Who are the appropriate control subjects for studying HIV infection and aging?
The selected group should best fit the question being studied, to control for appropriate variables. For example, the Veterans Aging Cohort Study used a group of veterans with similar risk factors for HIV infection but who were not infected with HIV, to control for substance abuse, psychiatric illness, and other disorders that are common in veterans but not in the general population.
What are appropriate surrogate markers that predict outcomes in studies of HIV infection and aging?
These markers might differ significantly from the general population.
To what extent do normal aging processes result from viral infection and immune activation?
The similarities and differences in the processes underlying aging and chronic viral infection and how these processes influence each other remain to be determined, but connections among inflammation, immune activation, and disease should be explored. Furthermore, the role of chronic viral infections in immune senescence in the presence or absence of HIV infection should be a priority.
How do HIV infection and aging exacerbate each other?
Future research should define frailty and other age-associated events with enough specificity to provide early, easily attainable indices to allow the identification of frailty precursors in HIV-infected patients.
What are the age-associated differences in immunologic and virologic response to HAART and toxicities resulting from HAART?
Identifying particular antiretroviral drugs or treatment strategies that may be more effective in older HIV-infected individuals is essential.
What changes occur in the GALT with age?
Results from studies of HIV infection can inform new studies about the aging immune system within the gut and may provide information on a particularly significant subject, to examine the interaction between aging and HIV infection.
What are the biologic characteristics underlying age-associated fibrosis in multiple organ systems?
The triggers for fibrosis are not known, and it is not clear whether fibrosis observed during the course of HIV infection mirrors, overlaps with, or differs from that seen during aging.
What is the role of HIV- or HAART-associated mitochondrial toxicity in age-related illnesses in HIV-infected patients?
There are marked effects on mitochondrial function that are likely to be related to fatigue, comorbidities, and the frailty phenotype; HAART, particularly with nucleoside reverse-transcriptase inhibitors, may exacerbate these mechanisms.
Should the HIV treatment paradigm change for older patients?
It is not clear whether CD4+ T cell thresholds for management decisions should be different or whether correlates of immunologic success differ in older patients. Age-associated changes on pharmacokinetics and pharmacodynamics and how toxicities offset the benefit of the early initiation of HAART also should be explored. Although older adults consistently demonstrate greater adherence to HAART, compared with young adults, the occurrence of long-term adverse effects perhaps related to HAART (e.g., diabetes, atherosclerosis) suggests that the relative risks and benefits of starting HAART at an earlier threshold in older adults is an open question.
How can primary care screening and treatment guidelines be appropriately tailored to patients with HIV infection?
Future studies should explore whether choices among preventive measures (e.g., screening for cancer of the prostate or colon) can be informed by the likelihood of the patient living long enough to benefit from the intervention.
What can be learned regarding the management of complex chronic disease in patients aging with HIV infection, and how does this type of management differ from the management of single disease entities?
HIV infection could serve as a model of accelerated aging in a multiply comorbid patient that can be broadly applicable to geriatrics and gerontology. Training of additional researchers in geriatrics will facilitate integration of geriatric principles into infectious diseases research [175