T cell receptor excision circles and HIV-1 2-LTR episomal DNA to predict AIDS in patients not receiving effective therapy.
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.


METHODS
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.
Goedert
J J
JJ
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
O'Brien
T R
TR
Hatzakis
A
A
Kostrikis
L G
LG
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D000328:Adult; D000375:Aging / Q000276:immunology / Q000502:physiology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis; D005500:Follow-Up Studies; D016325:HIV Long Terminal Repeat; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012307:Risk Factors; D019562:Viral Load
D004279:DNA, Viral; D011948:Receptors, Antigen, T-Cell