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T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective
J J Goedert1, T R O'Brien, A Hatzakis
1Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Objective:
To determine whether improved prediction of AIDS-free survival following HIV-1 seroconversion is achieved by measuring HIV-1 2-LTR episomal DNA (2-LTR) circles and T cell receptor rearrangement excision circles (TREC), reflecting HIV replication and lymphocyte emigration from the thymus, respectively.
Design:
Subanalysis of a cohort of 154 patients with hemophilia who became HIV positive between 1978 and 1985 and were followed prospectively.
Methods:
Relative hazards (RH) of AIDS, in the absence of highly effective anti-HIV therapy, were estimated for age, HIV-1 viral load, CD4 lymphocyte count and levels of HIV-1 2-LTR circles and TREC [per 106 peripheral blood mononuclear cells (PBMC)].
Results:
TREC correlated significantly with CD4 cell counts (r = 0.30) and age (r = -0.60). 2-LTR circles correlated significantly with HIV-1 viral load (r = 0.35). If viral load, CD4 lymphocytes and age were included in a proportional hazards model, the risk of AIDS during a median of 11.6 years of follow-up was increased significantly with fewer TREC (adjusted RH, 2.0 per log10 copies/106 PBMC) and more 2-LTR circles (RH, 1.7 per log10 copies/106 PBMC). AIDS prediction with TREC and 2-LTR circles held for most subgroups defined by median viral load, CD4 lymphocytes and age.
Conclusions:
PBMC that have high levels of HIV-1 replication and low levels of recent thymic emigrants are associated with a substantially increased risk of AIDS. It is not known if measurement of either TREC or 2-LTR circles will complement HIV-1 viral load as an estimation of the risk of AIDS for patients who are receiving highly effective anti-HIV therapy.