Is ageing in people living with HIV accelerated or accentuated? - aidsmap

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No association was found between age advancement and ethnicity, sexual orientation or lifestyle factors. Associations were observed between an increased age advancement and CMV, chronic HBV, CD4 cell count, CD8 cell count and the CD4/CD8 ratio.

Among the HIV-positive participants, the parameters found to be positively correlated to biological age advancement were the time since HIV diagnosis, the duration of anti-HIV treatment and a nadir CD4 cell count below 200/mm3. There were correlations between age advancement and exposure to antiretrovirals, saquinavir in particular, for which each additional year of exposure represented a 1.39 years increase in age advancement.

A multivariable analysis (which controls for other factors that could influence the results) was conducted of all HIV-parameters, antiretroviral exposures, chronic HBV, total CMV IgG antibodies and CD8 T-cell count. It confirmed the significance of associations between age advancement and only:

  • Cumulative exposure to saquinavir (+ 1.2 years biological age per each year of exposure)
  • Nadir CD4 cell count below 200/mm3 (+ 3 years)
  • Chronic HBV (+ 7.4 years)
  • Total anti-CMV IgG antibodies (+ 1.9 years per each log IgG level increase).

Interestingly, current or past smoking did not appear to influence age advancement, but the study authors do not exclude the possibility that their markers may not have been specific enough to capture this factor, especially in a cohort where smoking frequency was low (12 cigarettes smoked per day in the COBRA groups).

The authors also highlight that the reasons why they found a significant association between duration of past exposure to saquinavir and advanced ageing are unclear to them. They were surprised to not obtain comparable results with other protease inhibitors, all known to promote vascular ageing through complex phenomena, and even other drugs such as D4T that induce the greatest mitochondrial toxicities. Therefore, these results should be interpreted with caution.

The finding on the role of CMV and HBV co-infections in advanced ageing, even among people on effective antiretroviral therapy, is easier to interpret. The two viruses may be responsible for premature ageing due to their chronic antigenic stimulation, which induces a systemic immune activation. In particular, CMV reactivation and concurrent immune responses to control infection have been known to be associated with ageing and increased morbidity and mortality in both the general population and people living with HIV.



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