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HAART Blocks the Accelerated Erosion of Telomeres Induced by HIV Infection
B Unryn, L Bestilny, K Riabowol, and M John Gill*
Univ of Calgary, Alberta, Canada
Background: HIV infection
induces rapid lymphocyte turnover and the accelerated loss of telomere sequence
that is believed to contribute to AIDS-associated immunosenescence. In this
study we asked if HAART, by reducing HIV viral load and restoring T-cell counts,
also arrested accelerated telomere erosion and if telomere length was restored
in T cells repopulating the circulation.
Methods: Blood samples from
16 HIV patients who had been characterized for telomere length in 1995 and
subsequently treated with HAART, were collected and telomere lengths of peripheral
blood mononuclear cells (PBMC) were determined and compared in parallel, pre-
and post-HAART. Archived DNA samples from our previous study and PBMC of the
same individuals 10 years after beginning HAART were purified, and telomere
length was measured in the same gels by terminal restriction fragment (TRF)
analysis.
Results: Treatment with
HAART blocked the accelerated telomere erosion normally seen in PBMC during HIV
infection (p <0.0001). Patients on
HAART showed an average loss of 65 bp/year compared with the ~52-bp/year loss
seen in age-matched populations and the >180 bp/year seen upon HIV infection
in the absence of HAART.
Conclusions: HAART blocks
the accelerated telomere erosion seen in the circulating component of the
immune system during HIV infection. However, it does not restore telomere sequences
previously lost, indicating that repopulation of PBMC from progenitor cells or
activation of telomerase does not restore replication potential. Preservation
of telomere length should be considered as a potential advantage favoring
earlier HAART use.
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