Fat & HIV was a big part of CROI 2020
................elevating this issue to a higher level than before seen at CROI, and raising the stakes for PLWH who are aging & the impact of fat & fat metabolism on HIV+ for mortality, frailty, physical function, cognitive & brain function. Its a correlation that in my opinion is very key resulting from immune system & fat metabolism disturbance & dysregulation critical to why PLWH are aging more quickly & with greater comorbidities & dying sooner, 9 years sooner on average than HIV- except if ART was started at >500 CD4 they reported no worse mortality, reported in the Kaiser mortality study at CROI by Julia Marcus: http://natap.org/2020/CROI/croi_134.htm |
Themed Discussion FAT IN FOCUS - (03/11/20)
PWH had a greater burden (5x) of primarily eccentric arterial wall enhancement compared with persons without HIV (03/27/20)...100% with undetectable viral load, average age 56-59, 85% white, median CD4 492, the number of CVD risk factors was equal between HIV+ & HIV- except HIV+ used statins MORE & used marijuana MORE.
MITOCHONDRIAL DNA, COGNITIVE FUNCTION, AND FRAILTY IN OLDER ADULTS WITH HIV (03/17/20)
In this study we show a relationship between elevated levels of plasma mtDNA and lower performance on the MoCA, greater exhaustion, and slower walk, suggesting mtDNA may have a role as a novel biomarker in assessing pathogenic inflammation associated with cognitive dysfunction and some components of frailty in PLWH.
5 studies highlighted in this oral session at CROI in "Fat in Focus"
Below are links to these 5 studies:
1. FAT GAINS OCCUR AFTER ART WITHOUT CHANGES IN METABOLIC RATE OR CALORIC INTAKE
Allison Ross Eckard
2. GREATER WEIGHT GAIN AFTER SWITCH TO InSTI-BASED
REGIMEN FROM NNRTI VS PI REGIMENS...of note those switching from PI had early small weight gain then it declined while for those switching from NNRTI they had increasing weight gain
3. BODY COMPOSITION CHANGES OVER THE MENOPAUSAL TRANSITION IN HIV+ AND HIV-WOMEN....increased waist circumference and a little also but not as much BMI compared to HIV-
4. RESISTIN GENE POLYMORPHISM RELATED TO WEIGHT GAIN AND PSYCHIATRIC SYMPTOMS ON InSTI
5. ADIPOCYTE DYSFUNCTION DESPITE REDUCED ADIPOSE INFLAMMATION IN DIABETICS WITH HIV
......then there was a talk by Jordan Lake discussing fat & HIV and how and why fat is contributing to the comorbidities & aging problem HIV+ are experiencing; the legacy affects of belly fat increases & lipoatrophy & fat wasting that contributes to metabolic complications & increased comorbidities among older HIV+; how these problems + weight gain & increased fatty muscle contribute to sarcopenia & other complications:
METABOLIC COMPLICATIONS OF HIV AND ITS THERAPIES
Themed Discussion FAT IN FOCUS - (03/11/20)
Adipocyte Dysfunction Despite Reduced Adipose Inflammation in Diabetics with HIV (04/01/20).....In one of the largest and broadest assessments of adipose tissue gene expression in non-diabetic vs. diabetic PWH on modern ART, we found pronounced differences in adipocyte-related genes, consistent with dysregulation of metabolic pathways in diabetes.
FAT GAINS OCCUR AFTER ART WITHOUT CHANGES IN METABOLIC RATE OR CALORIC INTAKE - (05/06/20) Resting energy expenditure (aka resting metabolic rate (RMR)) is a highly accurate, non-invasive metabolic assessment to evaluate a person's daily calorie (i.e.energy) requirements in order to maintain basic body functions while in a state of rest. To date, however, resting energy expenditure (commonly referred to as resting metabolicrate (RMR)) has not been investigated in PWH before and after ART initiation. This study does not support the hypothesis that changes in caloric intake or metabolic rate are responsible for increases in weight and fat accumulation after ART initiation. Pre-treatment metabolic rate, however, independent of HIV-RNA, may play a significant role in subsequent weight gain and fat accumulation after ART initiation. Notably, weight gain and fat accumulation were still significant after adjusting for sex, baseline RMR, HIV-RNA,and CD4 cell counts, suggesting that there are additional unidentified factors contributing to the pathogenesis. Continued enrollment, extended followup, and additional investigations are on-going to further explore possible etiologies of this phenomenon
GREATER WEIGHT GAIN AFTER SWITCH TO INSTI-BASED REGIMEN FROM NNRTI VS. PI REGIMENS - (03/11/20)
PWH on stable NNRTI-based ART with long-term viral suppression had higher annualized weight gain after a switch to INSTI regimens compared to person who switched from PI-based ART. Among those switched from NNRTI-to INSTI-based ART, annualized weight gain was greatest for females, non-whites and older PWH. These findings may reflect a heterogenous effect of ART class and agent on body weight regulation that is not limited to the initiation of first regimens in the treatment-naïve. Of note those on PI before switch had a similar increase in weight as those on NNRTI but weight decreased for those then who were n PI but continued increasing for those on NNRTI.
Body Composition Changes Over The Menopausal Transition In Women With and At Risk For HIV
HIV+ had increased waist circumference by about 12% as seen just below in figure 2, and BMI increased too but by about 3% compared to around 8% for HIV-, authors say HIV blunts BMI increase, I think there are additional factors at play. Pdf attached above
CROI: Body Composition Changes Over The Menopausal Transition In Women With and At Risk For HIV - (05/11/20)
RESISTIN GENE POLYMORPHISM RELATED TO WEIGHT GAIN AND PSYCHIATRIC SYMPTOMS ON InSTI - (05/07/20)
ADIPOCYTE DYSFUNCTION DESPITE REDUCED ADIPOSE
INFLAMMATION IN DIABETICS WITH HIV Adipocyte Dysfunction Despite Reduced Adipose Inflammation in Diabetics with HIV (04/01/20)
Samuel Bailin, Spyros Kalams, Simon Mallal, Fei Ye, Run Fan, Mona Mashayekhi, Curtis Gabriel, John Koethe, Celestine Wanjalla
METABOLIC COMPLICATIONS OF HIV AND ITS THERAPIES (03/17/20) [AT=adipose (fat) tissue]
FAT GAINS OCCUR AFTER ART WITHOUT CHANGES IN METABOLIC RATE OR CALORIC INTAKE - (05/06/20)
INCREASED INFLAMMATORY CX3CR1+GPR56+CD57+ CD4+ T CELLS IN FAT FROM HIV+ DIABETICS - (05/06/20)
[ HIV+ are at risk for developing diabetes at they age with rates of diabetes in older HIV+ higher than in younger HIV+ & HIV-negs. HIV+ with diabetes appear to have disrupted fat tissue metabolism. Diabetes is associated with mortality & decreased quality of life, as it progresses it can be difficult to manage. There appears to be a difference in the affect of diabetes in HIV+ vs HIV- that may results in worse metabolic overall outcomes. Jules]
CYP2B6 GENOTYPE AND WEIGHT-GAIN DIFFERENCES BETWEEN DOLUTEGRAVIR AND EFAVIRENZ - (05/06/20)
Postpartum weight changes in women initiating DTG vs EFV in pregnancy: DolPHIN-2 - (04/27/20)
NAFLD AND LIVER FIBROSIS PREDICT HIGH CARDIOVASCULAR RISK IN HIV-MONOINFECTED PATIENT (04/02/20)
Fibrosis Progression Over 6-Fold Higher in NAFLD With vs Without HIV - (03/23/20)
VISCERAL FAT IS A PREDICTOR OF LIVER FIBROSIS AND FIBROSIS PROGRESSION IN PEOPLE LIVING WITH HIV (03/23/20)
EFFECTS OF HIV, AGE, AND SEX ON SKELETAL MUSCLE MASS AND DENSITY (04/01/20)
"Older age and being a woman was associated with smaller and fattier muscle, while obesity was associated with larger and fattier muscle. Detrimental effects of HIV on the psoas density and area, particularly among men, may have important implications on balance, trunk stability, and mobility."
The psoas muscle is located in the lower lumbar region of the spine and extends through the pelvis to the femur. This muscle works by flexing the hip joint and lifting the upper leg towards the body. A common example of the movement created from this muscle is walking
Baseline and Acquired Comorbidities in Patients Initiating ART in the HOPS, 2008-2018 (04/07/20)
Comorbidities at CROI - mortality, aging..... - (04/20/20)
Low Bone Mineral Density in Older People Living with HIV: the Renal-Bone Axis and ART - (04/20/20)
Much Higher Death Rate After Cancer Diagnosis in People With HIV - (03/20/20)
MK-8591/Islatravir vs ART Resistance / Metabolics (04/09/20)