An examination of signs of disease progression in survivors of the Sydney Blood Bank Cohort (SBBC)

Background: The Sydney Blood Bank Cohort (SBBC) was infected between 1981 a nd 1984 with a nef/LTR defective strain of HIV-1. Different responses to HI V-1 infection have emerged between cohort members in the last 5 years. Thre e recipients (C135, C64 and C49) remain asymptomatic, have normal CD4 T cel l counts, below detection (BD) viral loads (VL), remain therapy naive and a re termed long-term non-progressors (LTNP). The donor (D36) and the two rec ipients (C98 and C54) have significantly declining CD4 T cell counts, detec table VL and are now long-term survivors (LTS). In contrast, in the SA coho rt, comparison study group for the SBBC, five of 24 remain therapy naive af ter 15 years infection with HIV-1 and all have detectable VL. Objectives: T his paper examines different outcomes to long-term infection with HIV-1 in the SBBC and provides a brief overview of the therapy naive in a comparison study group, the SA cohort. Study design: Retrospective epidemiological fo llow-up of the SBBC and the SA cohort has been conducted for > 15 years. An alysis of CD4 T cell counts, VL and intermittent monitoring of HIV-specific proliferative responses are reviewed. Viral sequence changes in the SBBC w ill be considered. Results: Prior to therapy D36 had a CD4 T cell count of 160/mm(3) and plasma VL of 9900 copies/ml while C98 had a CD4 T cell count of 387/mm(3) and plasma VL of 11 491 copies/ml. After 1 month of therapy, p lasma VL was BD ( < 400 copies/ml) and both showed significant increase in CD4 T cell counts. Molecular changes have occurred in D36 and C98 viral str ains, the most recently evolved quasispecies have larger deletions in the n ef/LTR region. Conclusions: Infection with nef/LTR deleted HIV-1 has result ed in slower disease progression for the SBBC. The three LTNP have maintain ed normal low levels of activated CD8 T cells and strong HIV-specific proli ferative responses to HIV-1 p24, which are associated with control of viral replication. (C) 2001 Elsevier Science BN. All rights reserved.