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Improving HIV chronic care and health outcomes Antonella dArminio - - PowerPoint PPT Presentation
Improving HIV chronic care and health outcomes Antonella dArminio - - PowerPoint PPT Presentation
Improving HIV chronic care and health outcomes Antonella dArminio Monforte Institute of Infectious and Tropical Diseases, Department of Health Sciences University of Milano % suppressed among those on ART: Prevalence of different non-AIDS
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Prevalence of different non-AIDS related co-morbidities at different age strata in naive patients
Jan 2017 Report
0.4% 0.8% 0.8% 0.3% 1.4% 2.9% 0.5% 1.6% 3.7% 0.2% 0.8% 0.1% 0.2% 1.6% 2.9% 14.8% 0.5% 0.7% 2.1% 0.5% 1.2% 0.8% 0% 2% 4% 6% 8% 10% 12% 14% 16% <=50 n=12569 51-60 n=1780 >60 n=486 naive Cerebrovascular Diabetes Hypertension Myocardial infarction Lipodystrophy eGFR <60 Non-AIDS defining malignancies ESLD
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Prevalence of different non-AIDS related co-morbidities at different age strata in ART - treated patients
Jan 2017 Report
0.7% 1.1% 3.4% 1.1% 1.9% 4.3% 1.6% 3.1% 5.7% 0.5% 0.7% 1.7% 3.9% 2.4% 3.1% 6.1% 9.8% 26.7% 1.4% 2.4% 5.2% 1.0% 0.9% 1.2% 0% 5% 10% 15% 20% 25% 30% <=50 n=10787 51-60 n=2997 >60 n=997 experienced Cerebrovascular Diabetes Hypertension Myocardial infarction Lipodystrophy eGFR <60 Non-AIDS defining malignancies ESLD
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0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Total (n=3909) 1999–2000 (n=256) 2001–2002 (n=788) 2003–2004 (n=862) 2005–2006 (n=718) 2007–2008 (n=658) 2009–2011 (n=627)
Unknown Other Non-AIDS cancer CVD-related Liver-related AIDS-related
Most common causes of death in HIV-positive individuals
All deaths
D:A:D - CAUSES OF DEATH IN HIV-POSITIVE INDIVIDUALS
Non-AIDS cancer is the leading non-AIDS cause of mortality and there is no evidence of improvement
Smith CJ et al. Lancet 2014;384:241–248 Year
Prospective cohort of 49,731 HIV-positive individuals from the D:A:D study at 212 clinics in Europe, the USA and Australia, 1999–2011
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1991 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 1992
Increase in non-AIDS-defining malignancies (NADM)
Adapted from Shiels MS et al. J Natl Cancer Inst. 2011;103:753-62
AIDS-defining malignancy NADM
Incidence rate per 100,000 person-years Incidence rate per 100,000 person-years 8000 7000 6000 5000 4000 3000 2000 1000 7000 6000 5000 4000 3000 2000 1000 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2500 2250 2000 1750 1500 1250 1000 750 500 250 800 700 600 500 400 300 200 100 0–12 years 20–29 years 40–49 years 60 years and older 13–19 years 30–39 years 50–59 years Number of NADM Number of AIDS-defining malignancies
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In a clinical prospective study, 98,687 HIV-positive and demographically matched HIV-negative veterans in the USA contributed 583,178 PYFU, 2003–2010
VACS
PREVALENCE OF END-STAGE RENAL DISEASE (ESRD)
HIV-positive adults have a higher risk of ESRD age-associated events, but they occur at similar ages than those without HIV
Althoff KN et al. Clin Infect Dis 2015;60:627–638
Overall and age-specific IRs (and 95% CIs) for ESRD
Incidence rate per 1,000 PY 9.00 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00 <40 40–49 50–59 60–69 ≥70 Age group (years) HIV-negative HIV-positive
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PATHOPHYSIOLOGY OF CVD IN HIV-POSITIVE INDIVIDUALS
Hemkens LG and Bucher HC. Eur Heart J 2014;35:1373–1381 Dyslipidemia, lipodystrophy, insulin resistance Adipose tissue and liver dysfunction Immune activation Viral replication Lymphocytes T cell activation (CD38+) Vascular and endothelial dysfunction Hypertension, atherosclerosis, myocardial infarction Coagulation disorders Chronic inflammation Adipocytes ART HIV
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NA-ACCORD
SMOKING, HTN, AND ALCOHOL CONTRIBUTE TO MI RISK IN HIV
- Retrospective meta-analysis of pts with
validated MI events from 7 clinical cohorts within NA-ACCORD from 1/2000 to 12/2013 (N = 29,515)[1]
– Population attributable fraction: proportion of MIs avoidable by prevention of modifiable HIV-related and traditional MI risk factors – 347 pts (1.2%) had type 1 MI due to plaque rupture – Sensitivity analysis added for 16,687 pts (57%) with BMI data, 227 had type 1 MI
- ~ 40% MI reduction achievable through
prevention of smoking, elevated TC, or HTN, regardless of BMI
- 1. Althoff KN, et al. CROI 2017. Abstract 130. 2. Shepherd L, et
- al. CROI 2017. Abstract 131.
- In separate study (D:A:D), smoking cessation reduced overall cancer
rate after 1 yr, except lung cancer (rate high even after > 5 yrs)[2]
*Adjusted for age, sex, race, and all listed risk factors. †P < .05
Adjusted Population Attributable Fractions for MI,*[1] % MI BMI Subgroup Traditional MI risk factors § Smoking 38† 36 § Elevated TC 43† 39† § HTN 41† 39† § All 3 (smoking, TC, HTN) 86 HIV-related MI risk factors § DM 2 4 § CKD 3 3 § CD4+ cell count 10† 14† § VL 6 8 § AIDS 2
- 1
§ HCV coinfection 8† 14†
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Adjusted relative rate/year of PI: 1.15 (1.06, 1.25) Adjusted relative rate/year of NNRTI: 0.94 (0.74, 1.19) Number of MIs per 1000 PYFU (IC 95%) Years of exposure to PI or NNRTI 2 4 6 8 10 >6 5–6 2–3 3–4 4–5 1–2 <1
Friis-Møller N et al. N Engl J Med 2007;356:1723-35
D:A:D study
Higher risk of MI with PI exposure (but not with NNRTI exposure)
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RISK FACTORS IN DEVELOPING HIV NEUROCOGNITIVE DISORDERS
- 1. Cross S et al. J Neuroimmune Pharmacol 2013;8:1114–1122; 2. Attonito JM et al.
Front Public Health 2014;11:105; 3. Ellis R and Letendre SL. Neurotherapeutics. 2016;13(3):471–476; 4. Anand P et al. AIDS Behav 2010;14(6):1213–1226
CD4 nadir1 Duration of HIV infection2 CNS toxicity of ART4 CNS penetration
- f ART3
CNS OI3 HCV1,4 HIV CSF escape3 Mental health1,4 NCD4 Other dementias4 Alcohol & recreational drugs2,4 Race1 Education1
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- In the context of long-term ART (2 or more years after starting initial treatment), older age was a significant
risk factor for neurocognitive impairment.
- Age-related neurocognitive impairment was seen despite continued virologic suppression in most and despite
neurocognitive improvement (lower impairment rate at later follow-up visits) in the cohort as a whole.
- Potential causes of age-related neurocognitive impairment: a) ART-related adverse effects of common age-
related comorbidities (diabetes, hypertension, hyperlipidemia); b) greater CNS toxicities of ART in older versus younger participants. The AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study was a prospective cohort of HIV+ ART-naive individuals (n=3313) enrolled in 7 randomized ART parent trials.
ALLRT
IMPACT OF ADVANCING AGE ON COGNITION IN HIV+
Coban H, et al. CROI 2017, Seattle (WA). Abst.#343
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Odds of osteoporosis in HIV-infected patients compared with HIV-uninfected controls
Brown and Qaqish. AIDS 2006;20:2165-74
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FACTORS ASSOCIATED WITH RISK OF ABNORMAL BMD OF SPINE AND HIP IN HIV+ INDIVIDUALS
- 1. Das S et al. Recent Pat Antiinfect Drug Discov 2014;9:6–13;
- 2. McComsey GA et al. Clin Infect Dis 2010;51(8):937–946
Race Older age (>40 years) Low vitamin D Female gender Low BMI
Elevated parathyroid hormone levels
ART Tobacco, alcohol and
- piate abuse
CD4 cell count
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Novel CVD Risk Factors in HIV: Inflammation and Immune Activation
- SMART study showed increased
CVD event rates in drug conservation (episodic treatment)
- vs. viral suppression (continuous
treatment) group
- HR=1.57, P=0.05
- Primary endpoint recurrent
OI/death
- Inflammatory markers IL-6 and
d-dimer increased 1 month after treatment interruption in SMART
- Baseline hsCRP, IL-6, and d-
dimer strongly correlated to
- verall mortality
El-Sadr NEJM 2006; Phillips AIDS 2008; Kuller PLoS 2008.
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Improving HIV chronic care and health
- utcomes: conclusions