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

Elsevier

Journal of Clinical Virology

Abstract

Background: The Sydney Blood Bank Cohort (SBBC) was infected between 1981 and 1984 with a nef/LTR defective strain of HIV-1. Different responses to HIV-1 infection have emerged between cohort members in the last 5 years. Three recipients (C135, C64 and C49) remain asymptomatic, have normal CD4 T cell counts, below detection (BD) viral loads (VL), remain therapy naive and are termed long-term non-progressors (LTNP). The donor (D36) and the two recipients (C98 and C54) have significantly declining CD4 T cell counts, detectable VL and are now long-term survivors (LTS). In contrast, in the SA cohort, comparison study group for the SBBC, five of 24 remain therapy naı̈ve after 15 years infection with HIV-1 and all have detectable VL. Objectives: This paper examines different outcomes to long-term infection with HIV-1 in the SBBC and provides a brief overview of the therapy naı̈ve in a comparison study group, the SA cohort. Study design: Retrospective epidemiological follow-up of the SBBC and the SA cohort has been conducted for >15 years. Analysis of CD4 T cell counts, VL and intermittent monitoring of HIV-specific proliferative responses are reviewed. Viral sequence changes in the SBBC will be considered. Results: Prior to therapy D36 had a CD4 T cell count of 160/mm3 and plasma VL of 9900 copies/ml while C98 had a CD4 T cell count of 387/mm3 and plasma VL of 11 491 copies/ml. After 1 month of therapy, plasma 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 strains, the most recently evolved quasispecies have larger deletions in the nef/LTR region. Conclusions: Infection with nef/LTR deleted HIV-1 has resulted in slower disease progression for the SBBC. The three LTNP have maintained normal low levels of activated CD8 T cells and strong HIV-specific proliferative responses to HIV-1 p24, which are associated with control of viral replication.

Section snippets

Background

The Sydney Blood Bank Cohort (SBBC) comprises one male donor and eight recipients who acquired HIV-1 from blood and blood product transfusions in Sydney between 1981 and 1984. Three of the eight recipients are deceased; two of the three deceased recipients died from causes unrelated to HIV-1 infection and a consensus has not been reached as to the cause of death of the third deceased recipient (Learmont et al., 1999).

The five remaining transfusion recipients have been infected with HIV-1 for

Methods

Informed consent was obtained from all participants. Plasma HIV-1 RNA was measured using COBAS Amplicor HIV-1 Monitor Version 1.0 (Roche, Branchburg, NJ) prior to July 1999 and COBAS Amplicor HIV-1 Monitor Version 1.5 after July 1999 using standard and ultrasensitive methods according to the manufacturers directions. The level of viral RNA detection is 400–50,000 copies/ml for Version 1.0 and 50–100,000 copies/ml for the ultrasensitive (Version 1.5). CD4 T cell counts by flow cytometry were

Results

Five of the SA cohort remain therapy naı̈ve after >15 years infection with HIV-1 (S6, S12, S17, S20 and S24). Unlike the SBBC, all the SA cohort have detectable VL. However, like C135 in the SBBC, several of the therapy naı̈ve possess viral and host factors associated with delayed progression – heterozygosity for the Δ32 deletion in CCR5 (S12 and S17) and preservation of CD4 T cell counts >550/mm3 over time (S6, S12, S17 and S20). Two of the five therapy naı̈ve have amino acid substitutions in

Conclusion

All the members of the SBBC have been infected with similar strains of nef/LTR defective HIV-1 (Deacon et al., 1996). After 16–19 years of HIV-1 infection, the SBBC can be divided into two distinct groups, LTNP and LTS.

The LTS have detectable low VL and significantly declining CD4 T cell counts over a long period of time (>15 years). The donor (D36) and one recipient (C98) commenced antiretroviral therapy in 1999 and the evolution of fitter viral strains has been demonstrated in both (Deacon et

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