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
[email protected]
June 2012
• 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]
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
Organ system
Condition / complication
Myocardial infarction
Primary lymphoma
HIV-associated neurocognitive disorder or
dementia (HAND or HAD)
Tuberculosis (pulmonary or extrapulmonary)
Pneumonia (recurrent, or Pneumocystis spp.)
Candidiasis (bronchi, trachea, lungs)
HIV-associated nephropathy (HIVAN)
Reduced bone mineral density
Invasive cervical cancer (oncogenic HPV)
Invasive anal cancer (oncogenic HPV)
Non-Hodgkin’s lymphoma, Kaposi’s sarcoma
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 agematched, 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
- Definition -
• Age-related changes in the
adaptive immune system that
are associated with increased
morbidity and mortality
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 proinflammatory in effector function
• This contributes to increased systemic
inflammation and collateral harm to
multiple organ systems
HIV-associated inflammation
and ‘immunosenescence’ have
been implicated as causally
related to the premature
onset of multiple end-organ
- Summary -
• HIV-associated immunosenescence
contributes to persistent
immunodeficiency and early onset of agerelated diseases
• Further investigation into these pathways
may lead to novel therapeutic
interventions useful in both HIV-infected
persons and in uninfected geriatric
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
HIV, Aging and
Increased Risks of
Malignant Diseases
Non-AIDS Related Cancers
• Higher cancer rates in long-term ARVtreated 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 HPVrelated malignancies
Kaposi’s Sarcoma
Functional Defects
Disorders [HAND]
and Dementia [HAD]:
A Hidden Epidemic ??
Neurocognitive Decline
• HIV-associated inflammation is believed
to be a major factor in comorbid CNS
• 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
The Graying of the
HIV/AIDS Epidemic
in the U.S.
[email protected]
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
US Landscape
EU Landscape
~50% of HIV+ persons are on ART
~50% of HIV+ persons are on ART
Patients in 1000's
Patients in 1000's
HIV Infected
In Care
On Antiretroviral
1. Available at Accessed August 2010.
2. Synovate Healthcare U.S. HIV Monitor Q2 2010
HIV Infected
1. National Surveillance Units per Country and ECDC Accessed 1Q 2010
2. IMS/GERS & Synovate 2Q 2010
In Care
On Antiretroviral
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

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