCR) decreased in four cases, was stabl e in another four, and increased in three cases. An anti-mouse (HAMA) response developed in eight patients and anti-idiotypic antibodies app eared in six. Immune complexes that formed in patient sera during the treatment were shown to contain mostly envelope glycoprotein gp120 whi ch decreased in nine of the eleven treated patients toward the end of treatment. Antibodies inhibiting gp120 binding to CD4 became detectabl e or increased in six patients during immunotherapy. Serology of the H IV-1 V3 region was studied for bath the HIV-1 IIIB and MN strains with no or very small changes in titer or avidity after treatment. No chan ge in neutralizing titers to strain HTLVIIIB was observed in serum sam ples collected before and after treatment was terminated. In nine of t he eleven patients stimulation of the T lymphocytes to proliferate in vitro when activated by phytohemagglutinin (PHA) was shown to be incre ased compared to before treatment. Increased T-cell proliferation was also noted with several antigens such as HIV-1 recombinant antigens, c ytomegalovirus (CMV), tetanus toroid (TT), and purified protein deriva te of mycobacterium tuberculosis (PPD). These findings indicate a decr eased total gp120 content in serum, permitting better T-cell activatio n.