Telomerase Activity of Peripheral Blood Mononuclear Cells in HIV and HIV/HCV Coinfected Patients

REYNOSO R, LAUFER N, BOLCIC F, QUARLERI J.

Cape Town, South Africa

Conferencia; 5th. IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2009

International AIDS Society

Background: Replicative senescence of lymphocytes play an important role in the pathophysiology of chronic viral infections. Although there are controversial reports concerning telomerase activity in HIV monoinfected subjects, no data on HIV/HCV-coinfected individuals is available. Methods: PBMC were obtained from 31 subjects grouped in G1:9-HIV+/HCV-, G2:11-HIV+/HCV+, and G3:11 healthy blood donors as control. Only HIV-HCV coinfected patients were under ARV therapy. None was under pegylated-IFN based treatment. Telomerase activity (TA) was quantified in non-stimulated and PHA-stimulated PBMC lysates using Real Time PCR. Viral load (VL), HCV genotype, CD4+ T cell count, and liver histology parameters were measured. Statistical analyses were performed with t-test and significance threshold was set at p<0.05. Results: G1 was younger (35 ±8.8 yrs-old) than G2 (43.64 ± 6.6, p=0.01), and had a shorter time of known HIV infection (3.79 ± 2.11 yrs vs. 16.7 ± 4.7, p=0.000). In G1 median log HIV VL was 4.11UI, in G2 was undetectable, and median log HCV VL was 6.43UI. No significant differences were found regarding gender and CD4+ T cell count (G1: 213.9 ± 87.33 vs. G2: 455 ± 156.8, p =0.35). In G2 95% exhibited HCV genotype 1 (both in PBMC and serum) and liver biopsy was available in 6/11, 66.6% had METAVIR F3-F4. No significant differences were found in basal TA between the three groups, however the increase of enzymatic activity after mitogenic stimulus was only significant in G3; furthermore in activated PBMCs TA was significant higher in G3 than G2. Conclusions: In our population TA in PBMC of HIV monoinfected and HIV/HCV-coinfected patients couldn’t be up-regulated in the same range of healthy donors. Moreover, TA of activated PBMCs from health donors was significantly higher than coinfected ones. The lack of an appropriate induction of TA after stimulus could be partly responsible for immunosuppressive condition in such patients.