HIV and Aging

Abstract

HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to anti-retroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to > 70 years of age. Biologic, medical, individual social and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups’ findings and recommendations are summarized in this report. Key overarching themes identified by the group included: multi-morbidity, poly-pharmacy and the need to emphasize maintenance of function; the complexity of assessing HIV vs. treatment effects vs. aging vs. concurrent disease; the inter-related mechanisms of immune senescence, inflammation and hypercoagulability; the utility of multi-variable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures and multi-morbidity, as well as facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

“…Possible explanations for a higher mortality risk in older patients include multi‐morbidities, polypharmacy, chronic infection with viral pathogens (e.g. CMV), lower CD4/CD8 ratio, or other age‐related factors, as well as an increased risk of AIDS‐related complications given poor immunologic recovery despite ART 1, 9. A recent study by Edwards et al .…”

“…Older people may have an inaccurate perception of the risk for HIV infection in their peer group and less frequent discussions with medical providers regarding sexual practices and drug use 6, 7, 8. Finally, age‐related changes in the reproductive tract and immune system may enhance susceptibility to HIV acquisition 1, 9.…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…An increased number of studies draw the attention to the reduction in telomerase length, which is a measure of the proliferation of each single cell, and to mitochondrial damage, which is able to increase oxidative stress and inflammatory pattern, as major drivers for senescence program in all individuals. 7,8,13 Senescence provokes a cascade of morphological and phenotypic changes in cells: a) increase in size and a flat morphology; b) upregulation of tumor suppressor genes and downregulation of cell-cycle promoting genes; c) production of senescence-associated secretory phenotype (SASP), which are inflammatory cytokines, growth factors and matrix metalloproteinases. 8,10,11 In particular Effros et al 8 found an increase in pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor-a [TNF-a]) and a reduction in antiviral interferon-g (IFNg) (released by CD8C T-cells).…”

“…16 The higher level of inflammation in HIV individuals is measured by inflammatory biomarkers: in particular interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer (DD), cystatin C-dimers and cystatin D-dimers. 7,13,[17][18][19] In HIVinfected individuals these biomarkers are higher than in uninfected adults. They have been studied in HIV patients during HAART and they remain elevated Adapted by permission of James L. Kirkland.…”

“…9 despite suppressive therapy; 7,18 moreover in SMART study IL-6 and DD values predicted both mortality and non-AIDS related events in HIV patients. 13,18 Numerous factors are involved in the persistence of inflammation during HIV infection: a) ongoing HIV production; b) viral coinfections and microbial translocation; c) loss of T-regulatory cells; d) irreversible fibrosis of the thymus and lymphoid tissues and e) oxidative stress from smoking, obesity and HAART toxicities. 7,13 In spite of the benefit in survival due to HAART, event therapy itself may contribute to cellular activation and senescence.…”