publié le 10 novembre 2005
Edwin J. Bernard , Monday, September 05, 2005 A hidden epidemic of HIV infection may be occurring amongst older individuals, suggests Dr Nathalie Casau of the Albert Einstein College of Medicine, New York, in a review article examining HIV and ageing, published in the September 15 th issue of Clinical Infectious Diseases . In addition, the intersection of HIV, older age, and comorbidities like cardiovascular disease, osteoporosis and dementia require further research as the HIV population ages due the success of highly active antiretroviral therapy (HAART).
A hidden epidemic ? Between 10-13% of all HIV-positive individuals in the United States are aged over 50, and the number is expected to rise due to both new infections of older people, and the ageing HIV population who are living longer due to the success of anti-HIV therapies. Since doctors do not perceive older people to be at risk for HIV infection, they are less likely to undergo HIV testing, misdiagnosis is common, and HIV is diagnosed later in the course of HIV infection. One study of people aged 60-79 who had died in an old-people’s home with no history of HIV infection found that five percent were HIV antibody positive, although none of the deaths were directly caused by HIV infection.
Ageing and the immune system It first seemed - since there was a parallel between the natural immune-downregulation that occurs with ageing, and HIV-related immune dysfunction - that older HIV-positive individuals would progress more rapidly. When an older person is infected with HIV, CD4 T-cell loss is more pronounced compared with younger individuals, possibly due to a shrinking thymus, and it was thought that this may lead to a delayed immune response once HAART is begun. However, post-HAART studies have found similar increases in CD cell count, and more ’undetectable’ viral loads once HAART is initiated. This is thought to be due to older people being more likely to have better adherence to therapy than younger individuals. Studies have found that untreated, older HIV-positive individuals are twice as likely to die than their younger, untreated counterparts. However, it is striking that once older individuals have initiated HAART, after three months no significant differences in survival were seen. "These findings," writes Dr Casau, "suggest that deference of therapy or failure to diagnose HIV infection may have a more adverse impact on [older HIV-positive individuals’] survival, compared with younger HIV-infected individuals."
Tolerability and safety of HAART in older people There have been relatively few studies examining the tolerability and safety of antiretrovirals in older HIV-positive individuals. However, older age is associated with decreasing renal and hepatic function, and studies of AZT (zidovudine, Retrovir ) elimination (via the kidneys) found that it was substantially reduced in older individuals, resulting in toxic serum drug levels. Another study, comparing tolerability of protease inhibitors (PIs) in older versus younger people found that adverse events were much more common in older people (64% vs. 35% ; p=0.001) ; it was hypothesised by the study’s authors that decreases in albumin levels and liver function were related to the increased adverse events. "Prospective studies are needed to evaluate the appropriateness of current dosing of HAART in the elderly HIV-infected population," suggests Dr Casau.
Potential higher risk of drug-drug interactions Older age brings with it other health issues, and these comorbidities - cardiac, renal, hepatic, oncologic, neurological, and psychiatric - are often medicated, leading to a potential for a high risk of drug-drug interactions. One study of HIV-positive individuals over 55 found that 89% had comorbid conditions, and that 81% were taking non-HIV medication ; however, the study did not find a greater incidence of HAART-related side-effects. Nevertheless, Dr Casau adds that these comorbidities and interactions, "may be confounded by concurrent alcohol or drug abuse".
Menopause, and osteoporosis "Studies suggest that relatively few older HIV-infected women are receiving hormonal replacement therapy, despite data suggesting that it might be associated with decreased mortality in that population," writes Dr Casau. Osteopenia and osteoporosis are diagnosed more frequently both in older individuals and in younger HIV-positive individuals. This suggests that bone mineral density loss is greater older, HIV-positive individuals, although so far no studies have been undertaken in this population. "Additional studies that evaluate osteopenia and osteoporosis in the older HIV-infected population are needed," argues Dr Casau.
Dementia, and cardiovascular disease "Despite the well-known association between older age and increasing incidence of dementia, few studies have investigated the complex interactions between HIV infection, ageing, and neuropsychiatric diseases," writes Dr Casau, who notes that older age is associated with a more frequent diagnosis of HIV-related dementia as an individual’s first AIDS-defining condition. Similarly, evidence accrues that both HIV infection and HAART increase cardiovascular disease risk, and older age has long been associated with an increased risk of cardiovascular disease. "The metabolic toxicities of HAART and the proatherogenic state induced by chronic HIV infection may render older HIV-infected patients particularly vulnerable to accelerated atherosclerosis," Dr Casau suggests, "and may result in an increased risk of cardiovascular disease."
Dr Casau concludes that as more individuals are living and growing older with HIV, "age should be taken into consideration to optimize the care of older HIV-infected patients." She argues that more research is necessary to "better define age-related variations in expression of HIV/AIDS symptomology."
In addition, since both alcohol and drug abuse have been found to confound the effects of neurocognitive functioning in older HIV-positive individuals, "more research is essential to better measure and define neurological and psychiatric abnormalities in older HIV-infected substance abusers."
Reference Casau NC. Perspective on HIV infection and ageing : emerging research on the horizon. Clinical Infectious Diseases 41 : 855-863, 2005.