2016 CROI Coverage: Thursday 25 PDF Print E-mail
Written by Christina Psomas   
Thursday, 25 February 2016 18:41

2016 CROI Coverage: Thursday 25 February

FinalDayCROILast day of CROI, last plenary session but everybody's still motivated in sunny Boston!!!

Christina Psomas, MD, PhD has followed the meeting since its first day.

Here is the last day scientific report.

Last day of CROI, last plenary session but everybody's still motivated in sunny Boston!!....


ParticipantsEric Rubin began the plenary talking about Tuberculosis (TB) that is the leading infectious cause of death in the world, and the leading killer of people with HIV infection. The main problem with this disease is the lack of ability to measure the amount of disease, as well as the difficulty to predict the risk of getting ill on an individual basis, because dormancy during clinically unapparent infection does not reflect bacterial load and risk of developing active TB. Problems that we encounter in the context of TB treatment are penetration of drugs in TB lesions, as well as phenotypically resistant bacteria. Three treatment-shortening trials (STAND, TBTC Study 31, Nix-TB) are currently enrolling, using novel molecules on top of existing regimens, while use of newer molecules on a large population-basis are limited by the high rates of toxicity.

 

John Brooks analyzed the HIV outbreak in Scott County, Indiana, among persons who injected drugs. While HIV infections attributable to injection drug use in the US have declined steadily over the last 10 years and accounted for 6% of all diagnosed infections in 2014, in early 2015, public health workers serving a small rural Indiana community (adult population approximately 3,100) detected an outbreak of HIV infections within a network of persons who injected drugs. Controlling the outbreak demanded an intensive coordinated response by county, state and federal partners working closely with the community and other stakeholders. Fueled by the growing national epidemic of opioid drug abuse, injection drug use is spreading among populations not previously considered to be at high risk of HIV infection.


Xavier Alvarez opened the Session O-12 of Oral Abstracts, describing a very original technique of following the routes of macrophage cells out of the brain and the rest of the CNS. This technique used cellular (Super Paramagnetic Iron Oxide Nano particles or SPIONs) and fluid tracers (Dextran Red) detected by fluorescence after extensive tissue collections to monitor the exit of cells, a technique that could be used in the future to monitor reservoir cells of the brain, as well as to monitor effects of ART in the brain.


Xiang Li presented his results concerning CSF lymphocyte and monocyte activation and trafficking during untreated primary HIV infection. He described a rapid increase of CSF T-cell activation suggesting an early traffic into the CNS in early infection. He observed load or CSF T-cell activation (CD38+ HLA-DR+).

 

Michelli Faria de Oliveira argued persistence of compartmentalized HIV DNA populations in CSF despite suppressive ART. Using paired blood and CSF samples from 16 treated HIV-infected individuals she showed that the early ART group (≤ 4 months) displayed significantly lower levels of some inflammation markers (IL-6, TNF-alpha) than the late ART group (> 14 months), but no difference in terms of HIV DNA levels and compartmentalization of the CNS DNA reservoir.

 

David Samuels presented results of a study performed by the CHARTER study group. They measured mitochondrial DNA copy number (mtDNA) in the PBMCs of HIV+ patients (cellular mtDNA), as well as cell free mtDNA in CSF and found that these parameters are significantly lower under ART but only the higher whole blood mtDNA copy number was significantly associated with worse cognitive outcomes.


Shibani Mukerji from Massachussetts General Hospital investigated the impact of lipid profiles and ApoE E4 genotype on cognitive decline in ART-adherent HIV+ adults between ages 50-65 years old, presenting with 69.6% of viral suppression. She found that dyslipidemia and ApoE genotype were associated with faster rates of cognitive decline, which could open pathways to preventive strategies of midlife cognitive impairment in HIV+ patients.


Ned Sacktor presented a double-blind placebo-controlled trial concerning the use of paroxetine and fluconazole therapy for HAND, which are molecules that have already proven neuroprotection in SIV model. In intent-to-treat analysis, the benefit of paroxetine was partial in terms of global neurocognitive improvement or CSF markers of immune activation and neuronal injury. She was not associated with decreases in CSF lipid markers of oxidative stress. The use of fluconazole did not translate to neurocognitive benefit.

 

Kevin Robertson showed results of the ACTG A5303 concerning use of MVC and TDF in initial ART and effects on neurocognitive impairment. He concluded that DRV/r + FTC + MVC or TDF are equivalent first-line regimens in terms of neurocognition evaluated by GDS. InMIND study (ACTG 5324) will soon evaluate the effect of intensification in patients with neurocognitive impairment.

 

Jonathan Underwood displayed results of the COBRA collaboration of European cohort studies concerning relationship of structural brain (MRI scanning with grey matter volume, diffusion tensor imaging) and cognitive abnormalities. He showed evidence of grey matter atrophy and white matter microstructural injury despite fully suppressive ART and in association with poorer cognitive function and markers of immune dysregulation (CD4/CD8 ratio).


CCENTER

The session TD-13 of Themed Discussion opened with Nina Kim on behalf of the CFAR Network of Integrated Clinical System (CNICS). This work determined the incidence and predictors of advanced hepatic fibrosis, defined as FIB-4 index ≥ 3.25, in HIV-infected patients without significant liver disease. In this study, HCV, HBV, alcohol use disorder and diabetes mellitus were significantly associated with progression, while race and sex were not. In addition, CD4 T cell count and HIV viral level were independent risk factors. These findings provide clinical evidence for the role of viral mediated liver injury and suggest that early and effective ART could medicate HIV-associated liver disease progression. 

 

Raphael Mohr showed results of a cross-sectional prospective study that demonstrated statistical associations between liver fibrosis and viral (duration of HIV infection, ART duration, HIV viral load) or metabolic factors (BMI, diabetes mellitus, FIB4) in HIV mono-infected individuals.

Antoine Jacquet described factors associated with liver fibrosis among persons living with HIV in West Africa, namely HBV presence and heavy or even hazardous alcohol use.


Antoine Jacquet described factors associated with liver fibrosis among persons living with HIV in West Africa, namely HBV presence and heavy or even hazardous alcohol use.


Rebecca Krakora analyzed biomarkers associated with liver biopsy-proven NASH in mono-infected HIV adults under suppressive ART and found a more specific association between HIV+NASH and TNFalpha, sCD163, CXCL10 and IL-8.


Janet Lo interestingly presented a 12-month, randomized, placebo-controlled trial of the effect of atorvastatin on hepatosteatosis defined on a non-contrast CT among HIV-infected patients with NAFLD. She concluded that atorvastatin reduced hepatosteatosis amon HIV patients without concurrent changes in BMI or VAT.

 

Marcus Altfield was the first talker of the session S-10 Symposium relative to the Natural Born Killers. He presented his group's work trying to elucidate mechanisms by which NK cells are able to recognize HIV-infected cells. These mechanisms include loss of engagement of inhibitory KIRs, as well as sensing of stress-induced molecules (HLA-F) by activating KIRs. HIV-1 can evade NK cell-mediated immune pressure by selection of sequence mutations within HLA class I presented epitopes, rescuing binding of iKIRs. Thus, his work identifies novel pathways of NK-cell mediated control of viral infections.


Catherine Blish described NK cells' diversity resulting from activating and inhibitory receptors that generate combinatorial single-cell phenotypes. Thus, specific populations of NK cells target cells infected with viruses; immature and transitional NK cells preferentially respond to West Nile virus, NKG2A+ NK cells respond to lytic EBV and HIV. Diverse NK repertoires are associated with terminal differentiation and cytokine production. In a cohort of Kenyan women, NK diversity predicts the risk of HIV-1 acquisition, but confirmatory studies are needed. Consequently, NK cell diversity may not be beneficial to the innate immune system.


Jonathan Karn described how NK cells recognize activating ligands on the surface of target cells but are inhibited by MHC molecules. Their hypothesis is that there may be a window of opportunity after proviral activation when NK cells can target and kill latently infected primary T cells due to MHC downregulation by Nef. When NK cells are cocultured with cells expressing IL-21, they observed dramatic NK cell expansion and enhancement of toxicity against reactivated latently infected primary T cells, as well as their ability to mediate ADCC. This group has identified at least one anti-Env antibody that can strongly mediate ADCC activity and enhance selectivity of killing reactivated HIV-1-infected CD4+ T cells while sparing uninfected cells. Enhancing NK cell activity may represent an important new approach to virus eradication.


Finally, Andrès Finzi closed the CROI 2016 presenting interesting data of his work. His aim is to promote targeting of HIV-infected cells by ADCC. He tested the capacity of rationally-designed CD4-mimetic compounds (CD4mc) to promote the CD4-bound conformation of Env and thereby sensitize HIV-1-infected cells to ADCC. Upon testing a panel of anti-Env antibodies he found that the anti-cluster A class mediated the most robust ADCC response. Altogether, these data suggest that forcing Env to expose highly-conserved epitopes, recognized by antibodies present in the sera of HIV-1-infected individuals, might represent a new approach for HIV eradication strategies.

 

pano-CROI

A very interesting and interactive CROI meeting is now completed, hope to see you again next year in Seattle!!!



Key words: CROI, Christina Psomas, HIV, HIV persistence, ISHEID
Last Updated on Thursday, 10 March 2016 11:45
 

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