Selective increases in HIV-specific neutralizing antibody and partial reconstitution of cellular immune responses during prolonged, successful drug therapy of HIV infection

Because the immune response to HIV depends on viral gene expression, we exa mined the HIV-specific immune responses in persons whose viral load after h ighly active antiretroviral therapy (HAART) was <400 on at least 3 occasion s over a 12-month interval. Eleven patients were identified. While there wa s little change in mean HIV-binding antibody (Ab) titers in this group, two persons mounted increases in HIV envelope-specific binding antibody. Neutr alizing antibody (NAb) titers against a panel of HIV-1 primary isolates (BZ 167, US1, and CM237) increased post-HAART (80% neutralization titer against US1, p = 0.06; against CM237, p = 0.04). The two persons with large increa ses in binding antibody also had increases in primary isolate NAb. Roughly half of HAART recipients had significant increases in neutralizing antibody to the primary isolates US1 and CM237. Compared with CD4-matched, non-HAAR T controls, there were significant increases in NAb against the subtype B p rimary isolate US1 (p < 0.0009); no increases were seen against more easily neutralized primary isolate BZ167. There were no differences after HAART i n antibody-directed cellular cytotoxicity (ADCC). HAART resulted in a parti al restoration of lymphoproliferative responses to recall antigens (tetanus and diphtheria). New responses developed to HIV Gag p24. No patient respon ded to HIV Env gp160 or gp120 either before or after HAART. The data unders core the lack of functional reconstitution of HIV-specific, CD4-mediated re sponses despite durable suppression of viral replication. In the setting of stable anti-HIV Ab levels, the development of increased NAb in certain ind ividuals suggests that control of the virus by HAART may assist in immune c ontrol of HIV.