Aging in Patients With HIV

People living with HIV (PLWH) often show signs of premature or accentuated aging compared with their HIV-negative counterparts. However, a research team called the Co-morBidity in Relation to AIDS (COBRA) Collaboration has examined this further and has published data that may contradict previous findings.¹

Davide De Francesco, lead author of the study and research assistant in the Institute for Global Health at University College London, answered questions about this research.

Consultant360: Can you tell us more about your study and what you found?

Davide De Francesco: We evaluated a novel method to assess the ageing process in a group of treated PLWH with sustained viral suppression and compared with that of HIV-negative individuals with similar lifestyles and healthy blood donors.

The method used to assess what we call age advancement (ie, the extent of age-related changes in body function and composition in excess to those that would be expected in the average population at the same chronological age) was derived by an independent study that identified biomarkers of ageing across a range of physiological systems, among 3200 people from the general population across Europe.

According to this algorithm, on average, PLWH had an age advancement of 13.2 years, so appeared 13.2 years older than their chronological age. At the same time, HIV-negative individuals with a lifestyle similar to that of PLWH had an age advancement of 5.5 years, while blood donors appeared 7 years younger than their chronological age. 

C360: What factors were associated with increased age advancement in PLWH? Why were those important to study? 

Mr De Francesco: We used a rather explorative approach and studied a wide range of HIV-related and non-HIV-related factors. Among these, a nadir CD4 cell count below 200/mm3, cumulative exposure to saquinavir, chronic hepatitis B, and anti-cytomegalovirus (CMV) IgG antibodies were all independently associated with increased age advancement in PLWH. 

Low nadir CD4 cell count is a proxy of episodes of severe immunodeficiency due to untreated HIV infection. Its association with age advancement could reflect the longstanding impact of untreated HIV, even in patients who are now virally suppressed.

Saquinavir is a protease inhibitor, a class of antiretroviral drugs known to promote vascular aging that could explain its association with age advancement. However, it is unclear to us why other protease inhibitors did not show similar associations. 

Both CMV and hepatitis B may have promoted age advancement 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 aging and increased morbidity and mortality in both the general population and PLWH.

C360: What role did lifestyle play in the aging process?

Mr De Francesco: Our analyses did not find associations between smoking, alcohol consumption, or recreational drug use and age advancement, a result that may reflect both a genuine lack of association but could also reflect the limited statistical power and/or lack of direct information on underlying exposure to these factors. However, as we observed an increased age advancement in both PLWH and lifestyle-matched HIV-negative individuals, while blood donors appeared younger than their age, it is possible that unmeasured factors linked to lifestyle (ie, physical activity, sleep, or stress) may play an important role in the aging process. 

C360: What do your results mean for clinical practice? What can providers take away from your research? 

Mr De Francesco: Ideally, clinicians would want to intervene on those factors that appeared to be significantly associated with greater age advancement and for which an intervention is possible (eg, make sure that treatment for HIV at the same time covers appropriately the treatment of chronic hepatitis B). In addition, and more important, in clinical practice clinicians can provide support for the lifestyle and behavioral modifications to support a healthy lifestyle that are recommended for the general population. 

C360: What else do infectious disease specialists need to know about aging in patients with HIV?

Mr De Francesco: We believe that it is important to highlight that the association between age advancement and chronological age did not differ significantly between the 3 groups. While PLWH report a greater age advancement at study entry, they did not subsequently appear to age at an accelerated rate compared with the HIV-negative controls in the study, suggesting a static one-time hit attributable to HIV. This result is more suggestive of an accentuation rather than an acceleration of the aging process due to treated HIV disease.

Accentuated aging occurs when there is more age-related damage, but the year-on-year damage remains static over time; accelerated aging occurs when the decline arises earlier than expected and implies a progressive increase in the rate of decline. Our findings are consistent with studies of other age-related outcomes from the COBRA Collaboration2—while our findings should be interpreted cautiously, they should also be seen as a positive indication that PLWH who are successfully treated may not experience any further rapid age-related declines in their health.

References:

1. De Francesco D, Wilt FW, Bürkle A, et al; Co-morBidity in Relation to AIDS (COBRA) Collaboration. “Do people living with HIV experience greater age advancement than their HIV-negative counterparts?” AIDS. 2019;33(2):259-268. doi:10.1097/QAD.0000000000002063.
2. Cole JH, Underwood J, Caan MWA, et al. “Increased brain-predicted aging in treated HIV disease.” Neurology. 2017;88(14):1349-1357. https://doi.org/10.1212/WNL.0000000000003790.