Telomere loss in peripheral blood mononuclear cells may be moderately accelerated during highly active antiretroviral therapy (HAART)

It has been speculated that infection with HIV-1 may lead to a significant increase in turnover, and subsequent exhaustion, of immune repopulation. Gi ven that telomeric DNA is lost on mitotic replication, telomere lengths can be used as an indirect gauge of this rate. We have analyzed the mean telom ere restriction fragment lengths in peripheral blood mononuclear cells (PBM C) from 31 patients with established, though mainly untreated, HIV infectio n and found them to be no different than those among healthy controls. Our results are in line with several findings in CD4(+) cell fractions but cont radict a previous report suggesting that telomere shortening contributes to immune failure, Interestingly, after approximately 2 years of subsequent a ggressive antiretroviral treatment we found a telomere reduction correspond ing to a loss of about 250 base pairs per year; this is roughly tenfold abo ve that predicted from healthy individuals. This could partly result from n ucleoside analogue inhibition of the natural telomere replacement enzyme, t elomerase-a reverse transcriptase inducible in certain hematopoietic cells. However, this may also indicate accelerated cell replacement on initiation of optimal therapeutic regimes or result from changes in the composition o f the PBMC pool. These results suggest careful monitoring of telomere lengt hs during long-term HAART.