Ageing with HIV infection

Victoria Hall1, Matthew Skinner2, Jennifer Hoy3,4

  1. Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC

  2. Department of Infectious Diseases, Sir Charles Gairdner Hospital, Perth, WA

  3. Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC

  4. Monash University, Melbourne, VIC


The average age of people with HIV infection in Australia has increased substantially since 1986, due predominantly to the availability of combination antiretroviral therapy (ART), associated with improved survival and reduction in AIDS-related complications.[1-6] Non-AIDS related mortality has now surpassed AIDS-related mortality as the major cause of death in people with HIV infection. [4] In 2017 in Australia, 46% of people with HIV infection were aged over 50 years, reflecting a global trend of prolonged survival and late acquisition of HIV infection among older people. [2, 6]

Despite increasing longevity, ART has not enabled a complete return to normal health among older people with HIV, who have a well-recognised increased burden of non-communicable age-associated comorbidities. [1-4, 6-8] The pathogenesis of these conditions in this setting may involve an accelerated (premature, faster) and/or accentuated (more frequent) ageing process related to a burden of harmful lifestyle behaviours and their effects, such as smoking and central fat accumulation; effects of persistent HIV infection in cellular reservoirs; increased permeability of the gut to microbial products and alterations in the gut microbiome; ART toxicity, and co-infection with cytomegalovirus or hepatitis C virus (HCV). [1, 3, 5, 6, 8-11] Many of these factors contribute to HIV-associated immune activation and chronic inflammation, which, while blunted by ART, are not eliminated. In particular, activation of innate immune responses has been implicated in non-AIDS co-morbidities, and when observed in older people, is described as ‘inflammaging.’ [9] [1] [3-5, 7, 10] [11] In spite of this, there is clear evidence of benefit for early ART in all people with HIV infection to help reduce chronic inflammation. [10]

Subclinical chronic inflammation associated with HIV infection and its relationship with age-related complications and decreased survival has evolved as a top priority in the HIV research agenda. [4, 5] Specifically, data from the Strategies for Management of Antiretroviral Therapy Study (SMART study) demonstrated that elevated plasma levels of IL-6 and D-dimer were strongly related with non-AIDS-defining co-morbidities and all-cause mortality in patients on ART. [5] [12] The concept of immunosenescence, ‘a functional limitation of immunity resulting from age-associated changes in a variety of cells involved in both innate and adaptive immunity, and an imbalance between the two arms, describes a similar immune senescent phenotype and T-cell abnormalities common to both ageing in the general population and untreated HIV infection. [5]

This complex interplay of factors has been associated with an increase in the number of people with HIV infection who are also living with co-morbidities. [6, 13, 14] These co-morbidities include, but are not limited to, neurocognitive disorders, cardiovascular disease (CVD), chronic kidney disease (CKD), metabolic syndrome, type 2 diabetes mellitus, osteoporosis and cancers. [9] [3, 7, 8] [4, 5] [6] The accumulation of these co-morbidities in multiple systems has led to a rising incidence of geriatric syndromes in older people with HIV infection, including multimorbidity and polypharmacy, delirium, frailty, incontinence, falls and fragility fractures, and cognitive dysfunction, further compromising quality of life and often occurring much earlier in comparison to HIV-negative counterparts. [9] [3-5, 7, 8]

The rate of ageing can differ significantly between individuals, dependent upon both genetic and environmental factors. [15] The Australian Bureau of Statistics defines age chronologically; hence persons aged over 65 years are classified as ‘older.’ [16] Chronological age however may not be the most accurate way of measuring ageing or predict an individual’s trajectory and total lifespan. [17, 18] To address this inadequacy, the notion of ‘biological age’, which encompasses the use of biomarkers to describe age-related changes in body function and composition, has been developed, and helps predict the onset of age-related morbidity and/or mortality.[17] [7]  A number of biomarkers have been proposed to investigate the association between HIV infection and ageing and include plasma biomarkers of chronic immune activation, inflammation and hypercoagulation; decreased chromosome telomere length; increased mitochondrial DNA somatic mutations; ophthalmological parameters; and age-related brain atrophy. [1] [3, 6] [11] [19] [20-26] Telomere shortening in people with HIV infection has been attributed to the effects of the virus itself as well as exposure to some nucleoside analogue reverse transcriptase inhibitors (NRTIs). [1]

With the average age of those attending HIV clinics increasing, and with this expected to continue into the future, along with the burden and complexity of non-communicable co-morbidities, healthcare needs and associated costs are expected to increase. [6] Guidelines to help direct the optimal clinical management of older people with HIV infection are therefore likely have a positive impact on the health system. [4] A recently convened workshop on HIV and ageing emphasised the importance of instituting holistic comprehensive care for people ageing with HIV infection, that not only includes HIV care, but also management of the many other psychosocial, mental health and co-morbid medical issues contributing to reductions in quality of life. [27] Suggested approaches include behavioural and cognitive diagnostic screens and educational activities on topics such as smoking cessation and cardiovascular health. [27] Social interaction was also highlighted, given the overwhelming isolation that people with HIV infection experience, related to persistent stigma associated with HIV infection and ‘HIV survival fatigue.’ [27] Social engagement and interaction with other people with HIV infection may help to address this. A recent National HIV, Ageing and Quality of Life Roundtable (2019) highlighted similar findings and stressed the importance of improvement in geriatric models of care for people with HIV infection, support for Aged Care Services (including My Aged Care and National Disability Insurance Scheme) to meet the needs of diverse groups of individuals, elimination of both perceived and actual stigma and discrimination through peer educators and advocates, and continued HIV education for the revolving door of aged care workers.