Incomplete HIV Type 1 Antibody Evolution and Seroreversion in Acutely Infected Individuals Treated with Early Antiretroviral Therapy

Abstract

The diagnosis of human immunodeficiency virus type 1 (HIV-1) infection by standard tests relies on the formation of HIV-1-specific antibodies. Early treatment of acute HIV-1 infection may have unique immunologic effects on host cellular and humoral responses. Rare cases of HIV-1 seroreversion have been reported for patients with advanced or rapidly progressive disease. Here, we report seroreversion that occurred in subjects with acute HIV-1 infection who initiated early antiretroviral therapy. A total of 150 patients with symptomatic acute or early onset HIV-1 infection that was treated with antiretroviral therapy were observed prospectively by means of monthly clinical and laboratory evaluation, which included serial HIV enzyme-linked immunosorbent assay and Western blots, until a fully evolved HIV-1 antibody response was documented. Three patients who initiated antiretroviral therapy a mean interval of 8 days (range, 1-16 days) after presentation and were observed for a mean duration of 50.2 months (range, 40.2-55.7 months) did not develop a fully evolved HIV-1 antibody response or demonstrated complete or partial HIV-1 seroreversion, despite maintenance of cytomegalovirus-specific humoral responses. Virologic suppression and seroreversion (complete or partial) occurred a mean duration of 4.1 months (range, 2.3-5.7 months) and 15.5 months (range, 6.7-26.3 months), respectively, after the initiation of therapy. All patients maintained complete virologic suppression while receiving therapy and had an undetectable HIV-1 RNA load at the time of seroreversion. Early antiretroviral therapy associated with durable virologic suppression in acute HIV-1 infection may abrogate the formation or detection of HIV-1-specific antibodies. Ongoing antigenic stimulation may be required to maintain HIV-1-specific humoral responses. Incomplete evolution of the HIV-1 antibody response and/or presence of seroreversion (although infrequently observed) underscore the potential unique immunologic effect of early antiretroviral therapy in patients with primary HIV-1 infection.