HIV is associated with higher biological age compared to chronological age

Simon Collins, HIV i-Base

A new prospective cross-sectional cohort study reports that people older than 45 commonly have a higher biological age compared to their chronological age, and that the difference is higher for HIV positive people compared to a matched HIV negative control group.

The study was reported by Davide De Francesco and colleagues from the COBRA collaboration and published in the journal AIDS.

The analysis included 134 HIV positive participants on suppressive ART, 79 lifestyle-comparable HIV-negative participants >45 years old, and a further control group of 35 age-matched blood donors (who are screened for other infections and social and lifestyle behaviour­, including sexual risk and travel).

Biological age was calculated using 10 age-related biomarkers that have been previously shown to be best predictors of chronological age in a large European study. Results were adjusted for HIV history (CD4, CD8, viral load, ARVs) and other health-related social demographics including age, sex, sexuality, education, smoking, alcohol and recreational drugs, CMV, HBV and HCV.

All HIV positive participants were on effective ART with undetectable viral load (<50 copies/mL), with median CD4 count of 618 (IQR: 472 to 806) cells/mm3. Approximately one third had a history of previous AIDS.

The HIV positive participants had an average biological age that was 13.2 years older than their chronological age (95%CI: 11.6 to 14.9) compared to a biological age in the HIV negative control group that was 5.5 years older (95%CI: 3.8 to 7.2), both p<0.001. Biological age was also significantly higher for both groups compared to the blood donor controls whose biological age was –7.0 years younger than their chronological age (95%CI: −4.1 to −9.9) (both p < 0.001).

Higher biological age was significantly associated with chronic HBV (p=0.008), higher anti-CMV IgG titer (p=0.002) and higher CD8 T cells (p=0.02), independently of HIV status.

Among HIV positive participants, multivariate analysis showed CD4 nadir <200 cells/mm3was associated with biological age increase of 3.5 years (95%CI: 0.1 to 6.8).

The only HIV drug that was significantly associated with higher biological age (by 0.1 (95%CI: 0.06–0.2) years for each additional month of exposure) was the protease inhibitor saquinavir. There was a lack of association with mitochondrial toxic ARVs (d4T, ddI and ddC). However, the discussion in the paper notes this might be a limitation of the biomarkers (as there was also no association with current or past cigarette smoking).

The paper concludes that the results show HIV is more associated with accentuated rather than accelerated ageing, but that longitudinal follow-up is required to really answer this question.

The paper defined accentuated ageing as an increased burden of ageing-related damage while the year-on-year damage remains static over time. Accelerated ageing is defined as occurring when age-related complications occur earlier than expected with a progressive increase in the rate of decline.

De Francesco D et al on behalf of the Co-morbidity in Relation to AIDS (COBRA) Collaboration. Do people living with HIV experience greater age advancement than their HIV-negative counterparts? AIDS 33(2); 259–268. doi: 10.1097/QAD.0000000000002063. (01 February 2019). Full open access.

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