Progressive human immunodeficiency virus-specific immune recovery with prolonged viral suppression

The degree of immune recovery achievable with anti-human immunodeficiency v irus (HIV) therapy remains to be established. The effects of potent antiret roviral therapy, including ritonavir and saquinavir, on immune function wer e studied for a prolonged period in 41 patients. After 96 weeks, 88% of pat ients had plasma HIV RNA levels below the limit of quantitation. There were continuous increases in CD4 lymphocyte counts and in CD4:CD8 ratios over t ime. About half the patients developed lymphoproliferative responses to HIV p24 antigen, and nearly all developed responses to phytohemagglutinin. Thi s occurred in parallel with increases in interleukin-12 production and expr ession of CD28 on CD8 lymphocytes, despite potential antiproliferative effe cts of protease inhibitors. Transient increases in virus load were temporal ly associated with loss of proliferative responses. The improved immune fun ction, including HIV-specific immunity in many subjects, demonstrates the p otential reversibility of HIV-induced immunodeficiency and does not identif y a limit to immune recovery.