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Brain in Older HIV+ - We Do Not Understand the Brain in Older HIV+
  .....Hiv gets into the brain -within days HIV enters the brain, there is CSF RNA and inflammation is detectable.....'HIV Affects Brain Immediately After Infection with HIV RNA in the CSF & Inflammation & Brain Injury Continues Unfolding During Chronic Infection
from Jules: With advancing older ages of HIV+ we do not study nor understand in real time what the brain & cognitive dysfunction is doing to the collective of older patients. HIV > 65 are experiencing double the number of comorbidities compared to HIV-negatives.......50% in Wash Dc of older HIV+ are not getting treated for comorbidities......We do not have a good real time reporting of large numbers of patients & what they exactly are experiencing in their 60s & older. It is not enough to report 5 years later that 5 years ago this percentage of patients had bone disease, we need reporting on the real life daily living & mental & physical experiences of patients & how they are experiencing aging. i hear from some key doctors - ' oh, its not a big deal in my practice - AND then I hear from other doctors here in NY in particular the devastating affects on patients of multiple comorbidities & polyphamacy and trouble walking, falls & fractures. Yet the NIH, The White House, the OAR, NAIAD have not dedicated a lot of resources to discussing this problem. Yes the ACTG is researching new drugs for anti-inflammation & you read about these drugs & the research here :http://www.natap.org/2016/AGE/AGE_36.htm
BUT are they really stretching themselves in what they research or are they looking at drugs that are easy & more likely to get funding rather than looking for drugs that might really help?? Regardless, solving inflammation is not the point of my discussion here, rather its the leadership & most advocates being unwilling to recognize & discuss the impact of aging in real life & how we could do more & design programs to help both patients & doctors understand - support services for patients, education for doctors & patients, better care for comorbido=itues -
[We know 50% of HIV+ are over 50 years old now & we know soon 50% will be over 60 years old. We here reports from studies of patients over 50 & more after 60 years old are experiencing harshly increasedGeriatric Syndromes-which limits independent living activitieslike doing simple tasks: using transportation, going to doctor visits, shopping - and affects children with HIV too -CROI: Premature Aging and Immune Senescence in HIV-1-Infected Children - (03/16/15) - comorbidities can affect blacks more than whites:http://natap.org/2015/CROI/croi_158.htm]
Efavirenz-Induced Nitric Oxide Affects Mitochondrial Function in Glial Cells - (12/05/16)
Depression and Social Isolation Mediate Effect of HIV Stigma on Women's ART Adherence - (02/26/16)
CROI: Neurotoxicity Screening of An...tiretroviral Drugs With Human iPSC-Derived Neurons
CROI: Frailty is associated with NNRTI-based Initial ART and Modifiable Risks in ACTG 5322 - (02/29/16)
brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro......https://www.ncbi.nlm.nih.gov/pmc/articles/PMC239813/
'Accelerated ageing' and 'frailty phenotypes' have been reported to occur prematurely in treated HIV disease, with recent work describing a relationship between antiretroviral drug exposure and markers of cellular ageing such as telomerase length [9-11]. The increasing burden of cognitive impairment associated with advanced age, which may be accelerated by chronic antiretroviral toxicity, represents another indirect pathogenic mechanism......http://www.natap.org/2014/HIV/012315_03.htm Several laboratory models have suggested CNS neurotoxicity to be present for many of the antiretroviral agents in current clinical use. In a key study by Robertson et al.[19], neuronal cell cultures from sacrificed rat brains were exposed to several antiretroviral agents at varying concentrations. Extensive cell death was seen only at the highest concentrations of some drugs (notably efavirenz); however, moderate damage, manifested by dendritic beading and loss of dendrites, was also observed. Of concern, for some antiretroviral agents, these were at concentrations that would be expected using standard clinical doses.
NRTI-exposed individuals had an increased frequency of COX-deficient muscle fibres (Fig. 1). The severity of this defect was proportional to the cumulative lifetime NRTI exposure, but not to therapy at the time of biopsy, indicating a possible legacy effect of prior NRTI use. The changes observed were comparable to or even exceeded those reported in healthy elderly adults, despite all participants being aged 50 or under......Direct toxicity to peripheral nerves is a frequent side effect associated with the older nucleoside reverse transcriptase inhibitors (NRTIs), particularly the dideoxy-nucleosides. There is emerging evidence, albeit in mice, that this effect is not limited to the peripheral nerves. Chronic administration of NRTIs was associated with a reduction in mtDNA in murine cerebral cortex neurons [14].
data from a study of acutely infected patients in Thailand and he found within days HIV enters the brain, there is CSF RNA and inflammation is detectable.....'HIV Affects Brain Immediately After Infection with HIV RNA in the CSF & Inflammation & Brain Injury Continues Unfolding During Chronic Infection & There is a Need for Routine Monitoring'.....http://www.natap.org/2011/CROI/croi_123.htm
These data provide evidence that neuroinflammation or glial dysfunction occurs in the earliest stages after exposure to HIV and are normalized by HAART.....The patients in this cohort have been infected for less than a month. This is not really early (primary) infection but super early acute infection, meaning there is likely not enough time for the brain to have substantial injury.


ART in Acute Infection, Inflammation/Activation "Largely Disappear".......http://natap.org/2015/CROI/croi_162.htm
Inflammation Persists Despite Early ART in Acute HIV.....http://www.natap.org/2015/CROI/croi_154.htm
Conclusions: Enterocyte turnover increases after initiation of ART during acute infection and persists into chronic infection. Biomarkers of inflammation, microbial translocation and fibrosis decrease, but remain elevated compared to HIV- controls with the exception of D-dimer. Together, these data suggest that the inflammatory damage caused by HIV may not be completely prevented by starting ART during acute HIV infection.
This was a followup from CROI 2014 where the authors reported: Biomarkers of inflammation, coagulation and fibrosis are elevated in AHI (acute HIV) before seroconversion. The temporal course of these biomarkers suggests that peak viral burden and inflammation trigger a pro-thrombotic and pro-fibrotic response. During acute infection you can see (Figures 2 & 3 below) inflammation markers increased but lower in earliest stage (4) of acute infection and increased markers for microbial translocation (damaged gut).

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