CROI Monday Feb 14: 5 Key Aging &
Metabolic Oral Presentation Studies
1. Higher heart disease risk (myocardial infarction) for PLWH in 2010-2017 compared to people without HIV. |
2. novel imaging technique provides evidence of unique arterial inflammation in PLWH on ART thought to contribute to heightened heart disease risk for PLWH.
3. Addressing the concern that PLWH have higher risk for type 2 diabetes - PLWH have higher fat tissue fibrosis & inflammation markers/pathways identified to be associated with new diabetes diagnosis in PLWH.
4. Functional impairment examined in global REPRIEVE Trial, found 36% impaired with stepwise worsening based on age & 55-59 & >60 yrs old the worst. African-American, BMI, waist circumference, transgender spectrum, Southeast Asia, ARTs relationships associated with worse outcomes. Moderate & severe functional impairment associated with increased heart disease risk.
5. Antcholinergenics drugs common used for older PLWH increase risk for falls & frailty, suggest consideration for limiting use of these drugs.
6. Cognitive Impairment in PLWH & women with HIV in WIHS, in the UK, links to several studies below.
7. Feminizing hormones therapies & cardiovascular disease risks for transgender women.
With the potential adverse cardiovascular effects of newer antiretroviral therapy (ART), such as integrase inhibitors and weight gain and Tenofovir Alafenamide and elevated lipids, it is critical to continue monitoring trends in myocardial infarction (MI) rates by HIV status.
Subjects included people with HIV (PWH) from two health system cohorts: Massachusetts General Hospital (Partners) and Kaiser Permanente Northern California (KPNC), identified from 2005-2017 with follow-up through 2020.
Among PLWH & people without HIV with similar risk profiles at baseline, we observed no difference in MI risk for baseline years 2005-2009, and a 60% higher risk in PLWH for years 2010-2017. Results appear driven by decrease in MI risk for people without HIV, that was not seen fir PLWH.
"HIV-specific risk factors, such as longer HIV duration & newer ART (e.g. INSTIs), may have prevented PLWH from realizing the same improvements in MI risk for people without HIV. Clinical implications for PLWH include continued surveillance for CVD & primary prevention, including possibly more aggressive interventions."
CROI: Trends in Myocardial Infarction Risk by HIV Status in Two US Healthcare Systems - (02/14/22)
Persistent immune activation and downstream macrophage-specific arterial infiltration are thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with HIV (PWH) on ART. We applied a novel macrophage-specific imaging modality to investigate macrophage-specific infiltration among participants with vs without HIV in relation to atherosclerotic plaque and immune activation..
These data applying a novel imaging modality provide unique evidence of macrophage-specific arterial inflammation among PWH on ART, which relates specifically to non-calcified plaque. Additionally, we characterize key immune pathways relating to increased arterial inflammation of relevance to identifying novel immunomodulatory therapies for CVD reduction.
CROI: Macrophage-specific arterial infiltration relates to plaque type and immune activation in HIV - (02/14/22)
these data may suggest a potential role of this pathway in subcutaneous adipose tissue fibrosis and insulin resistance in treated HIV..
People with HIV (PWH) are at increased risk for type 2 diabetes (T2D), which has been linked to persistent inflammation despite ART. PWH have also been reported to have increased adipose tissue fibrosis, which has also been linked to insulin resistance, but the inflammatory pathways most closely linked to incident T2D and adipose tissue fibrosis in this setting remain unclear. Many inflammatory pathways, including the kynurenine pathway of tryptophan catabolism, predict incident T2D in treated HIV infection. PWH also have abnormally high SAT fibrosis. Higher IL-6, IL-18, IP-10, sCD163, suPAR, sTNFR2 and kynurenine-to-tryptophan (KT ratio) were associated with incident T2D (Figure)....
CROI: PLWH Have Higher levels of Fat Tissue Fibrosis - INFLAMMATION AND KYNURENINE PATHWAY LINKED TO TYPE 2 DIABETES AND FAT FIBROSIS IN HIV - (02/14/22)
Over 1/3 reported functional impairment. Physical function impairments occur earlier in people with HIV.
A global analysis (REPRIEVE Study) of people with HIV infection found 28% of participants had some functional impairment, 8% had moderate impairment, and fewer than 0.5% had severe impairment. Diverse studies found that functional impairment begins at a younger age in people with HIV. But little is known about differences in functional impairment by global region, gender, or antiretroviral therapy (ART) regimen.
The 7736-person analysis found significant differences in self-reported function; for example, the worst function occurred in South Asia (India) and the best in adjacent Southeast/East Asia (Thailand).
- Black race (higher income areas only), older age, identifying as female, and longer ART duration were also identified risks
Functional impairment was associated with cardiometabolic risk. WAIST Circumference was associated with impairment & severe impairment.
- DASI may provide an estimate of cardiometabolic risk; longitudinal associations will be investigated in ongoing REPRIEVE follow-up.
- Other variables significantly associated with physical function: cisgender women and"across the transgender spectrum" independently had worse function than cisgender men; function proved independently worse with each added 5 years of age compared with 40-44 (see graph showing stepwise worsting with age & 60+ the worst !!!) ; obese (BMI) people independently had worse function than overweight or normal-weight people; current and former smokers independently had worse function than never-smokers; people with longer ART duration independently (10+ yrs worse than 5, 5 worse than <5) had worse function than those with fewer than 5 years of ART; people who took a protease inhibitor or an integrase inhibitor regimen independently had worse function than those who took a nonnucleoside regimen; longer thymidine analogue exposure of 10 years or more was associated with functional impairment; and in high-income countries blacks or African Americans independently had worse function than whites.
CROI: Geographical Differences in Fnctional Impairment of PLWH: Over One Third in Global HIV Analysis Have Impaired Physical Function - (02/14/22)
Researchers working with the UK/Ireland POPPY cohort noted that clinicians prescribe anticholinergics to treat mental health conditions, bladder trouble, or allergies-all concerns common to an aging HIV population. Side effects can include dry mouth, urinary retention, and constipation. This POPPY study set out to see if taking anticholinergics affects frequency of two age-related problems-falls and frailty.
Analysis of 699 older people with HIV linked use of two or more anticholinergic drugs to 3.6-fold to 4.5-fold higher odds of recurrent falls and to doubled odds of frailty . Findings reflect similar prior results in the general population.
After statistical adjustment for demographic, lifestyle, and clinical factors, any anticholinergic almost doubled odds of recurrent falls in an association that stopped short of statistical significance (odds ratio [OR] 1.9, 95% confidence interval [CI] 0.9 to 4.0, P = 0.08). The same analysis tied any anticholinergic use (nonsignificantly) to 70% higher odds of frailty (OR 1.7, 95% CI 0.9 to 3.0, P = 0.08).
the researchers stressed that their findings echo studies of anticholinergic associations in general populations worldwide, so they suggested clinicians consider these potential anticholinergic impacts and lower use of these drugs when possible.
CROI: Two or More Anticholinergics Tied to Falls, Frailty in People With HIV - (02/14/22)
CROI: PREVALENCE OF ANEMIA AND RISK FACTORS IN PEOPLE WITH HIV IN THE MODERN ART ERA - (02/14/22)
CROI: Assessing health-related quality of life in people with HIV and cognitive issues - (02/13/22)
CROI: COGNITIVE PREDICTORS OF EVERYDAY FUNCTIONING IN THE WOMEN'S INTERAGENCY HIV STUDY - (02/12/22)
CROI: Abnormal cognitive aging is detected despite clinically defined cognitive stability - (02/12/22)
CROI: Decreased Myelin Content and Cognitive Performance in Adults with Perinatal HIV - (02/13/22)
CROI: PETRAM RESULTS: BONE TURNOVER CHANGES ON 18F-NaF PET/CT AFTER A RANDOMISED SWITCH TO TAF - (02/13/22)
CROI: IMPACT OF INTEGRASE STRAND TRANSFER INHIBITORS ON COGNITION IN THE HAILO COHORT - (02/12/22)
CROI: FEMINIZING HORMONAL THERAPIES WORSEN CARDIOMETABOLIC PROFILES IN TRANSGENDER WOMEN - (02/12/22)
NATAP reports, coverage:
Conference on Retroviruses
and Opportunistic Infections
February 12-16, 2022