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Members of the Sydney Blood Bank Cohort (SBBC) have been infected with an attenuated strain of HIV-1 with a natural nef/LTR mutation and have maintained relatively stable CD4+ T lymphocyte counts for 14-18 years. Flow cytometric analysis was used to examine the phenotype of CD4+ and CD8+ T lymphocytes in these subjects, including the immunologically important naive (CD45RA+CD62L+), primed (CD45RO+), and activated (CD38+HLA-DR+ and CD28-) subsets. The median values were compared between the SBBC and control groups, comprising age-, sex-, and transfusion-matched HIV-1-uninfected subjects; transfusion-acquired HIV-1-positive LTNPs; and sexually acquired HIV-1-positive LTNPs. Members of the SBBC not only had normal levels of naive CD4+ and CD8+ T lymphocytes, but had primed CD45RO+ CD4+ T lymphocytes at or above normal levels. Furthermore, these primed cells expressed markers suggesting recent exposure to specific antigen. SBBC members exhibited variable activation of CD8+ T lymphocytes. In particular, SBBC members with undetectable plasma HIV-1 RNA had normal levels of activated CD8+ T lymphocytes. Therefore, the result of long-term infection with natural nef/LTR mutant HIV-1 in these subjects suggests a decreased cytopathic effect of attenuated HIV-1 on susceptible activated CD4+ T lymphocyte subsets in vivo, and minimal activation of CD8+ T lymphocytes.

We have reported previously a cohort of long-term survivors of HIV-1 infection, known as the Sydney Blood Bank Cohort, who received HIV-1-positive blood from a common infected donor. A new recipient, C135, has been identified. This recipient became infected after receiving blood donated during the presumed time of seroconversion of the donor in February 1981. C135 has been infected for more than 18 years without signs of disease progression. The virus load in this recipient has remained below the detectable level (<20 RNA copies/ml of plasma) and repeated Western blot analyses have given an indeterminate result. By booster PCR techniques we have demonstrated that this individual is infected with HIV-1 and have characterized the viral nef and nef/LTR region sequences present. The strain of HIV-1 identified contains deletions of 88 bp from the nef alone region and a total of 139 bp deleted from the nef/LTR overlap and LTR regions. The LTR contains three wild-type Sp1 transcription factor-binding sites, the 3' wildtype NF-kappaB site, and a duplicated Sp1 and NF-kappaB region. A truncated Nef protein of only 19 amino acids is encoded. The deletions and rearrangements in the nef gene and LTR sequences are characteristic of Sydney Blood Bank Cohort strains of virus. The identification of C135 increases the Sydney Blood Bank Cohort size to nine individuals and represents a rare example of a genuine, long-term HIV-1 infection accompanied by indeterminate anti-HIV-1 serology.

Our study not only confirmed cell surface antigens previously reported to be related to HIV disease stages, but also identified 5 novel ones. Of these five, three markers point to major changes in responsiveness to certain cytokines, which are involved in Th1 responses. For the first time our study shows how density of cell surface antigens could be efficiently exploited in an array manner in relation to HIV disease stages. This new platform of identifying disease markers can be further extended to study other diseases.

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