2017 CROI: 15 February Coverage PDF Print E-mail
Written by Alain Lafeuillade   
Thursday, 16 February 2017 11:15

2017 CROI: 15 February Coverage

2017_CROI_DAY_3Christina Psomas, MD, PhD, is our "grand reporter" at the 2017 CROI taking place in Seattle this week.

In this article you will find her summary of the third day of the conference

Enjoy reading it !








Dr Shannon L. Hader (58), a Public Health leader from CDC, Atlanta, inaugurated the Wednesday Plenary Session (PL-2) talking about HIV in youth: shifting demographic patterns, complexity to interrupting HIV transmission, complexity to preventing an epidemic development among youth. Growth projection between 2017 and 2050 testify an absolute increase especially in Africa's young adult population aged 15-24. Yet even with more tools in fighting or preventing HIV than ever before (risk avoidance, voluntary medical male circumcision, condom distribution and use, PrEP, early diagnosis and ARV treatment, TASP) many structural factors may explain persistent HIV risk behaviors: urbanization (highest in the developing world), education, economic growth and employment, contexts of vulnerability including persistent violence. "PEPFAR DREAMS" initiative mobilizes communities to reduce infection among women. Preventing epidemic among youth implicates to act fast, work together, engage young people and foster bold leadership.

Dr Barney S. Graham from NIAID/VRC/NIH, Bethesda (59), described antiviral vaccine development from A (AIDS) to Z (Zika). The problem of emerging viral diseases teaches us that traditional health approaches (licensed vaccines or antibiotics, passive surveillance, contact tracing and quarantine) are inadequate to anticipate or to manage new microbial threats. Most emerging infectious diseases are caused by viruses and are either zoonotic (75%) or vector borne. They are more frequently discovered in developed countries, but their event risk is higher in developing countries. AIDS began as a zoonotic transmission that circulated in humans for decades before evolving to the current pandemic. Research and Development infrastructure currently offers partners for advanced vaccine development. Applying new technology options (structural biology, protein design, high throughput sequencing, advanced imaging, systems biology, new understanding of immunology) should generate the tools to engineer better vaccines and be prepared for their rapid deployment in order to face future pandemics.

Dr Benjamin B. Gelman from Galveston (68) presented his study regarding the latent pool of HIV DNA in deep body compartments such as the central nervous system (CNS). In 29 decedent HIV-infected patients he mapped total and integrated gag-pol HIV DNA and RNA in brain using PCR and the Alu-gag assay. Patterns of brain compartmentalization were analyzed according to systemic viral suppression.

The total size of the latent pools in the brain was nearly always highest in white matter, because the white matter compartment contains the most mass. The intensity of systemic viral replication does not influence HIV reservoir size in brain, PBMCs, gastrointestinal tissue, spleen and kidney. On the contrary, strong systemic viral replication does influence HIV reservoir size in muscle, heart, fat, bone marrow and lungs. But CNS compartmentalization patterns deviated widely with regards to the intensity of systemic viral suppression: the more intensely suppressed brain specimens were, the higher HIV DNA was in white matter (p< 0,02) without a difference in total brain pool size.

Dr Jaclyn Mallard from Chestnut Hill (69), studied 16 SIVmac251-infected and 2 uninfected rhesus macaques in order to assess presence of T cells or monocyte/macrophage (Mo/Mf) in the cerebrospinal fluid (CSF), choroid plexus (CP), and central nervous system (CNS) parenchyma. Phylogeographic analysis of SIV sequences was used to assess compartmentalization of virus in order to determine sources of viral reservoirs.

She detected Mo/Mf but not T cells in CP from SIVE animals. In SIVE animals, CP and CNS parenchymal sequences were highly compartmentalized, which means that these tissues are sources of CNS viral reservoirs. CSF is not a viral reservoir because of the dispersed phylogeny of CSF viral sequences among peripheral and CNS sequences.


Dr Sandhya Vasan from Thailand (70), studied biomarkers of immune activation (Luminex) and CNS cellular infiltrate (Immunohistochemistry or IHC) in SHIV-infected macaques. SHIV RNA was detected in CSF of animals with the highest plasma viral load. Early SHIV infection was characterized by a T-cell mediated process with mild CD3+ infiltrate in the brain parenchyma, increased CD4+ T cells in the meninges, but no increase in parenchyma or meningeal CD68+ macrophages.


Dr Rujipas Sirijatuphat from Bangkok (71) used targeted deep sequencing to study paired plasma and CSF samples of 13 ART-naïve acutely HIV-infected RV254/SEARCH010 participants (median: 22 days post estimated infection), in order to evaluate the compartmentalization of HIV-1 in the CSF. A low level of polymorphisms was detected in plasma and CSF (median 0.8%; range 0.5-10%), while 5 participants were infected with multiple transmitted/founder (T/F) viruses. 12/13 participants did not show significant evidence of compartmentalization between CSF and plasma. No major drug resistance was found either. Thus, this study shows evidence that HIV-1 compartmentalization can occur as early as acute infection, within days of exposure, even if this phenomenon is rather uncommon. Further studies are needed to explain determinants of initial sequestration/enrichment of T/F variants in the CNS compartment, as well as potential long-term implications for persistence of HIV-1 reservoirs and neurological impairment in HIV.


Dr Leah T. Le from New Haven (72) presented a retrospective longitudinal analysis of the PISCES cohort in San Francisco, assessing the trajectory of blood CD4/CD8 ratio over time as compared to neuropsychological testing performance during primary HIV infection (PHI) (<12 months after HIV infection). In multivariate analysis of a total of 550 observations (109 participants of a median age of 36 years), change in CD4/CD8 ratio was the sole parameter that was independently associated with NPZ4 score and more specifically with change in processing speed in early HIV infection. Change in CD4/CD8 ratio was inversely correlated with delayed treatment time, as well as change in CSF neurofilament light chain in early infection prior to ART. Other factors independently associated with CD4/CD8 ratio were age at baseline, duration of infection at baseline, CD4/CD8 ratio at baseline and ART. The CD4/CD8 ratio may thus be used as a marker of neurocognitive impairment even during early infection.


Dr Sarah Beth Joseph from Chapel Hill (73) described causes of asymptomatic HIV-1 CSF escape (detectable HIV RNA in the CSF of participants that are well suppressed systemically and lack overt neurological symptoms) and its consequences in terms of neuronal damage. In a cross-sectional analysis of the THINC cohort (103 participants enrolled at Yale, UNC and UCSF), 6,6% presented asymptomatic CSF escape defined by CSF VL > 40 cp/ml while plasma VL < 100 cp/ml and CSF VL > plasma VL, which is a rather uncommon phenomenon. Overall, this state of escape was not associated with elevated levels of neopterin or neurofilament light chain (NFL) (no evidence of neuronal damage/inflammation). The majority of participants with CSF escape had low pleocytosis and neopterin, often accompanying escape virus population that was genetically distinct from the population present in the plasma pre-therapy, that was R5 Macrophage-tropic and drug resistant. The long-term consequences of such a population and the ability of such a population to reseed the periphery are unknown. This example of persistent CSF escape is a clear example of an active (not latent) reservoir. A subset of only 2 participants with CSF escape had high levels of CSF pleocytosis and neopterin; this transient CSF escape population was extremely homogeneous, X4 T-cell tropic and drug sensitive. It was likely produced by an infected T cell that migrated into the CNS in the setting of neuroinflammation, rather than by a CNS reservoir.



Dr Scott Letendre from San Diego (74), evaluated molecular mechanisms associated with neurocognitive (NC) performance of HIV+ adults, namely single nucleotide polymorphisms (SNPs) in the EIF2AK3 gene. 1047 participants from CHARTER's Genome Wide Association Study (GWAS) had a gene assessment for the presence or absence of 3 SNPs in the EIF2AK3, as well as evaluation of their neurocognitive performance using the Global deficit Score (GDS) and the Global NCI. He concluded that variations in the EIF2AK3 gene were associated with neurocognitive performance.


Dr Dominique Costagliola from Paris (75), presented Microbreak 1 study, that was a sectional study to estimate the prevalence of cerebral small vessel disease (CSVD) detected by MRI in persons living with controlled HIV infection. 456 PLWHIV and 154 uninfected controls were analyzed by means of MRI. The prevalence of CSVD was 52% in a well controlled group of PLWHIV over 50 years of age, with an ORa of 2.3 (1.5-3.6) compared with HIV-uninfected controls. The difference regarding severe CSVD, was not significant between the two groups. Classical risk factors associated with CSVD were age and hypertension. The only HIV related risk factor associated with CSVD was a CD4 nadir cell count < 200/mm3.


The S-5 Symposium treating "Hepatitis and Liver" related matters was chaired by Dr Marion G. Peters and Dr Massimo Puoti.

Dr Patrick Kennedy from London (96) did an outstanding presentation on hepatitis B progress and prospects in hepatitis B virus care. Chronic Hepatitis B (CHB) is currently divided by its inflammatory status in non/low inflammatory CHB and inflammatory CHB. Current therapies are non-curative, and even if long-term suppression is achieved, sustained immune control following treatment cessation is limited. In keeping with this, achieving HBsAg loss (or functional cure) in CHB is now known to be dependent not only on direct antiviral therapies, but also on global immune restoration. Even if a multitude of novel agents (TAF, entry inhibitors, HBV Capsid Assembly Modulators, RNAi, Core Protein/Capsid Inhibitors, TLR7 agonists) enter various phases of clinical trials, progress towards HBV cure will also implicate better utilization of current therapies through combination and/or sequential strategies. Major challenges of novel therapeutic approaches include degradation of the cccDNA reservoir without generating excess liver damage.


Dr Mindie H. Nguyen from Palo Alto (97) described management of CHB infection during pregnancy. Women of childbearing age with CHB are more likely to have high HBV viral load and be HBeAg+, which can lead to failures of immunoprophylaxis to newborns (up to 30%). Women with cirrhosis should receive antiviral therapy before and during pregnancy, while women without advanced disease can generally wait until after pregnancy. The American Association for the Study of Liver Diseases (AASLD) guidelines recommend antiviral therapy for pregnant women with HBV DNA > 200,000 IU/ml, even in the absence of clinical symptoms, in order to reduce mother-to-child-transmission (MTCT), as well as monitoring for ALT flares more closely when antiviral therapy is discontinued. In a recent randomized controlled trial initiation of antiviral therapy at 30-week gestation in combination with birth-dose HBV immunoglobulin and vaccination followed by completion of the 3-dose vaccine series has been shown to be safe and effective in preventing MTCT in highly viremic women. No consensus exists on the management of women with HBV DNA < 200,000 IU/mL, with active hepatic inflammation or advanced fibrosis, or who become pregnant while on therapy.


Dr John W. Ward from Atlanta (98) commented on the recent strategy of the World Health Organization for global elimination of hepatitis C virus (HCV) by 2030 as a major Public Health Threat. Improvements in HCV testing, care and cure cascade could reduce HCV transmission by 90% and HCV-related mortality by 65%. Strategies that expand access to HCV testing include provider education, adoption of clinical decision tools, training of primary-care clinicians and reflex RNA testing. Patient navigation services help persons begin and remain in care. Creative solutions such as affordable HCV therapies are needed for universal access to HCV treatment. Harm reduction services can enhance prevention among PWID. Targeted interventions to incarcerated or other marginalized populations are necessary in order to achieve elimination goals. The priorities for elimination of HCV transmission include improved detection in target settings, investigation of transmission networks, evidence based interventions of prevention and treatment, as well as improvement of implementation of prevention strategies.


Dr Rohit Loomba from La Jolla (99) described epidemiology and subtypes of nonalcoholic fatty liver disease (NAFLD) that is commonly associated with obesity and metabolic syndrome. Nonalcoholic SteatoHepatitis (NASH) is the progressive form of NAFLD that can lead to progressive fibrosis, cirrhosis and hepatocellular carcinoma. NASH is typically associated with steatosis, lobular inflammation, ballooning and peri-sinusoidal fibrosis. Causes of secondary NASH include hepatitis C infection, medications, lipodystrophy or HIV. Novel advanced MR-based methods suggest efficiency of localization and quantification of fat by MRI-PDFF, as well as efficiency of detection and quantification of fibrosis by MRE (MR Elastography) using a "stiffness" cutoff of 3,63 kPa. A head to head prospective comparison among patients of the UCSD NAFLD cohort demonstrated a significantly better diagnosis of fibrosis (≥ stage 1) of MRE compared to TE (Transient Elastography).


Key words: HIV, HIV cure, HIV reservoirs
Last Updated on Tuesday, 07 March 2017 07:31


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