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HIV & Heart Disease, Cognitive/Neurologic Disease, Bone Disease
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Download the PDF here
from Jules: at CROI 2017 D:A:D reported darunavir was associated with CVD but shortly after in April 2 posters reported an analysis finding differently, see the 1st 3 reports just below. At CROI the 4th study below, as has been found in previous studies, found higher billirubin levels decreased or prevented CVD, but did not find an association with Reyataz/r, although Reyataz increases billirubin & previous studies suggest protective CVD affect, but authors said they had limited power to assess ATV & CVD. OF NOTE, 2 weeks ago Novartis announced the interim results of the 1st anti-inflammatory CVD drug, press release below; this very same drug was studied in a HIV+ group in a pilot study presented at CROI by Priscilla Hsue finding positive results, we can expect a follow-uo larger study, hopefully Novartis will provide drug for the study. There were a bunch, about 20, of studies on neurologic & cognitive impairment in HIV at CROI. Although there was some disagreeing findings on the question if neurologic function accelerates or gets worse over time in HIV+ with 1-2 studies finding it did not and other studies finding it did get worse, I do think to me there is little doubt that cognitive impairment gets worse over time in HIV+. The reason the 1-2 studies did not find that is because the 1 study from the UK had a very short followup time of 2 years and that may be too short to really conclude much. Cognitive & neurologic decline may not be linear in that it necessarily declines similarly every year, and there are many factors affecting decline which may vary over time. There is no doubt to me that many older aging HIV+ experience worsening cognitive & neurologic decline after certain approximate ages - maybe 60-65, and course this varies by individual, and certain circumstances including nadir CD4, if they have concurrent comorbidities. Does HIV contribute to worsening cognitive & neurologic decline? Yes, I say. After 65 cognitive function in HIV+ declines, more than for HIV-negatives. There was a study on exercise at CROI, 6th down below. There is no doubt to me that the best preventative to immune decline and cognitive decline is exercise & very clean good diet. Bone loss and fractures are a very serious problem. With aging in older HIV+ the risk for osteoporosis is 400% greater vs HIV-negatives, the seriously increases risk for fracture, and fractures in older people lead to premature death. And falls in older HIV+ occurs more often than in HIV-egatives & the risk for falls is associated with cognitive & neurologic decline. These are serious concerns after both longevity/lifespan & often overlooked quality of life too. The study below found pre-treating with Zoledronic Acid prevents bone loss. The economic health costs associated with aging is 5 fold greater in HIV+ compared to younger HIV+. Many are not aware of this or decide to ignore the impact this will have. Frailty & disability is increasing among older aging HIV+ which will also require that many will need special care & services & many will require being put in old age homes permanently, this is a problem we are not prepared to deal with, we have even had a real discussion about this. You cannot put HIV+ individuals wholesale into HIV-nagetive facilities like that, it will not work. Lastly below is a study on HIV & CVD raising all sorts of questions about what causes CVD in HIV+ - this study found HIV did not, they found an association with ART use over 3 years that disappeared when cocaine use was considered. Traditional risk factors I am sure play a role but what else? It remains unclear. What about inflammation? Probably but that is where exercise & diet come in. IN HIV-negatives exercise & diet reduce inflammation, so a study in HIV is starting toevauate if exercise & diet do the same in HIV+, based on my personal experience its the same in HIV. My inflammation markers were very low after & along with many years of exercise & clean good diet. After suffering a hairline knee patella fracture which healed\ed in 3 months in a soft cast my inflammation markers went up quite a bit. After resuming regular exercising & good clean diet my inflammation markers returned to the same levels before the fracture.
CROI: Association between Cardiovascular Disease & Contemporarily Used Protease Inhibitors - D:A:D (02/22/17)
Evaluation of Cardiovascular Disease (CVD) Risk in HIV-1-infected Patients Treated With Darunavir/Ritonavir (DRV/r) - (04/26/17)
Demographic and Clinical Characteristics of Patients Living With HIV Treated With Darunavir- and Atazanavir-based Regimens in the Real-world Setting - (04/24/17)
CROI: Hyperbilirubinemia prevents cardiovascular disease for HIV+ and HIV-individuals - (02/20/17)
1st CVD Anti-Inflammatory Canakinumab with Positive Phase 3 Results Announced - Studied in HIV at CROI - (06/26/17)
CROI: EXERCISE, OXIDATIVE STRESS AND FIBRINOLYTIC FUNCTION IN HIV-1 INFECTED ADULTS - - (04/17/17)
CROI: CROI: Neurocognitive Disorders - Neurologic, Brain, Cognitive Impairment - - (04/10/17)
CROI: Antiretroviral-induced Bone Loss is Durably Suppressed by A Single Dose of Zoledronic Acid - - (04/05/17)
CROI: Cost of noninfectious comorbidities in patients with HIV - Cost of HIV CARE Increases 5 fold Due to Cost for Comorbidities from <40 to >60 - (03/23/17)
CROI: Darunavir/r Use and Incident Chronic Kidney Disease in HIV-positive Persons - study found increased CKD risk with ATV but not with Darunavir - D:A:D Cohort - (02/20/17)
CROI: Oral Session Thursday: INFLAMMATION AND AGE-RELATED COMPLICATIONS - 4 studies (1) Association between Cardiovascular Disease & Contemporarily Used Protease Inhibitors (2) Smoking Cessation & Impact on Cancers & Lung Cancer Risks in HIV+ (3) New CVD Anti-Inflammatory in Pilot Study in HIV+ (4) Hyperbillirubinemia Prevents CVD Risk - (02/20/17)
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HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms
Jnl of the Am Heart Ass March 2016 - Hong Lai, PhD; Richard Moore, MD; David D. Celentano, ScD; Gary Gerstenblith, MD; Glenn Treisman, MD; Jeanne C. Keruly, MS;
Thomas Kickler, MD; Ji Li, MD; Shaoguang Chen, MS; Shenghan Lai, MD; Elliot K. Fishman, MD
Pdf attached above
"The effect of cocaine use on subclinical atherosclerosis might be stronger than traditional cardiovascular risk.....our results..... did not find evidence for an independent association between HIV infection and subclinical coronary atherosclerosis.....Our study shows that traditional cardiovascular risk profile was significantly associated with the presence of subclinical atherosclerosis. This finding is consistent with other published data.....long-term exposure to ART may increase the risk for subclinical coronary atherosclerosis [from Jules: in this study participants were 59% on PIs, 34% on NNRTIs, no integrase use. This study was conducted between Between June 2004 and February 2015 so subjects had a history of old PIs use. At CROI 2017 D:A:D reported Reyataz/r was NOT associated with CVD http://www.natap.org/2017/CROI/croi_68.htm. Although DAD found DRV associated with increased risk a poster presented subsequently at ACTHIV Conference in april 2017 reported that a pooled analysis of 19 Janssen studies did not indicate increased CVD risk over 6 years use http://www.natap.org/2017/HIV/042617_01.htm - we have yet to have long term CVD risk studies in integrase use]....in our current study, with a sample size over 5 times larger than that in our earlier study, we have found that the associations between HIV infection and subclinical coronary atherosclerosis may be attributed to a markedly worse cardiovascular risk profile in the HIV infected compared to the HIV uninfected....The results in Table 6 show that long-term use of ART may not impose significant risk of subclinical coronary atherosclerosis in those who never used cocaine, whereas the adverse effect of long-term ART use on subclinical coronary atherosclerosis is very apparent in chronic cocaine users.
.......It is critically important to emphasize that despite the fact that an overall nonsignificant association between HIV infection and subclinical coronary atherosclerosis was observed, the findings of this study should not be interpreted as evidence against existence of the adverse cardiovascular consequences of HIV infection"
CONCLUSIONS: "These limitations notwithstanding, our findings may have important implications for the prevention of HIV/ART-associated CAD, especially in AAs. This study revealed a high prevalence of subclinical coronary atherosclerosis in AAs without cardiovascular symptoms, that CAD risk profiles are more adverse in AAs with HIV infection than in HIV uninfected, that long-term exposure to ART may increase the risk for subclinical coronary atherosclerosis, especially in chronic cocaine users, and that HIV infection per se may have no appreciable impact on subclinical coronary atherosclerosis in this population. Although our findings should be regarded as tentative and replication in other cohorts is needed, they suggest that it will be particularly important to prevent and retard coronary atherosclerosis, to aggressively manage traditional risk factors for coronary atherosclerosis in HIV-infected patients who will be receiving potentially long durations of ART, and that abstinence from cocaine or reduced cocaine use in HIV-infected individuals must be one of the highest priorities for preventing HIV/ART-associated coronary atherosclerosis."
"Prevalence of subclinical coronary atherosclerosis reported in this study was different from other published data....Unlike our results, which did not find evidence for an independent association between HIV infection and subclinical coronary atherosclerosis, Post et al. found a significant association between HIV infection and coronary plaque (adjusted PR for age, race, CT scanning center, and cohort) was 1.14 (95% CI, 1.05, 1.24; P=0.001).....The effect of cocaine use on subclinical atherosclerosis might be stronger than traditional cardiovascular risk. ......Our study also demonstrated that the adverse effects of long-term ART use may be modified by cocaine use. The results in Table 6 show that long-term use of ART may not impose significant risk of subclinical coronary atherosclerosis in those who never used cocaine, whereas the adverse effect of long-term ART use on subclinical coronary atherosclerosis is very apparent in chronic cocaine users.....Our data suggest that cocaine use is ...... a risk factor for subclinical atherosclerosis in HIV-infected persons, especially in those with long-term exposure to ART.
........More-detailed analyses revealed that duration of ART use in HIV infected modified the overall association between HIV infection and subclinical coronary atherosclerosis-compared to those without HIV infection, those who were HIV infected and ART naïve were at significantly lower risk for the presence of any coronary stenosis, noncalcified plaque, and subclinical CAD (Table 3, I. comparing those HIV infected ART naïve with HIV uninfected); however, those who were HIV infected and had used ART ≥36 months were at significantly higher risk for the presence of any coronary stenosis (Table 3, III. comparing those HIV infected and ART use ≥36 months with HIV uninfected). These results may partly explain why no significant overall association was found between HIV infection and the presence of subclinical coronary atherosclerosis. The diametrically opposite effects of HIV infection for those who were ART naïve and those who had used ART for ≥36 months cancelled one another out, yielding an overall nonsignificant association between subclinical coronary atherosclerosis and HIV infection in the study population....It is critically important to emphasize that despite the fact that an overall nonsignificant association between HIV infection and subclinical coronary atherosclerosis was observed, the findings of this study should not be interpreted as evidence against existence of the adverse cardiovascular consequences of HIV infection"
[from Jules: first, this study looked at cocaine users vs non-users BUT the definition of non users was not having used in the past 5 years meaning that if participants had previously used cocaine 5 or more years ago the affects on CVD could interfere in the outcome of this study. The comparator s=group should be people who NEVER used cocaine ever.]
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