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HIV infection acquired at older age is associated with
more rapid HIV disease progression
CASCADE, Lancet 2000Progression to CDC stage C by age at seroconversion, before introduction of HAART
100
75
50
25
0
Proportion developing AIDS (%)
0 5 10 15
Time since seroconversion (years)
<55–14 15–2425–3435–4445–5455–64≥65
Age (years)
UK CHIC: Life expectancy according to CD4 count compared to the general population
*People who started ART in 2000–8 by CD4 cell count group atstart of ART compared with that of UK population (2000–6 women and men)
60
50
40
30
20
10
Life expectancy (years)
20 25 30 35 40 45 50 55 60 65Age (years)
Female UK
Male UK
CD4 200–350*
CD4 100–199*
CD4 <100*
70
May et al, BMJ 2011
With permission from the Health Protection Agency, 2011
New HIV diagnoses among adults ≥50 years
200020012002200320042005200620072008200920102011(to June)
70+60–6950–59
0
100
200
300
400
500
600
700
800
900
Numbers diagnosed
Smith et al, AIDS 2010
High rates of late diagnosis among adults ≥50 years in the UK
0
10
20
30
40
50
60
70
Percentage diagnosed late
≥50 years 15–49 years
Overall
48%
33%
MSM
40%
21%
Heterosexualmale
53%
45%
Heterosexualfemale
51%
36%
Other
58%
33%
Smith et al, AIDS 2010
Short-term (6 months) mortality is higher among adults ≥50 years with a late diagnosis
02468
12
16
20
Numbers diagnosed (%)
Prompt diagnosis
Late diagnosis
2000
10
14
18
2001 2002 2003 2004 2005 2006 2007
7
Significance of age at diagnosis
• HIV testing is often delayed in older individuals1 – Older individuals may not perceive themselves as being
at risk for HIV infection – HCPs may fail to consider HIV as a potential cause of
illness• Delayed treatment and diagnosis may have more adverse
consequences in older individuals compared with younger people2,3
• However, older patients derive a similar level of benefit form ART as younger patients4
1. Rotily M et al (2000) Int J STD AIDS 2. Kirk (2006) J Am Geriatr Soc
3. COHERE Study Group (2008) AIDS 4. Perez JL et al (2003) Clin Infect Dis
FDA meta-analysis: age differences in the response to initial HAART in women
• CD4 cell count improvementCD4 Overall: consistently no significant difference– NRTI/PI group: consistently no significant
difference– NRTI/NNRTI group: greater improvement in
women ≤ 35 years consistently significant or nearly significant
• HIV-1 RNA viral suppression (< 400 copies at week 24)– Overall and both drug class groups: consistently
significantly greater success in women ≥ 50 years
1. Yan et al. IWHW 2013, oral presentation 19.
Datasets: registrational ART trials submitted to the FDA in 2000–2010: 4414 HIV-infected naive women, 32 RCTs, 66 study arms Methods: Meta-analysis on age group (≤ 35 vs ≥ 50) differences in week 24/48 responses in virologic (HIV-RNA < 400 c/mL) and immunological measures (CD4 count change from baseline)
2013 2039
HIV and ageing
Adapted from Deeks SG, Phillips AN. Br Med J 2009
Normal ageing
(average age in many
clinics now around 50)
Lifestyle risk
factors(smoking, drug and
alcohol use)
Drug toxicity
(for example tenofovir and renal disease)
Persistentimmune
dysfunction andinflammation
? Prematureageing
11
Onset of early menopause in women with HIV
26%
10%
0%
5%
10%
15%
20%
25%
30%
HIV infected HIV uninfected% o
f w
om
en e
xperiencin
g e
arly
onset of m
enopause (<40 y
ears
)
11
P=0.04
Schoenbaum et al (2005) Clin Infect Dis
• Women living with HIV were 73% more likely to experience early onset of menopause, compared with HIV-uninfected women (P=0.024)
n=303 n=268
12
Potential contributors to early onset of menopause in women with HIV
Smoking Socioeconomic status
Menopause can occur up to 1–2 years earlier in
smokers, compared with non-smokers
Markers of low socioeconomic
status (e.g. lower level of
education, unemployment and poverty)
have been associated with
early menopause onset
Lower CD4+ count has been associated with
early menopause onset
Immunosuppression
13
The menopause• The menopause is marked by the ending of
menstruation and ovulation– Falling levels of the female sex hormone, oestrogen
• Onset of the menopause is associated with an increased risk of:– cardiovascular disease (CVD)– diabetes – osteopenia / osteoporosis
• Early onset menopause (before 46 years):– increases the risk of these diseases– may be linked to increased mortality
14
Managing the menopause in women with HIV
• Strategies to offset effects associated with menopause include:– Healthy lifestyle choices
– Smoking cessation
– Adherence to effective ART
– HRT
– Symptom management
– Alternative therapies
Hormone replacement therapy in women living with HIV
• HRT may be useful for some women with HIV
• Risks may outweigh the benefits if they: – smoke
– are overweight
– have had blood clots, breast cancer, diabetes, high cholesterol levels, liver problems, or a family history of heart disease
• Oestrogen and/or progesterone have been shown to interact with many HIV drugs
15
16
Consequences of ageing as a woman with HIV
• Women living with HIV face all the challenges that the general population faces when growing older PLUS:
16
Conditions with increased incidence in women living with HIV:
• Hormonal changes• Cardiovascular events• Non-AIDS-defining
infections• Renal disease• Non-AIDS-defining
cancers/malignancy• Muscular and skeletal
changes• Non-AIDS-dementias,
neurocognitive changes, mood and CNS disorders
The consequences of living longer
with HIV
The consequences of longer exposure to HIV treatment
regimens
Co-morbidities in HIV
1. Clifford, Top HIV Med 2008; 2. Brown et al, J Clin Endocrinol Metab. 2004; 3. Triant et al, J Clin Endocrinol Metab 2007; 4. Gupta et al, Clin Infect Dis 2005; 5. Patel et al, Ann Intern Med 2008 6. Terzian et al, J Women’s Health 2009
Reduced bone mineral densityIncreased prevalence of osteoporosis or osteopenia in spine, hip or forearm:63% of HIV+ patients2
Neurocognitive dysfunctionNeurological impairment present in ≥50% HIV+ patients1
Cardiovasculardisease75% increase in risk of acute MI3
Renal dysfunctionSome HIV+ patients have abnormal kidney function4
FrailtyIncreased frailty phenotype in HIV; Associated with CD4 count6
CancerIncreased risk of non-AIDS-defining cancerse.g. anal, vaginal, liver, lung, melanoma, leukemia, colorectal and renal5
Co-morbidities
Reduced bone mineral
density
Emotional challenges
Cardiovasculardisease
Renal dysfunction
Cancer
Risk factors for decreased bone mineral density in women
• Female sex
• White race
• Family history
• Increasing age
• Amenorrhoea/premature menopause
• Decreased physical activity
• Smoking
• Alcohol
• Decreased bone acquisition
Classic
HAART-related
• Nucleoside analogues /mitochondrial dysfunction
• Protease inhibitors• Lipodystrophy
HIV-related
• Cytokines (e.g. TNFa, IL6)
• Decreased muscle mass
• Decreased fat mass
• Fat deposition in marrow
• Chronic diseases (e.g. hyperthyroidism, hyperparathyroidism, liver
disease, rheumatological conditions, eating disorders, etc.)
• Hypogonadism
• Renal dysfunction
• Malnutrition/low BMI
• Medications (e.g. corticosteroids, anticonvulsants, anticoagulants)
Secondary
Adapted from Glesby, 2003 Clin Infect Dis
Prevalence of osteoporosis in HIV+ patients vs HIV- controls: a meta-analysis
Brown & Qaqish, AIDS 2006
• Overall prevalence of osteoporosis in people living with HIV: 15%
Odds ratio.01 1 100
Amiel (2004)Brown (2004)Bruera (2003)Dolan (2004)
Huang (2002)Knobel (2001)
Loiseau-Peres (2002)Madeddu (2004)
Tebas (2000)Teichman (2003)
Yin (2005)
Overall (95% CI)
5.03 (1.47,17.27)4.26 (0.22,82.64)4.51 (0.26,79.27)2.11 (0.54,8.28)3.52 (0.15,81.92)5.13 (1.80,14.60)4.28 (0.46,39.81)29.84 (1.80,494.92)3.40 (0.19,61.67)17.41 (0.97,313.73)2.37 (1.09,5.16)
3.68 (2.31,5.84)
Study Odds ratio
(95% CI)
• Prevalence of osteoporosis is estimated to be approximately 3-fold higher in those living with HIV, than HIV- individuals
Increased fractures in women living with HIV
Fracture prevalence in women/100 persons
Healthcare registry study:• 8,525 HIV-positive patients• 2,208,792 HIV-negative patients
Overall comparison p=0.002
HIV+
HIV-
30–39 40–49 50–59 60–69 70–79
Years
7
6
5
4
3
2
1
0
Triant et al, J Clin Endocrinol Metab 2008
Switch from Tenofovir to Abacavir and BMD Change: Multicenter RCT (Abs:824)
• 54 patients on TDF regimen for at leats12 months suppressed VL• Patients have loss of BMD (DEXA)• Switched to ABC (n=26) and continued with TDF (n=28)• Significant improvement in BMD particularly at femur in ABC arm
BMD Changes at 48 weeks
WIHS: vitamin D insufficiency may impair CD4 recovery among participants with advanced disease on HAART
• Substudy of 204 HIV-infected women with advanced disease (CD4 < 200 cells/μL), who started HAART after enrolment in the Women’s Interagency HIV Study (WIHS)
• Majority were non-Hispanic black (60%) and had insufficient vitamin D levels (89%)
• In adjusted analyses, at 24 months after HAART, insufficient vitamin D (OR 0.20, 95% CI 0.05–0.83) was associated with decreased odds of CD4 recovery
• Average immune reconstitution attenuated significantly (p < 0.01) over time among those with insufficient vitamin D levels compared with those with sufficient vitamin D levels
Aziz et al. AIDS 2013;27:573–78.
Mean CD4 count (cells/mL) among women with normal (> 30 ng/mL) and insufficient or deficient vitamin D (≤ 30 ng/mL), before HAART initiation and 6, 12, and 24 months post HAART initiation. In univariate analysis of variance (ANOVA), difference in mean CD4 by vitamin D status is non-significant (F = 0.639, p = 0.424); difference in mean CD4 by time point is significant (ANOVA F = 14.92, p < 0.001), and vitamin D by time interaction is non-significant (F = 0.358, p = 0.783).
24
No. of Patients With EventsParameter RR (95% CI)
Severe complications 1141.5
CVD, liver, or renal deaths
Nonfatal CVD events
31
63
1.4
1.5
Nonfatal hepatic events
Nonfatal renal events
14
7
1.4
2.5
1.0 10.00.1
Risk o
f C
om
plicatio
ns
SMART: Higher CVD incidence with interruption vs. continuous HAART
• CD4-guided drug conservation strategy was associated with significantly greater disease progression or death, compared with continuous viral suppression RR 2.5 (95% CI: 1.8-3.6; P<0.001)
El-Sadr W, et al. CROI 2006. Abstract 106 LB.
Increased risk of myocardial infarction in women with HIV
Large data registry 3,851 HIV-positive patients1,044,589 HIV-negative patients
HIV+
HIV-
Triant et al, J Clin Endocrinol Metab 2007
26
Renal disease in women living with HIV
• Women living with HIV may be at an increased risk for acute renal failure or CKD– risk of HIV-associated nephropathy and/or ART induced
renal dysfunction– renal complications can increase mortality among
women living with HIVP<0.0001
Gardner LI et al (2003) J Acquir Immune Defic Syndr
Co-morbidities
Reduced bone mineral
density
Emotional challenges
Cardiovasculardisease
Renal dysfunction
Cancer
Shiels et al, JAIDS 2009
Meta-analysis of incidence of non-AIDS cancers in people with HIV by gender
Includes 18 studies; SIR = standardised incidence ratio
29
Neurological function in women with HIV
• Neurological impairment present in ≥50% of people living with HIV
• Neurological dysfunction, including memory impairment and psychomotor function, has been shown to be increased in women with HIV
• Risk increases with age
Clifford DB (2008) Top HIV Med
CDC: Centers for Disease Control and Prevention; A = asymptomatic; B = Symptomatic; C = AIDS indicator
conditions
CRANIum study: Women have a higher rate of depression compared with men
• Prevalence of depressive symptoms in women in the study is twice as high as the general population in Europe
Bayon et al, 2nd International Workshop on HIV and Women, Abst 0_1. 2012
15.714.3
17.9
13.3
10.6
20.8
16.816.517.2
p<0.0001
p<0.01
HIV-positive patients aged ≥ 18 years; Depression = HADS-D ≥ 8
All patients (n=2862)Male (n=1766)
Female (n=1096)
CRANIum study: Treatment-naïve women have a higher rate of anxiety compared with
men
p=0.07p=0.02
p=0.51
35.332.8
39.1
33.332.0 32.930.6
33.5 34.3
All patients (n=2862)Male (n=1766)
Female (n=1096)
Bayon et al, 2nd International Workshop on HIV and Women, Abst 0_1. 2012HIV-positive patients aged ≥ 18 years; Anxiety = HADS-A ≥ 8
EVhA: quality of life in women living with HIV in Spain
Cabrero et al. IWHW 2013, abstract 13.
Cross-sectional single-visit
studies
• Sign and date informed consent• Sociodemographics• Clinical data for women living
with HIV• Sexual sphere
Young women living with HIV vs control
cohort (EVhA1)
Mature women living with HIV vs control
cohort (EVhA3)
Inclusion criteria• Aged 16–22 years• HIV• On stable ART ≥ 3 months
Inclusion criteria (controls)*• Aged 16–22 years• No HIV or high-risk
behaviour• Similar education and
employment
Inclusion criteria• Aged 35–60 years• HIV• On stable ART ≥ 3 months
Inclusion criteria (controls)*• Aged 35–60 years• No HIV or high-risk
behaviour• Similar education and
employment
*Protocol suggested possible sources of controls: relatives, friends, hospital employees. †Paired women HIV/no HIV; EVhA: Epidemiology study of women living with HIV
Outcomes†
• Quality of life• Mood stages• Neurocognitive
function
Young vs mature women in Spain: EVhA1 vs EVhA3 sub-analysis (= EVhA2)
EVhA: young women living with HIV less impaired QoL than mature women
Transient health
QoL
Cognitive function
Health problems
Mental health
Energy
Social function
Role functional
Physical function
Pain
Global health
• The MOS-HIV revealed mean scores were lower in mature women living with HIV compared to younger women
• Only one dimension, cognitive function, showed similar values for younger and mature women
• All other dimensions favoured younger women, with significant differences in social function, transitory health and global health
Cabrero et al. IWHW 2013, abstract 13.
EVhA: overall conclusions
• Young women living with HIV show less damage in their sexual sphere, better mood stage and neurocognitive function, and higher QoL scores than their mature counterparts
• For mature women, both anxiety and depression positive screening were related factors with lower QoL risk scores
• Further work is needed to investigate how clinical-demographic differences (e.g. HCV co-infection) between groups affect these findings
• Multidimensional care with a special focus on mental health and mood may be critical to improving the wellbeing of older and aging women living with HIV
Cabrero et al. IWHW 2013, abstract 13.
35
Definition of frailty
• In attempting to define frailty as an independent syndrome (or phenotype), three of the following criteria need to be present:
Unintentional weight loss
Self-reported exhaustion
Low physical activity
Slowness – measured by time taken to walk 3m
Weakness – grip strength
Fugate Woods N et al (2005) J Am Geri Soc
Prevalence of age-related co-morbidities in people living with HIV
• Co-morbidities analysed: hypertension, type 2 diabetes mellitus, cardiovascular disease and osteoporosis
100%
75%
50%
25%
4%
0%≤40 yrs
N=542
41–50 yrs
N=1724
51–60 yrs
N=452
>60 yrs
N=136
80%
60%
42%21%
16%
1%3%
1%8%
0%6%
31%
35%
17%
31%
29%
15%
HIV-positive
¼%2¾%
HIV-negative
No age-related diseases 1 co-morbidity 2 co-morbidities 3 co-morbidities 4 co-morbidities
Guaraldi et al, Clin Infect Diseases 2011
100%
75%
50%
25%
0%≤40 yrs
N=1626
41–50 yrs
N=5172
51–60 yrs
N=1356
>60 yrs
N=408
90% 80%
65%
40%
9%0%1%
0%2%
1%6%
17%28%
42%
15%
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