- Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature or accentuated ageing.
- Ageing can result from a mix of HIV infection, antiretroviral treatment, chronic viral co-infections and lifestyle or behavioural factors.
- In this study, age advancement appears to be related to viral co-infections such as CMV and chronic HBV, but also to historic severe immunosuppression and exposure to saquinavir.
People living with HIV (PLWH) with undetectable plasma HIV RNA may experience accentuated ageing compared with HIV-negative individuals with similar lifestyles, as estimated using a set of validated biomarkers of ageing.
A previous project (MARK-AGE) has proposed to combine biomarkers of human ageing (including immunological and neurological ones) to predict biological age of individuals. This study aimed to compare the MARK-AGE panel of biomarkers in order to evaluate the biological age of PLWH, demographically and lifestyle matched HIV-negative individuals, and blood donors with similar chronological age.
Associations were considered between age advancement and factors such as sociodemographics; smoking, alcohol consumption and drug use; CMV, chronic HBV and HCV infection; HIV disease parameters such as CD4+ and CD8+ T-cell counts, years since HIV diagnosis and exposure to antiretroviral drugs.
The study involved 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older and 35 age-matched blood donors. The 79 HIV-negative participants were comparable with the 134 HIV-positive participants in terms of age, sex, years of education, smoking and recreational drug use.
CMV, chronic HBV and HCV co-infections were all more frequent in HIV-positive participants compared with both the HIV-negative participants and blood donors. CMV was also more frequent in HIV-negative participants than in blood donors (due to the very strict requirements for blood donation in the Netherlands where the study was conducted).
All HIV-positive participants had plasma HIV RNA less than 50 copies/ml and were on antiretroviral therapy at study visit. They had a median (IQR) CD4+ T-cell count of 618 (472–806) cells/μl, and 31% had a prior clinical AIDS diagnosis.
Biological age was significantly greater than chronological age by a mean of 13.2 (95% CI 11.6–14.9) years in HIV-positive participants and by 5.5 (3.8–7.2) years in HIV-negative participants (P
Viral coinfections such as CMV and chronic HBV, as well as CD4+ and CD8+ T-cell counts and their ratio, appeared to be associated with increased age advancement.
Among the HIV-positive participants, positive correlations were found between age advancement and time since HIV diagnosis, duration of antiretroviral therapy and nadir CD4+ T-cell count
Cumulative exposure to saquinavir was also associated with an increased age advancement, which was independent of concomitant exposure to other drugs considered to have the greatest mitochondrial toxicities, and potential effects on ageing such as didanosine, stavudine, zalcitabine and zidovudine.