Individuals aged > 50 years have emerged as a significant and fast-growing segment of the HIV positive population. HIV patients > 50 years now comprise 10%-13% of all HIV positive persons in the United States, according to Nathalie Casau, MD, of Albert Einstein College of Medicine, Bronx, New York. Dr. Casau reviews the relationship between aging and HIV infection in the US in  the September 15, 2005 issue of Clinical Infectious Diseases [1].

The Hidden Epidemic

The increasing prevalence of HIV positive individuals aged >50 years stems from increased survival rates among this population and from delayed diagnosis of older persons with HIV, according to Dr. Casau.

There are several reasons for the underreporting of older HIV positive individuals. First, physicians often do not regard their aging patients as being at risk for HIV compared to younger persons, and as a result, do not recommend HIV testing to them. In other cases, some of the symptoms of HIV infection are misdiagnosed by physicians. Finally, persons aged >/= 50 years may receive an HIV diagnosis much later in their disease course than do younger individuals with HIV disease.

The Influence of Age on Immune Function

There is a prevailing consensus regarding HIV disease, immunity and age that HIV-associated immune dysfunction parallels age-related immune down-regulation. For example, aging is associated with decreased production of interleukin 2 (IL-2) and IL-2 receptors [2,3] that in turn adversely affects T cell function.

Further, a greater number of naïve CD4 T cells in older HIV patients are depleted than among younger patients, a situation that may lead to a delayed immune response to HIV. Other researchers find a relation between older age, decreased thymus activity and reduced CD4 cell response to HIV. They believe that older HIV patients may not mount as potent an increase compared to their younger counterparts.

Previously, researchers documented that persons aged >50 generally experienced a more rapid progression to AIDS and lower survival rates following AIDS diagnosis. In the HAART era, studies also have documented that older HIV patients experience a delay in immune recovery.

However, Dr. Casau suggests that more recent studies of older HIV patients and their response to HAART seem to refute all these findings. She points out that Tumbarello et al. [4] compared responses to HAART in younger and older HIV-infected patients and did not observe age-related differences in viral suppression, immune recovery, or clinical outcome, despite the presence of comorbid conditions in the older age groups.

Further, Dr Casau notes a study of 101 older HIV-infected patients matched with 202 younger HIV-infected patients by Fair Wellons et al. [5]. In this study the authors conclude, “Although HIV-infected patients aged >/=50 years had increases in the CD4 cell count that were similar to those in younger HIV-infected patients, a greater proportion of older patients attained an undetectable HIV RNA level, compared with the younger group (11% vs 26%; P = .01).” Increased adherence to therapy among the older HIV patients could also explain these outcomes, because older patients are more likely to be compliant than are younger patients.

The most compelling refutation of the early data on outcomes in older vs younger patients concerns the data on mortality. In a retrospective cohort study, Perez et al. [6] compare mortality rates for 253 HIV-infected individuals aged >/= 50 years and for 535 younger HIV-infected patients. Older HIV positive individuals who were not receiving HAART had twice the hazard rate for death than younger, untreated HIV positive individuals.

Dr. Casau believes these findings suggest that “deference of therapy or failure to diagnose HIV infection in older individuals may have a more adverse impact on their survival, compared with younger HIV-infected individuals.” After initiation of HAART, older patients had a >2-fold reduction in the hazard rate for death and a 72% reduction in mortality. Dr. Casau notes, “After 3 months, there were no statistically or clinically significant differences in the survival rate between the treated younger and older HIV-infected groups.”

Tolerability and Safety of HAART in Older Patients

Various non-HIV-related illnesses frequently affect many older HIV patients, including cardiovascular, renal, hepatic, oncologic, neurologic, and psychiatric conditions. As a result of these illnesses, older patients must take a variety of medications other than HIV drugs. This situation can lead to potentially harmful drug-drug interactions in older HIV-infected patients who are concurrently on HAART.

Little prospective research on the toxicity of HAART has been focused on the geriatric population, reports Dr. Casau.

Pharmacology of Antiretrovirals in Older Patients

Most clinical studies of new, experimental anti-HIV drugs exclude older HIV patients and/or those with a comorbid condition. Other studies may enroll older patients, but do not design the studies in a manner that allows for a comparison of the data between older and younger patients.

There are scant data on the appropriateness of current dosing of HAART in the elderly HIV population. It in not yet known whether pharmacokinetic parameters differ significantly among older patients. Dr. Casau calls for implementation of studies that will either make age-dependent modifications in dosing recommendations or develop other strategic approaches for this unique population.

Neurocognitive Research on HIV and Aging

HIV does not appear to contribute directly to the pathogenesis of HIV dementia. Researchers have suggested that neuronal damage is indirectly caused by cytokines.

The multicenter trial of the AIDS Clinical Trials Group (ACTG 5090) is investigating selegiline, a treatment of Parkinson disease, as therapy for cognitive impairment associated with HIV infection. Although the association of aging and dementia is well known, few studies have investigated the complex interactions between HIV infection, aging, and neuropsychiatric diseases.

The presence of HIV-associated dementia as the first AIDS-defining diagnosis is associated with older age in HIV-infected patients. There is also emerging data concerning the effects of concurrent alcohol or drug abuse among older patients.

HIV, Aging and Cardiovascular Disease

Bozzette et al. [7] studied the risk of cardiovascular and cerebrovascular disease among 36,766 HIV-infected patients who were receiving antiretrovirals. Ten percent of this cohort was aged >55 years. In this retrospective study, there was no increase in cardiovascular or cerebrovascular mortality directly attributable to antiretrovirals.

Summary and Future Directions  

Due to the increase of HIV positive individuals who are living and growing older, it is important to consider age when formulating optimized care for this group.

“Limited data are available on the safety and tolerability of HAART in this population, and psychiatric and neurocognitive diseases also endanger the survival and the quality of life for older HIV-infected individuals,” according to Dr. Casau. “Emerging evidence suggests that metabolic, neuropsychiatric, and cardiovascular morbidities could be exacerbated by use of antiretrovirals or by HIV infection itself,” she writes.

Zingmond et al. [8] found significant variations in symptoms between older and younger HIV-infected patients. “More research is necessary to better define age-related variations in the expression of HIV/AIDS symptomatology,” notes Dr. Casau.

Commentary by Ronald Baker, PhD

Clearly, more research is required to determine a standard of care for older patients living with HIV infection and AIDS. It is unacceptable that so many important questions about treatment and care for this already sizeable and continuously expanding HIV patient population remain unanswered.

It will be up to policy makers, including AIDS treatment advocates, physician groups, and the Department of Health and Human Services, to lobby both the drug companies and the FDA to make research on older HIV patients a priority, as has been done for other, traditionally underserved groups such as women, children, IV drug users, and African Americans.

It would also be appropriate for the NIAID, the FDA and other policy groups to jointly sponsor a consensus conference focused on developing a blueprint for how best to address the needs of older HIV patients within the framework of AIDS clinical trials.

09/07/05

References

1.       N C Casau. Perspective on HIV Infection and Aging: Emerging Research on the Horizon. Clinical Infectious Diseases 41(6): 855-863. September 15, 2005.

2.       F Fagnoni and others. Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95:2860-2868. 2000.

3.       H Valdez and others. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS 16:1859-1866. 2002.

4.       M Tumbarello and others. Older HIV-positive patients in the era of highly active antiretroviral therapy: changing of a scenario. AIDS 17:128-130. 2003.

5.       M Fair Wellons and others. HIV infection: treatment outcomes in older and younger adults. Journal of the American Geriatric Society 50:603-607. 2002.

6.       J L Perez and R D Moore. Greater effect of highly active antiretroviral therapy on survival in people aged 50 years compared with younger people in an urban observational cohort. Clinical Infectious Diseases 36:212-218. 2003.

7.       S A Bozzette and others. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. New England Journal of Medicine 348:702-710. 2003.

8.       D S Zingmond and others. Differences in symptom expression in older HIV-positive patients: the Veterans Aging Cohort 3 Site Study and HIV Cost and Service Utilization Study experience. Journal of Acquired Immune Deficiency Syndromes 33 (Suppl 2):S84-92. 2003.