Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384.

Author(s): Gandhi RT, Spritzler J, Chan E, Asmuth DM, Rodriguez B, Merigan TC, Hirsch MS, Shafer RW, Robbins GK, Pollard RB, ACTG 384 Team

Affiliation(s): Massachusetts General Hospital, Boston, MA, USA. rgandhi@partners.org

Publication date & source: 2006-08-01, J Acquir Immune Defic Syndr., 42(4):426-34.

Publication type: Randomized Controlled Trial

OBJECTIVE: To assess the effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy (ART). METHODS: Nine hundred eighty antiretroviral-naive HIV-1+ subjects were randomized to start stavudine/didanosine or zidovudine/lamivudine with nelfinavir, efavirenz, or both nelfinavir and efavirenz. RESULTS: Greater CD4 cell recovery was associated with age of 40 years or younger, female sex, higher baseline naive/memory CD4 cell ratio, higher baseline virus load (VL), and virologic suppression (VS). Most subjects who maintained an undetectable VL had a substantial increase in CD4 cell count, but 13% of the subjects did not, even after 3 years of VS. Persistent T-cell activation was associated with lower CD4 cell recovery, even in subjects who achieved VS. Initial treatment assignment did not affect total CD4 cell recovery, naive/memory CD4 cell reconstitution, or decline in T-cell activation. In addition to CD4 cell recovery, B-cell counts rose substantially after ART initiation. CONCLUSIONS: In this large randomized trial, younger age, female sex, higher naive/memory CD4 cell ratio, higher baseline VL, and VS were associated with greater CD4 cell increase, whereas persistent T-cell activation was associated with impaired CD4 cell recovery after ART initiation. Initial treatment assignment did not affect CD4 cell reconstitution.