August 2008

Workshop on HIV Infection and Aging: What Is Known and Future Research Directions
Effros RB, et al. Clin Infect Dis 2008;47:542-553. [PubMed Abstract]

Background: There are certain common features of aging and HIV infection, including the observation that aging strongly influences the course of HIV. This is shown by the increased likelihood of HIV seroconversion (JAIDS 2007;45:85), the time from HIV infection to AIDS in the absence of HAART is shorter (Am J Epidmiol 1994;140:747), and both conditions are associated with accelerated rates of cirrhosis, cardiovascular disease, renal disease, and cancer (JID 2008;197:1133). As a result of these similarities, a group of researchers representing infectious diseases, geriatrics, immunology, and gerontology reviewed the state-of-the-art HIV infection and aging data to identify appropriate background information and define priorities for future research. The meeting was sponsored by the Association of Specialty Professors (ASP), the IDSA, the National Institute on Aging and NIAID. The following is a summary of some of the observations reviewed:

Host Defenses: The review indicated marked similarities, but some differences. Similarities included decreases in the B cell repertoire and decline in primary B cell response with reduced antibody response. However, the major effects are on T cells and thymus function. Both aging and HIV infection show T cells to be hyporesponsive, including reduced CD8 cells.

Mucosal immunity: This is obviously affected very early in the course of HIV infection with the assault on gut-associated lymphoid tissue (GALT), but the effects of aging on this aspect of gut immunity is not known.

Immunity and Chronic Infection: The best correlation is probably with varicella-zoster virus (VZV) reactivation which increases substantially with both aging and HIV infection.

Response to HAART: It is noted that older patients have a less impressive CD4 cell response to HAART compared to younger patients, although the results are somewhat variable (JAID 2001;183:1290).

Functional Complications: Both groups are subject to increased rates of frailty. The cause is unknown, but possibly related to immune activation and expressed as elevated levels of CRP, D-dimer, IL-6, etc. (Arch Intern Med 2002;162:233). Both groups appear prone to cardiovascular disease, renal disease, liver disease, and cancer, including solid-tissue tumors.

Some of these comparisons with correlation and discordance are shown in the following Table:

*NI=Normal

Conclusions: The authors conclude with multiple research priorities to address some of the issues, but possibly the most important contemporary issue is the impact of aging on recommendations of “when to start” HAART based on more rapid progression of HIV on older patients but also the effect of HIV replication in making younger patients age faster.