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Aging/Comorbities at IAS
  Jules Levin, NATAP
There are several particularly noteworthy/interesting studies at IAS. First the 2 TAF studies immediately below report benefits in kidney & bone safety after switching to TAF. The 2nd noteworthy study found that bone loss persists after the first 2 years after starting ART & bone loss persists for 7 years, as long out as study goes, and this is contrary to what all other studies have recently reported, they reported that initial bone loss stops after starting ART about 2 years out, I knew this made no sense & definitely did not believe that, there is no way bone loss stops 2 years after ART is initiated for everyone, made no sense. Next, an interesting study on "Eliciting Cognitive Difficulties...." reports qualitative reporting of cognitive difficulties HIV+ are experiencing & I think importantly puts a better "real--life" understanding to what patients experience, living with HIV is not as easy as many think & these cognitive difficulties reported by patients reflect some of the real-life difficulties! The study below on telomere length reports how early after HIV infection telomere shortens and this reinforces what authors conclude but many studies previously reported that - cellular aging (immunosenescense) occur soon after HIV infection! Below is a study from the VA indicating the poor bone care patients received in VA, study ended in 2010 - patients in this study were not receiving DEXA scan, only 7.3% recd DXA scan, only 16% had Vit D levels measured, pretty astonishing at this point. There are 2 studies below finding subclinical cardiac strain in HIV+ in the USA & 2nd study in Africa highlighting that the aging issue is global, these studies find a high prevalence of subclinical cardiac strain that are associated with inflammation & immune activation & these findings are "independent of CD4 & undetectable viral load" reinforcing what has been a loud major discussion in recent years at CROI that heart disease & of note subclinical heart disease hangs over as a major concern for HIV+ and particularly for aging/older HIV+ and even with normal CD4 & undetectable viral load the specter of heart disease is a difficult one because these data suggest just taking all the regular precautions like lowering lipids, healthy diet & exercise may not be enough to normalize the risk HIV+ face compared to HIV-negatives; of course a healthy diet & exercise will help but it may not be enough to normalize the risk HIV+ face vs HIV-negatives. One study below found current substance abusers had higher risk for comorbidities, we know many HIV+ are current substance abusers, this study also found higher inflammation markers are associated with increased risk for comorbidities. Nonetheless HIV itself even with normal CD4 & undetectable viral load increases risk for comorbidities, HIV damages the immune system & low nadir CD4 increases risk. an interesting question is - for newer/younger patients who started ART at higher CD4s at 500 or so - will their risk for comorbidities, for accelerated aging be the same as the older generation who started ART with low CD4 nadir? Starting ART earlier certainly will decrease risk but clearly HIV damages the immune system upon infections, studies show immediate ART during acute infection lessens the damage but does not eliminate it - the damage is done, is not preventable but ART when CD4 is higher is helpful. There is a study below reporting HIV+ with asymptomatic neuro impairment are more likely to go on to symptomatic impairment suggesting that many HIV+ may not realize they have neurologic or cognitive impairment but they may have it, and I think this reflects a real-life scenario, that many HIV+ who are younger 25-50 yrs old may not realize they do have some cognitive impairment, but as the study finds these patients were more likely to develop symptomatic neurologic impairment; this is one of several major concerns aging HIV+ face - cognitive/neurologic impairment, heart disease, mobility problems that reflect gait impairments & frailty onset & this will result in more falls & fractures - all the literature in the general literature reports older people who fall & experience a fracture - it is very difficult to recover, mortality rates increase for these patients who are older & fall - after any person reaches about 64 yrs old the immune system changes, it degrades, and recovery from hard "hits" like this is very difficult. Not to mention depression & suicide. In my discussions with clinicians who have large HIV practices over 50% of older HIV+ are on anti-depressants, many younger patients take ADHD drugs & other drugs for sleeping, making it very difficult to understand the future for patients regarding cognitive impairment as they progress to older age. No matter how you cut it in general HIV+ individuals as it is generally accepted experience about 10 years accelerated aging vs HIV-negatives reflecting why AGING & HIV needs a lot of attention, much more than it gets, issues include loss of income, housing, depression, mobility, suicide.
These 2 studies report benefits found in renal & bone safety for TAF use vs tenofovir, the 1st study below is the first switch study of patients on TDF to TAF & the 2nd study below reviews benefits for patients switching who have renal impairment:
IAS: Switching From a Tenofovir Disoproxil Fumarate (TDF)-Based Regimen to a Tenofovir Alafenamide (TAF)-Based Regimen: Data in Virologically Suppressed Adults Through 48 Weeks of Treatment - (07/22/15)
IAS: Subjects with Renal Impairment Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Have Improved Renal and Bone Safety through 48 Weeks Study GS-US-292-0112 - (07/22/15)
This study is of note because contrary to belief & other studies reporting bone loss occurs after ART initiation & loss plateaus after 48 weeks, NO this study finds bone loss persists after as long as was followed in this study - 7 years:
IAS: (ACTG) Long-term Bone Mineral Density Changes in Antiretroviral-treated HIV-Infected Individuals, Bone Loss Continues--Though Slowly--After First 96 Weeks of ART - (07/22/15)
Interesting report on the types of cognitive difficulties HIV+ report:
Developing serious comorbidities.serious non-AIDS events found associated in this study with elevated inflammation markers & current substance abusers also have increased risk - events include: cancers, heart disease, kidney and liver-
IAS: Serious Non-AIDS Events and Biomarker Changes in HIV-1-Infected Individuals - Inflammation Markers & Comorbidities: higher markers in HIV+ with comorbidities - (07/31/15)
This study reviews hospitalization rates in Italy for non-AIDS comorbidities like cancers & heart disease & liver disease and finds increases for non-AIDS cancers, although heart disease hospitalizations remains unchanged rates still concerning, the same for liver disease
IAS: Aging, Hospitalization Rates for Liver/GI - Rates Increased for Cardiovascular Disease & Non-AIDS Cancers in Italy - Mark Mascolini - (07/29/15)
Of note, this study reinforces that HIV shortly after infection disrupts immunity such that immunosenescence emerges & thereby is accelerated in HIV
IAS: TELOMERE LENGTH SHORTENING AND DNA METHYLATION DISRUPTIONS OCCUR EARLY FOLLOWING HIV SEROCONVERSION.... ......"This suggests that cellular aging and methylomic disruptions are likely to occur soon after contraction of HIV." - (07/31/15)
This disturbing study reports although study followed people until only 2010 that bone care stinks among HIV+ providers-
IAS: Evaluation and Management of Fracture Risk in HIV Patients in the VA system: .....Fractures - HIV+ Vets NO SCREENING/PREVENTION! ..... One Quarter of HIV+ Vets Have Recurrent Fracture--After Minimal Testing or Treatment - Mark Mascolini - (07/31/15)
IAS: Predicting Fractures by DEXA- new technique - (08/10/15)
IAS: Poor Bone Prevention/Care in VA - (07/31/15)
IAS: Bone Mineral Density and Fat Distribution in Adults Randomized to Maraviroc (MVC) Once Daily With Darunavir/Ritonavir (DRV/r) vs. Tenofovir/Emtricitabine (TDF/FTC) With DRV/r: Week 48 Results From MODERN - (07/24/15)
IAS: Myocardial Strain Abnormalities Detected by Speckle-Tracking Echocardiography in Persons with HIV - (08/03/15)
Chronic Hepatitis C Virus Infection Is Associated with Subclinical Coronary Atherosclerosis in the Multicenter AIDS Cohort Study (MACS): a Cross-Sectional Study - (08/13/15)
IAS: Heart Disease/Subclinical Heart Disease/Immune Activation/Inflammation....exercise, diet......."Squelching chronic inflammation with diet and exercise is in many ways a no-brainer" - (08/03/15)
Aging/Comorbidities/Immunity/Early Aging Senescence....HCV liver disease - (07/30/15)
IAS: HIV infection and vascular stiffness among older-adults taking antiretroviral therapy in rural Uganda.... arterial stiffness occurs more often in HIV+ .....aging/HIV in Africa - (08/06/15)
IAS: Asymptomatic neurocognitive impairment (ANI) is associated with progression to symptomatic HIV-associated neurocognitive disorders (HAND) in people with HIV: results from The Ontario HIV Treatment Network (OHTN) cohort study..... - (08/06/15)
IAS: Mortality Steady and Non-AIDS Deaths Rising in British Columbia Since 2005 - Mark Mascolini - (07/29/15)
IAS: Incidence of Syphilis, Other STIs Rising Steadily in HIV+ MSM of France - Mark Mascolini - (07/24/15)
IAS: STIs incidence in MSM followed since HIV-1 primary infection in the French ANRS-PRIMO cohort..... Does Undetectable Viral Load Influence Sex Behavior - (07/24/15)
Diabetes risk high in men on HAART - (07/17/15)
HIV in the Older Adult, Aging/Comorbidities & Death in HIV....... "Will You Still Treat Me When I'm 64? Care of the Older Adult With HIV Infection" - (07/17/15)
"Grip strength is a strong predictor of cardiovascular mortality and a moderately strong predictor of incident cardiovascular disease" new study finds - (07/17/15)

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