The Graying of the HIV/AIDS Epidemic in the U.S.

Effects of Aging on the Course of HIV Infection - and Vice Versa - James R. Minor, Pharm.D CAPT, USPHS, Retired jminor101422@gmail.com 919-641-2856 June 2012

Disclaimer

Objectives Describe the clinical issues affecting older HIV+ patients Describe ‘immunosenescence’ and its impact on the course of HIV infection in older patients Summarize HIV-associated, non-AIDS conditions and co-morbidities

HIV/AIDS in Older Persons [50 years of age or older]

Persons 50 years of age+ account for: The Numbers [US] Persons 50 years of age+ account for: 15% of all new HIV infections/year 20% of all new AIDS diagnoses 35% of all deaths due to AIDS 25% of persons living with AIDS [up from 17% in 2001]

Common AIDS and Non-AIDS Complications Organ system Condition / complication AIDS-defining Non-AIDS-defining Cardiovascular Cardiomyopathy √ Myocardial infarction Nervous Toxoplasmosis Primary lymphoma HIV-associated neurocognitive disorder or dementia (HAND or HAD) Pulmonary Tuberculosis (pulmonary or extrapulmonary) Pneumonia (recurrent, or Pneumocystis spp.) Candidiasis (bronchi, trachea, lungs) Renal HIV-associated nephropathy (HIVAN) Bone Reduced bone mineral density Malignancies Invasive cervical cancer (oncogenic HPV) Invasive anal cancer (oncogenic HPV) Non-Hodgkin’s lymphoma, Kaposi’s sarcoma Transition: There are many serious conditions that commonly affect people living with HIV, and not all will result in an AIDS diagnosis, although some certainly can be life-threatening. Main message: Initiation of at higher CD4 counts might help prevent or stall the development of AIDS-defining and perhaps non-AIDS-defining conditions. Background: The incidence of some non-AIDS-defining complications (eg, certain types of malignancies, such as lung cancer or anal cancer; CV disease) has been increasing in recent years as HIV-infected patients live longer. This is one of the reasons that HIV treatment guidelines have shifted towards suggesting that ART be initiated at higher CD4 counts, rather than waiting until the immune system or other organ systems sustain potentially irrevocable damage.

HIV+ persons have a substantially shortened life span, largely due to increased risks of ‘non-AIDS’ complications and comorbid diseases : renal, bone, metabolic, liver, malignant diseases, and neurocognitive decline

Risk of non-AIDS morbidity is higher among ARV-treated HIV+ individuals than in their age-matched, uninfected peers for reasons directly related to the disease or its treatment

All these degenerative comorbid diseases have a negative impact on overall functioning and Quality of Life, and are thought to be related to accelerated or premature aging

‘Immunosenescence’

‘Immunosenescence’ - Definition - Age-related changes in the adaptive immune system that are associated with increased morbidity and mortality “Adaptive” vs. “Innate” immunity

‘Immunosenescence’ Adaptive immune system changes with aging: Decreased number and function of hematopoietic stem cells Thymic dysfunction, involution Decreased circulating naïve T cells Decreased CD4/CD8 ratios Increased proinflammatory cytokines: IL-6, TNFα, CRP, cystatin C Increased pools of senescent CD28- ‘memory’ cells *

Senescent T Cells With aging or in the presence of chronic viral infection, CD28- T cells become resistant to apoptosis and become pro-inflammatory in effector function This contributes to increased systemic inflammation and collateral harm to multiple organ systems Compare apoptosis to auto mechanics

HIV-associated inflammation and ‘immunosenescence’ have been implicated as causally related to the premature onset of multiple end-organ diseases

‘Immunosenescence’ - Summary - HIV-associated immunosenescence contributes to persistent immunodeficiency and early onset of age-related diseases Further investigation into these pathways may lead to novel therapeutic interventions useful in both HIV-infected persons and in uninfected geriatric populations

Prevention and Public Health Challenges in Older HIV+ Persons Many older persons are sexually active but may not be practicing safer sex Older women are at higher risk due to age-related genital changes Many older persons may know less about HIV/AIDS and less likely to protect themselves or to get tested Discrimination and stigma facing older HIV+ may delay testing, diagnosis and entry in treatment

HIV and Aging: Overall Framework

Renal Disease

Renal Disease Untreated HIV disease [persistent viral replication] is associated with higher risks of kidney disease – suggesting that HIV replication directly or indirectly affects the kidneys Many antiretroviral agents [ARVs] are also nephrotoxic

Bone Disease

Bone Disease Prevalence of osteopenia and osteoporosis is at least 3x greater in HIV+ subjects than in HIV uninfected controls Persistent inflammation is probably causally related to bone disease, as many biomarkers of inflammatory bone disease are higher in HIV disease [IL-6, TNF… ] Other contributory factors: ART, vitamin D deficiency

Some factors non-modifiable, others are modifiable

Metabolic and Cardiovascular Complications

HIV, Aging and Increased Risks of Malignant Diseases

Non-AIDS Related Cancers Higher cancer rates in long-term ARV-treated patients is strongly related to the degree of immunodeficiency HIV-associated immune deficiency may be the primary factor driving an excess risk of many non-AIDS cancers Increasing prevalence 0f HCV- and HPV- related malignancies

Covers decade from 1992 to 2003

Kaposi’s Sarcoma

Neurocognitive Functional Defects

HIV-Associated Neurocognitive Disorders [HAND] and Dementia [HAD]: A Hidden Epidemic ??

Neurocognitive Decline HIV-associated inflammation is believed to be a major factor in comorbid CNS disease Debate: Is ongoing CNS disease due to inadequate CNS penetration of ARVs [allowing ongoing viral replication] OR to residual, low-grade inflammation ??

HIV and Aging: Overall Framework

The ‘double insult’ of aging and HIV infection to the hematopoietic system can contribute to many of the factors associated with immunosenescence: chronic inflammation, reduced ability of the immune system to mount effective response to infections, vaccines, other stressors

Novel therapeutic strategies aimed at preventing or reversing immunologic defects and changes related to immunosenescence will be necessary if HIV-infected patients are to achieve normal life spans

COSTS related to the Graying of America – general and in particular HIV/AIDS-related !!!

Advances of modern medicine – people living longer, pursuing active lifestyles, dealing with attendant age-related health issues

Washington Post, circa 1986

Acknowledgements Category Day Organizers, Fellow HCP’s in and out of PHS Uniform, CPO, JO’s, Students and Residents, PATIENTS Category Awardees. Wear uniform with Pride and Distinction, Speak, Publish !!

The Graying of the HIV/AIDS Epidemic in the U. S. jminor101422@gmail The Graying of the HIV/AIDS Epidemic in the U.S. jminor101422@gmail.com

Linkage to Care - US and EU There are still a significant number of patients who are undiagnosed, not linked into care and not on therapy

Keys to Achieving Long-Term Objective of Ending the HIV/AIDS Pandemic * Efficiently identify greater numbers of HIV+ people earlier in the course of disease through expanded voluntary HIV testing programs, and link them to appropriate care and antiretroviral treatment Find innovative approaches to curing HIV/AIDS by eradicating or permanently suppressing the virus in infected people, thereby eliminating the need for lifelong antiretroviral therapy Scale-up implementation of proven HIV prevention strategies, develop additional effective prevention strategies, such as a vaccine, and build on current successes in pre-exposure prophylaxis, microbicides and ‘treatment-as-prevention’ to achieve a sustainable and comprehensive, combination HIV prevention strategy * NIH/NIAID, 31 May 2011

“HIV testing should be the fifth vital sign” Carl Dieffenbach, Director, DAIDS, NIAID 1 June 2011

HIV Prevention – Recent Milestones - Two populations are disproportionately affected by HIV Men who have sex with men (MSMs) Women - nearly half of the adults living with HIV. CAPRISA-004: 39% reduction in new HIV infections in women with the use of topical 1% Tenofovir gel; first trial to prove efficacy of PrEP iPrEx: 44% reduction in new infections when TDF/FTC was used daily as pre-exposure prophylaxis (PrEP) in MSMs