The effect of highly active antiretroviral therapy on binding and neutralizing antibody responses to human immunodeficiency virus type 1 infection

The effect on humoral immune responses of highly active antiretroviral ther apy (HAART) commenced during primary or chronic human immunodeficiency viru s type 1 (HIV-1) infection was investigated. HAART inhibited the developmen t of anti-gp120 antibodies when initiated during primary infection and coul d sometimes reduce antibody titers in patients treated within 2 years of HI V-1 infection. Conversely, antibody responses in patients infected for seve ral years were less sensitive to HAART. Administering HAART during primary infection usually did not substantially affect the development of weak neut ralizing antibody responses against autologous virus. However, 2 patients t reated very early after infection did not develop neutralizing responses. I n contrast, 3 of 4 patients intermittently adherent to therapy developed au tologous neutralizing antibodies of unusually high titer, largely coinciden t with brief viremic periods. The induction of strong neutralizing antibody responses during primary HIV-1 infection might require the suppression of virus replication by HAART, to allow for the recovery of immune competency, followed by exposure to native envelope glycoproteins.